[ { "id": "https://authors.library.caltech.edu/records/ch9jq-hc145", "eprint_status": "archive", "datestamp": "2024-01-10 20:00:52", "lastmod": "2024-01-10 20:00:52", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhou-Tingtao", "name": { "family": "Zhou", "given": "Tingtao" }, "orcid": "0000-0002-1766-719X" }, { "id": "Wan-Xuan", "name": { "family": "Wan", "given": "Xuan" }, "orcid": "0000-0002-6165-6340" }, { "id": "Huang-Daniel-Zhengyu", "name": { "family": "Huang", "given": "Daniel Zhengyu" } }, { "id": "Li-Zongyi", "name": { "family": "Li", "given": "Zongyi" }, "orcid": "0000-0003-2081-9665" }, { "id": "Peng-Zhiwei", "name": { "family": "Peng", "given": "Zhiwei" }, "orcid": "0000-0002-9486-2837" }, { "id": "Anandkumar-A", "name": { "family": "Anandkumar", "given": "Anima" }, "orcid": "0000-0002-6974-6797" }, { "id": "Brady-J-F", "name": { "family": "Brady", "given": "John F." }, "orcid": "0000-0001-5817-9128" }, { "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173" }, { "id": "Daraio-C", "name": { "family": "Daraio", "given": "Chiara" }, "orcid": "0000-0001-5296-4440" } ] }, "title": "AI-aided geometric design of anti-infection catheters", "ispublished": "pub", "full_text_status": "public", "keywords": "Multidisciplinary", "note": "
© 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
\n\nThis work was supported by the following: the Donna and Benjamin M. Rosen Bioengineering Center Pilot Research Grant (J.F.B. and C.D.), the Heritage Medical Institute at Caltech (C.D.), and the National Science Foundation, Center to Stream Healthcare in Place (C2SHIP), award no. 2052827 (C.D.). D.Z.H. is supported by the generosity of Eric and Wendy Schmidt by recommendation of the Schmidt Futures program. Z.L. is supported in part by the PIMCO Fellowship and Amazon AI4Science Fellowship. A.A. and P.W.S. are supported by Bren Professorships.
\n\nX.W., T.Z., P.W.S., and C.D. designed experiments. X.W. and T.Z. performed experiments and analyzed data. T.Z. and Z.P. performed simulations. D.Z.H. and Z.L. designed the AI model and performed optimization. A.A. conceptualized and planned the AI framework. T.Z., J.F.B., and C.D. conceived the project. P.W.S. and C.D. supervised the project. All authors discussed the results and contributed to the manuscript writing.
\n\nAll data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Supplementary data for the optimization process are included in the following link: https://data.caltech.edu/records/mdj7m-ajv14.
\n\nCalifornia Institute of Technology (Caltech) has a patent pending related to the discoveries in this manuscript. Patent status: Pending. Name of organization issuing patent: The United States Patent and Trademark Office (USPTO). All authors are inventors. Filing date: 13 March 2023. Serial number: 63/451,788. The authors declare that they have no other competing interests.
", "abstract": "Bacteria can swim upstream in a narrow tube and pose a clinical threat of urinary tract infection to patients implanted with catheters. Coatings and structured surfaces have been proposed to repel bacteria, but no such approach thoroughly addresses the contamination problem in catheters. Here, on the basis of the physical mechanism of upstream swimming, we propose a novel geometric design, optimized by an artificial intelligence model. Using\n Escherichia coli\n , we demonstrate the anti-infection mechanism in microfluidic experiments and evaluate the effectiveness of the design in three-dimensionally printed prototype catheters under clinical flow rates. Our catheter design shows that one to two orders of magnitude improved suppression of bacterial contamination at the upstream end, potentially prolonging the in-dwelling time for catheter use and reducing the overall risk of catheter-associated urinary tract infection.", "date": "2024-01-05", "date_type": "published", "publication": "Science Advances", "volume": "10", "number": "1", "publisher": "American Association for the Advancement of Science", "pagerange": "eadj1741", "issn": "2375-2548", "official_url": "https://authors.library.caltech.edu/records/ch9jq-hc145", "funders": { "items": [ { "grant_number": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "grant_number": "Heritage Medical Research Institute" }, { "grant_number": "CNS-2052827" }, {}, { "grant_number": "Amazon AI4Science Fellowship" }, { "grant_number": "Bren Professor of Computing and Mathematical Sciences" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" }, { "id": "Rosen-Bioengineering-Center" }, { "id": "Heritage-Medical-Research-Institute" } ] }, "doi": "10.1126/sciadv.adj1741", "pmcid": "PMC10776022", "primary_object": { "basename": "sciadv.adj1741.pdf", "url": "https://authors.library.caltech.edu/records/ch9jq-hc145/files/sciadv.adj1741.pdf" }, "related_objects": [ { "basename": "sciadv.adj1741_movies_s1_to_s3.zip", "url": "https://authors.library.caltech.edu/records/ch9jq-hc145/files/sciadv.adj1741_movies_s1_to_s3.zip" }, { "basename": "sciadv.adj1741_sm.pdf", "url": "https://authors.library.caltech.edu/records/ch9jq-hc145/files/sciadv.adj1741_sm.pdf" } ], "pub_year": "2024", "author_list": "Zhou, Tingtao; Wan, Xuan; et el." }, { "id": "https://authors.library.caltech.edu/records/dt31x-1gg04", "eprint_status": "archive", "datestamp": "2024-01-09 20:16:06", "lastmod": "2024-01-09 20:16:06", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "name": { "family": "Qin", "given": "Zi-Yang" }, "orcid": "0000-0001-7356-6927" }, { "name": { "family": "Gao", "given": "Shilong" }, "orcid": "0000-0003-2808-6283" }, { "name": { "family": "Zou", "given": "Yike" }, "orcid": "0000-0003-4380-7827" }, { "name": { "family": "Liu", "given": "Zhen" }, "orcid": "0000-0002-1119-0693" }, { "name": { "family": "Wang", "given": "James B." }, "orcid": "0000-0003-4085-3035" }, { "name": { "family": "Houk", "given": "Kendall N." }, "orcid": "0000-0002-8387-5261" }, { "id": "Arnold-F-H", "name": { "family": "Arnold", "given": "Frances H." }, "orcid": "0000-0002-4027-364X" } ] }, "title": "Biocatalytic Construction of Chiral Pyrrolidines and Indolines via Intramolecular C(sp\u00b3)\u2013H Amination", "ispublished": "pub", "full_text_status": "public", "keywords": "General Chemical Engineering; General Chemistry", "note": "\u00a9 2023 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0.
\n\nThis work is supported by the National Science Foundation Division of Molecular and Cellular Biosciences (Grant 2016137 to F.H.A.) and the National Science Foundation Division of Chemistry (Grant 1764328 to K.N.H.). Anton 2 computeri time was provided by the Pittsburgh Supercomputing Center (PSC) through support by the National Institutes of Health (Grant R01GM116961). Z.-Y.Q. thanks the funding support from the Biotechnology Leadership Program (BLP) in the Donna and Benjamin M. Rosen Bioengineering Center of the Division of Chemistry and Chemical Engineering at Caltech. We thank Dr. Runze Mao, Dr. Edwin Alfonzo, Dr. Cooper Jamieson, and Dr. Sabine Brinkmann-Chen for helpful discussions and comments on the manuscript. We thank Dr. Scott C. Virgil for his assistance with chiral-phase HPLC experiments. We further thank Dr. Mona Shahgholi for HRMS analysis.
\n\nZ.Y.Q. and S.L.G. contributed equally.
\n\nThe authors declare no competing financial interest.
", "abstract": "Nature harnesses exquisite enzymatic cascades to construct N-heterocycles and further uses these building blocks to assemble the molecules of life. Here we report an enzymatic platform to construct important chiral N-heterocyclic products, pyrrolidines and indolines, via abiological intramolecular C(sp\u00b3)\u2013H amination of organic azides. Directed evolution of cytochrome P411 (a P450 enzyme with serine as the heme-ligating residue) yielded variant P411-PYS-5149, capable of catalyzing the insertion of alkyl nitrene into C(sp\u00b3)\u2013H bonds to build pyrrolidine derivatives with good enantioselectivity and catalytic efficiency. Further evolution of activity on aryl azide substrates yielded variant P411-INS-5151 that catalyzes intramolecular C(sp\u00b3)\u2013H amination to afford chiral indolines. In addition, we show that these enzymatic aminations can be coupled with a P411-based carbene transferase or a tryptophan synthase to generate an \u03b1-amino lactone or a noncanonical amino acid, respectively, underscoring the power of new-to-nature biocatalysis in complexity-building chemical synthesis.
", "date": "2023-12-27", "date_type": "published", "publication": "ACS Central Science", "volume": "9", "number": "12", "publisher": "American Chemical Society", "pagerange": "2333-2338", "issn": "2374-7943", "official_url": "https://authors.library.caltech.edu/records/dt31x-1gg04", "funders": { "items": [ { "grant_number": "MCB-2016137" }, { "grant_number": "CHE-1764328" }, { "grant_number": "R01GM116961" }, { "grant_number": "Donna and Benjamin M. Rosen Bioengineering Center" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1021/acscentsci.3c00516", "pmcid": "PMC10755850", "primary_object": { "basename": "oc3c00516_si_001.pdf", "url": "https://authors.library.caltech.edu/records/dt31x-1gg04/files/oc3c00516_si_001.pdf" }, "related_objects": [ { "basename": "oc3c00516.pdf", "url": "https://authors.library.caltech.edu/records/dt31x-1gg04/files/oc3c00516.pdf" } ], "pub_year": "2023", "author_list": "Qin, Zi-Yang; Gao, Shilong; et el." }, { "id": "https://authors.library.caltech.edu/records/7w289-s1c34", "eprint_status": "archive", "datestamp": "2023-12-18 18:50:42", "lastmod": "2023-12-18 18:50:42", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ling-Bill", "name": { "family": "Ling", "given": "Bill" }, "orcid": "0000-0002-1276-7204" }, { "id": "Ko-Jeong-Hoon", "name": { "family": "Ko", "given": "Jeong Hoon" }, "orcid": "0000-0003-2000-3789" }, { "id": "Stordy-Benjamin", "name": { "family": "Stordy", "given": "Benjamin" }, "orcid": "0000-0002-1096-3287" }, { "id": "Zhang-Yuwei", "name": { "family": "Zhang", "given": "Yuwei" } }, { "id": "Didden-Tighe-F", "name": { "family": "Didden", "given": "Tighe F." } }, { "id": "Malounda-Dina", "name": { "family": "Malounda", "given": "Dina" }, "orcid": "0000-0001-7086-9877" }, { "id": "Swift-Margaret-B", "name": { "family": "Swift", "given": "Margaret B." }, "orcid": "0000-0001-9610-0687" }, { "id": "Chan-Warren-C-W", "name": { "family": "Chan", "given": "Warren C. W." }, "orcid": "0000-0001-5435-4785" }, { "id": "Shapiro-M-G", "name": { "family": "Shapiro", "given": "Mikhail G." }, "orcid": "0000-0002-0291-4215" } ] }, "title": "Gas Vesicle\u2013Blood Interactions Enhance Ultrasound Imaging Contrast", "ispublished": "pub", "full_text_status": "public", "keywords": "Mechanical Engineering; Condensed Matter Physics; General Materials Science; General Chemistry; Bioengineering", "note": "\u00a9 2023 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0.
\n\nThe authors thank Prof. Bob Grubbs, Prof. Mark E. Davis, and Dr. Di Wu for helpful discussions; Dr. Hojin Kim for help with the aqueous SEC polymer characterization; Justin Lee for assistance with flow cytometry; Dr. Mona Shahgoli for assistance with small molecule mass spectrometry; the Caltech Cryo-EM Center for assistance with TEM; the Caltech CCE Multiuser Mass Spectrometry Lab for instrumentation to characterize small molecules and GVs; and Dr. Craig Simpson and Dr. Leanne Wynbenga-Groot, The Hospital for Sick Children, Toronto, Canada, for assistance with mass spectrometry for proteomic analysis. This research was supported by the National Institutes of Health (R01-EB018975 to M.G.S.) and the Rosen Bioengineering Center Pilot Grant. W.C.W.C. acknowledges the Canadian Institute of Health Research Grants FDN159932 and MOP-1301431, NMIN Network 2019-T3-01 and Canadian Research Chairs Program Grant 950-223824. J.H.K. was supported by the Kavli Nanoscience Institute Prize Postdoctoral Fellowship at the California Institute of Technology. B.L. was supported by the NIH/NRSA Pre-Doctoral Training Grant (T32GM07616) and the Caltech Center for Environmental and Microbial Interactions. B.S. thanks the Doctoral Completion Award. M.G.S. is a Howard Hughes Medical Institute Investigator.
\n\nB.L. and J.H.K. contributed equally to this work. B.L, J.H.K., and M.G.S. conceptualized the research. B.L. performed the in vivo imaging experiments with assistance from M.B.S. J.H.K. designed polymer synthesis and gas vesicle functionalization reactions with assistance from T.F.D. J.H.K. and B.L. characterized the functionalized gas vesicles. B.L. performed the erythrocyte modeling and incubation experiments. B.S. and Y.Z. performed LC-MS/MS experiments and analyzed the data. D.M. prepared gas vesicles for experiments. All authors contributed to editing and revising the manuscript. M.G.S. and W.C.W.C. supervised the research.
\n\nThe authors declare no competing financial interest.
", "abstract": "Gas vesicles (GVs) are genetically encoded, air-filled protein nanostructures of broad interest for biomedical research and clinical applications, acting as imaging and therapeutic agents for ultrasound, magnetic resonance, and optical techniques. However, the biomedical applications of GVs as systemically injectable nanomaterials have been hindered by a lack of understanding of GVs' interactions with blood components, which can significantly impact in vivo behavior. Here, we investigate the dynamics of GVs in the bloodstream using a combination of ultrasound and optical imaging, surface functionalization, flow cytometry, and mass spectrometry. We find that erythrocytes and serum proteins bind to GVs and shape their acoustic response, circulation time, and immunogenicity. We show that by modifying the GV surface we can alter these interactions and thereby modify GVs' in vivo performance. These results provide critical insights for the development of GVs as agents for nanomedicine.
", "date": "2023-12-13", "date_type": "published", "publication": "Nano Letters", "volume": "23", "number": "33", "publisher": "American Chemical Society", "pagerange": "10748-10757", "issn": "1530-6984", "official_url": "https://authors.library.caltech.edu/records/7w289-s1c34", "funders": { "items": [ { "grant_number": "R01-EB018975" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center, California Institute of Technology" }, { "grant_number": "FDN159932" }, { "grant_number": "MOP-1301431" }, { "agency": "NanoMedicines Innovation Network", "grant_number": "2019-T3-01" }, { "grant_number": "950-223824" }, { "agency": "Kavli Nanoscience Institute, California Institute of Technology" }, { "grant_number": "T32GM07616" }, { "agency": "Center for Environmental Microbial Interactions, California Institute of Technology" }, {}, {} ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" }, { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Kavli-Nanoscience-Institute" } ] }, "doi": "10.1021/acs.nanolett.3c02780", "pmcid": "PMC10722532", "primary_object": { "basename": "nl3c02780.pdf", "url": "https://authors.library.caltech.edu/records/7w289-s1c34/files/nl3c02780.pdf" }, "pub_year": "2023", "author_list": "Ling, Bill; Ko, Jeong Hoon; et el." }, { "id": "https://authors.library.caltech.edu/records/m6t2z-6m909", "eprint_status": "archive", "datestamp": "2023-12-13 19:10:12", "lastmod": "2023-12-18 16:43:30", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ling-Bill", "name": { "family": "Ling", "given": "Bill" }, "orcid": "0000-0002-1276-7204" }, { "id": "Ko-Jeong-Hoon", "name": { "family": "Ko", "given": "Jeong Hoon" }, "orcid": "0000-0003-2000-3789" }, { "id": "Stordy-Benjamin", "name": { "family": "Stordy", "given": "Benjamin" }, "orcid": "0000-0002-1096-3287" }, { "id": "Zhang-Yuwei", "name": { "family": "Zhang", "given": "Yuwei" } }, { "id": "Didden-Tighe-F", "name": { "family": "Didden", "given": "Tighe F." } }, { "id": "Malounda-Dina", "name": { "family": "Malounda", "given": "Dina" }, "orcid": "0000-0001-7086-9877" }, { "id": "Swift-Margaret-B", "name": { "family": "Swift", "given": "Margaret B." }, "orcid": "0000-0001-9610-0687" }, { "id": "Chan-Warren-C-W", "name": { "family": "Chan", "given": "Warren C. W." }, "orcid": "0000-0001-5435-4785" }, { "id": "Shapiro-M-G", "name": { "family": "Shapiro", "given": "Mikhail G." }, "orcid": "0000-0002-0291-4215" } ] }, "title": "Gas Vesicle\u2013Blood Interactions Enhance Ultrasound Imaging Contrast", "ispublished": "pub", "full_text_status": "public", "keywords": "Mechanical Engineering; Condensed Matter Physics; General Materials Science; General Chemistry; Bioengineering", "note": "\u00a9 2023 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0.
\n\nThe authors thank Prof. Bob Grubbs, Prof. Mark E. Davis, and Dr. Di Wu for helpful discussions; Dr. Hojin Kim for help with the aqueous SEC polymer characterization; Justin Lee for assistance with flow cytometry; Dr. Mona Shahgoli for assistance with small molecule mass spectrometry; the Caltech Cryo-EM Center for assistance with TEM; the Caltech CCE Multiuser Mass Spectrometry Lab for instrumentation to characterize small molecules and GVs; and Dr. Craig Simpson and Dr. Leanne Wynbenga-Groot, The Hospital for Sick Children, Toronto, Canada, for assistance with mass spectrometry for proteomic analysis. This research was supported by the National Institutes of Health (R01-EB018975 to M.G.S.) and the Rosen Bioengineering Center Pilot Grant. W.C.W.C. acknowledges the Canadian Institute of Health Research Grants FDN159932 and MOP-1301431, NMIN Network 2019-T3-01 and Canadian Research Chairs Program Grant 950-223824. J.H.K. was supported by the Kavli Nanoscience Institute Prize Postdoctoral Fellowship at the California Institute of Technology. B.L. was supported by the NIH/NRSA Pre-Doctoral Training Grant (T32GM07616) and the Caltech Center for Environmental and Microbial Interactions. B.S. thanks the Doctoral Completion Award. M.G.S. is a Howard Hughes Medical Institute Investigator.
\n\nB.L. and J.H.K. contributed equally to this work. B.L, J.H.K., and M.G.S. conceptualized the research. B.L. performed the in vivo imaging experiments with assistance from M.B.S. J.H.K. designed polymer synthesis and gas vesicle functionalization reactions with assistance from T.F.D. J.H.K. and B.L. characterized the functionalized gas vesicles. B.L. performed the erythrocyte modeling and incubation experiments. B.S. and Y.Z. performed LC-MS/MS experiments and analyzed the data. D.M. prepared gas vesicles for experiments. All authors contributed to editing and revising the manuscript. M.G.S. and W.C.W.C. supervised the research.
\n\nThe authors declare no competing financial interest.
", "abstract": "Gas vesicles (GVs) are genetically encoded, air-filled protein nanostructures of broad interest for biomedical research and clinical applications, acting as imaging and therapeutic agents for ultrasound, magnetic resonance, and optical techniques. However, the biomedical applications of GVs as systemically injectable nanomaterials have been hindered by a lack of understanding of GVs' interactions with blood components, which can significantly impact in vivo behavior. Here, we investigate the dynamics of GVs in the bloodstream using a combination of ultrasound and optical imaging, surface functionalization, flow cytometry, and mass spectrometry. We find that erythrocytes and serum proteins bind to GVs and shape their acoustic response, circulation time, and immunogenicity. We show that by modifying the GV surface we can alter these interactions and thereby modify GVs' in vivo performance. These results provide critical insights for the development of GVs as agents for nanomedicine.
", "date": "2023-12-13", "date_type": "published", "publication": "Nano Letters", "volume": "23", "number": "33", "publisher": "American Chemical Society", "pagerange": "10748-10757", "issn": "1530-6984", "official_url": "https://authors.library.caltech.edu/records/m6t2z-6m909", "funders": { "items": [ { "grant_number": "R01-EB018975" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center, California Institute of Technology" }, { "grant_number": "FDN159932" }, { "grant_number": "MOP-1301431" }, { "agency": "NanoMedicines Innovation Network", "grant_number": "2019-T3-01" }, { "grant_number": "950-223824" }, { "agency": "Kavli Nanoscience Institute, California Institute of Technology" }, { "grant_number": "T32GM07616" }, { "agency": "Center for Environmental Microbial Interactions, California Institute of Technology" }, {}, {} ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" }, { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Kavli-Nanoscience-Institute" } ] }, "doi": "10.1021/acs.nanolett.3c02780", "pmcid": "PMC10722532", "primary_object": { "basename": "ling-et-al-2023-gas-vesicle-blood-interactions-enhance-ultrasound-imaging-contrast.pdf", "url": "https://authors.library.caltech.edu/records/m6t2z-6m909/files/ling-et-al-2023-gas-vesicle-blood-interactions-enhance-ultrasound-imaging-contrast.pdf" }, "related_objects": [ { "basename": "nl3c02780_si_001.pdf", "url": "https://authors.library.caltech.edu/records/m6t2z-6m909/files/nl3c02780_si_001.pdf" }, { "basename": "nl3c02780_si_002.xlsx", "url": "https://authors.library.caltech.edu/records/m6t2z-6m909/files/nl3c02780_si_002.xlsx" } ], "pub_year": "2023", "author_list": "Ling, Bill; Ko, Jeong Hoon; et el." }, { "id": "https://authors.library.caltech.edu/records/rjrx5-9bm15", "eprint_status": "archive", "datestamp": "2023-10-13 16:53:45", "lastmod": "2024-01-09 22:23:51", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Wu-Woods-Natalie-J", "name": { "family": "Wu-Woods", "given": "Natalie J." }, "orcid": "0000-0001-5070-9091" }, { "id": "Barlow-Jacob-T", "name": { "family": "Barlow", "given": "Jacob T." }, "orcid": "0000-0002-1842-4835" }, { "id": "Trigodet-Florian", "name": { "family": "Trigodet", "given": "Florian" }, "orcid": "0000-0002-4933-2896" }, { "id": "Shaw-Dustin-G", "name": { "family": "Shaw", "given": "Dustin G." }, "orcid": "0000-0003-3961-7588" }, { "id": "Romano-Anna-E", "name": { "family": "Romano", "given": "Anna E." }, "orcid": "0000-0002-7148-0668" }, { "id": "Jabri-Bana", "name": { "family": "Jabri", "given": "Bana" }, "orcid": "0000-0001-7427-4424" }, { "name": { "family": "Eren", "given": "A. Murat" }, "orcid": "0000-0001-9013-4827" }, { "id": "Ismagilov-R-F", "name": { "family": "Ismagilov", "given": "Rustem F." }, "orcid": "0000-0002-3680-4399" } ] }, "title": "Microbial-enrichment method enables high-throughput metagenomic characterization from host-rich samples", "ispublished": "pub", "full_text_status": "public", "keywords": "Cell Biology; Molecular Biology; Biochemistry; Biotechnology", "note": "\u00a9 The Author(s), under exclusive licence to Springer Nature America, Inc. 2023.
\n\nWe acknowledge assistance with animal experiments from Caltech Office of Laboratory Animal Research. We thank M. Ratanapanichkich (California Institute of Technology) for assistance on manual refinement of metagenomic bins and feedback on figure design. We thank A. Carter (California Institute of Technology) for assistance with Quant-seq library preparation, ddPCR measurements and feedback during manuscript preparation. We thank M. Cooper (California Institute of Technology) for identifying appropriate statistical tests, guidance during Quant-seq analysis and feedback on figure design. We thank S. R. Bogatyrev for preliminary investigations, discussions and advice. We thank O. Pradhan (California Institute of Technology) and R. Akana (California Institute of Technology) for advice and feedback during manuscript preparation. We thank B. McDonald (University of Chicago) for providing his expertise and advice on clinical sample collection and processing. We thank A. Wang (University of Chicago) for her assistance in the processing of the human tissue for Figs. 3\u20136. We thank N. Shelby (California Institute of Technology) for contributions to writing and editing this manuscript. This work was funded in part by a grant from the Kenneth Rainin Foundation (grant no. 2018-1207 to R.F.I.), the Army Research Office Multidisciplinary University Research Initiative (grant no. W911NF-17-1-0402 to R.F.I.), the Jacobs Institute for Molecular Engineering for Medicine, a NIH NIDDK grant (no. RC2 DK133947 to R.F.I. and B.J.), a National Science Foundation Graduate Research Fellowship (grant no. DGE\u20101745301 to N.J.W.-W.), and a National Institutes of Health Biotechnology Leadership Pre-doctoral Training Program fellowship from Caltech's Donna and Benjamin M. Rosen Bioengineering Center (grant no. T32GM112592, to J.T.B.), a Helmsley Foundation grant (to F.T.), a NIH NIDDK grant (no. RC2 DK122394, to F.T.), a F30 (grant no. 5F30DK121470, to D.G.S.), a R01 (grant no. DK067180, to B.J.) and the Digestive Diseases Research Core Center grant no. P30 DK42086 at the University of Chicago (to B.J.). The funders had no role in the design of the study, the collection, analysis and interpretation of data, nor in writing the manuscript.
\n\nThese authors contributed equally: Natalie J. Wu-Woods, Jacob T. Barlow.
N.J.W.-W. and J.T.B. conceived and optimized MEM. J.T.B. designed sample collection and analyzed 16S sequencing. D.G.S. codesigned and performed human biopsy collection. N.J.W.-W. and F.T. analyzed shotgun sequencing. A.E.R. performed library preparation. R.F.I. contributed to the design and implementation of the study and to obtaining funding. A.M.E. oversaw the bioinformatic analysis, contributed to the design and implementation of the study and to obtaining funding. B.J. supervised the clinical work, contributed to the design and implementation of the study and to obtaining funding. All authors edited the manuscript. A detailed author contribution statement is available in the Supplementary Information.
\n\nThe datasets generated and analyzed during the current study are available at CaltechDATA, https://doi.org/10.22002/gx69z-wec80. Microbial sequencing data are available at NCBI Accession no. PRJNA991155. Sequencing data from human samples have been host scrubbed using STAT78 sra-human-scrubber (https://github.com/ncbi/sra-human-scrubber) followed by alignment to CHM13 (ref. 79). Source data are provided with this paper.
\n\nThe code used in data processing and analysis is available at CaltechDATA, https://doi.org/10.22002/gx69z-wec80.
\n\nThe work in this paper is the subject of a patent application filed by Caltech (R.F.I., N.J.W.-W., J.T.B. and A.E.R.). The other authors declare no competing interests.
", "abstract": "Host\u2013microbe interactions have been linked to health and disease states through the use of microbial taxonomic profiling, mostly via 16S ribosomal RNA gene sequencing. However, many mechanistic insights remain elusive, in part because studying the genomes of microbes associated with mammalian tissue is difficult due to the high ratio of host to microbial DNA in such samples. Here we describe a microbial-enrichment method (MEM), which we demonstrate on a wide range of sample types, including saliva, stool, intestinal scrapings, and intestinal mucosal biopsies. MEM enabled high-throughput characterization of microbial metagenomes from human intestinal biopsies by reducing host DNA more than 1,000-fold with minimal microbial community changes (roughly 90% of taxa had no significant differences between MEM-treated and untreated control groups). Shotgun sequencing of MEM-treated human intestinal biopsies enabled characterization of both high- and low-abundance microbial taxa, pathways and genes longitudinally along the gastrointestinal tract. We report the construction of metagenome-assembled genomes directly from human intestinal biopsies for bacteria and archaea at relative abundances as low as 1%. Analysis of metagenome-assembled genomes reveals distinct subpopulation structures between the small and large intestine for some taxa. MEM opens a path for the microbiome field to acquire deeper insights into host\u2013microbe interactions by enabling in-depth characterization of host-tissue-associated microbial communities.
", "date": "2023-10-12", "date_type": "published", "publication": "Nature Methods", "publisher": "Nature Publishing Group", "issn": "1548-7091", "official_url": "https://authors.library.caltech.edu/records/rjrx5-9bm15", "funders": { "items": [ { "grant_number": "2018-1207" }, { "grant_number": "W911NF-17-1-0402" }, { "grant_number": "RC2 DK133947" }, { "grant_number": "DGE\u20101745301" }, { "grant_number": "T32GM112592" }, {}, { "grant_number": "RC2 DK122394" }, { "grant_number": "5F30DK121470" }, { "grant_number": "DK067180" }, { "grant_number": "P30 DK42086" } ] }, "local_group": { "items": [ { "id": "Jacobs-Institute-for-Molecular-Engineering-for-Medicine" }, { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1038/s41592-023-02025-4", "primary_object": { "basename": "41592_2023_2025_Fig11_ESM.jpg", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_Fig11_ESM.jpg" }, "related_objects": [ { "basename": "41592_2023_2025_MOESM11_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_MOESM11_ESM.xlsx" }, { "basename": "41592_2023_2025_MOESM12_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_MOESM12_ESM.xlsx" }, { "basename": "41592_2023_2025_MOESM4_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_MOESM4_ESM.xlsx" }, { "basename": "41592_2023_2025_Fig10_ESM.jpg", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_Fig10_ESM.jpg" }, { "basename": "41592_2023_2025_Fig8_ESM.jpg", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_Fig8_ESM.jpg" }, { "basename": "41592_2023_2025_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_MOESM1_ESM.pdf" }, { "basename": "41592_2023_2025_MOESM10_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_MOESM10_ESM.xlsx" }, { "basename": "41592_2023_2025_MOESM5_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_MOESM5_ESM.xlsx" }, { "basename": "41592_2023_2025_MOESM9_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_MOESM9_ESM.xlsx" }, { "basename": "41592_2023_2025_MOESM14_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_MOESM14_ESM.xlsx" }, { "basename": "41592_2023_2025_MOESM15_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_MOESM15_ESM.xlsx" }, { "basename": "41592_2023_2025_MOESM6_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_MOESM6_ESM.xlsx" }, { "basename": "41592_2023_2025_MOESM7_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_MOESM7_ESM.xlsx" }, { "basename": "41592_2023_2025_MOESM8_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_MOESM8_ESM.xlsx" }, { "basename": "41592_2023_2025_Fig7_ESM.jpg", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_Fig7_ESM.jpg" }, { "basename": "41592_2023_2025_Fig9_ESM.jpg", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_Fig9_ESM.jpg" }, { "basename": "41592_2023_2025_MOESM13_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/rjrx5-9bm15/files/41592_2023_2025_MOESM13_ESM.xlsx" } ], "pub_year": "2023", "author_list": "Wu-Woods, Natalie J.; Barlow, Jacob T.; et el." }, { "id": "https://authors.library.caltech.edu/records/r9rth-vbb77", "eprint_id": 120567, "eprint_status": "archive", "datestamp": "2023-08-22 20:24:25", "lastmod": "2024-01-18 22:50:20", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Huang-Shan", "name": { "family": "Huang", "given": "Shan" }, "orcid": "0000-0002-4436-3327" }, { "id": "Wang-Kaihang", "name": { "family": "Wang", "given": "Kaihang" }, "orcid": "0000-0001-7657-8755" }, { "id": "Mayo-S-L", "name": { "family": "Mayo", "given": "Stephen L." }, "orcid": "0000-0002-9785-5018" } ] }, "title": "Genome manipulation by guide-directed Argonaute cleavage", "ispublished": "pub", "full_text_status": "public", "keywords": "Genetics", "note": "\u00a9 The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. \n\nWe thank Dr Alexei A. Aravin, Dr Andrey Kulbachinskiy, Dr Daria Esyunina and Dr David R. F. Leach for helpful discussions. We thank Rochelle A. Diamond and Jamie Tijerina for their help in flow cytometry experiments. \n\nAuthor contributions: S.H. designed and carried out experiments, with K.W. and S.L.M. providing guidance. S.H., K.W. and S.L.M. wrote the manuscript. \n\nFUNDING. Caltech Rosen Bioengineering Center Award; Shurl and Kay Curci Foundation Award. Funding for open access charge: Caltech Rosen Bioengineering Center Award. \n\nDATA AVAILABILITY. Additional notes and data are available in the Supplemental materials. \n\nConflict of interest statement. None declared.\n\nPublished - gkad188.pdf
Supplemental Material - gkad188_supplemental_file.pdf
", "abstract": "Many prokaryotic argonautes (pAgos) mediate DNA interference by using small DNA guides to cleave target DNA. A recent study shows that CbAgo, a pAgo from Clostridium butyricum, induces DNA interference between homologous sequences and generates double-stranded breaks (DSBs) in target DNAs. This mechanism enables the host to defend against invading DNAs such as plasmids and viruses. However, whether such a CbAgo-mediated DNA cleavage is mutagenic remains unexplored. Here we demonstrate that CbAgo, directed by plasmid-encoded guide sequences, can cleave genome target sites and induce chromosome recombination between downstream homologous sequences in Escherichia coli. The recombination rate correlates well with pAgo DNA cleavage activity and the mechanistic study suggests the recombination involves DSBs and RecBCD processing. In RecA-deficient E. coli strain, guide-directed CbAgo cleavage on chromosomes severely impairs cell growth, which can be utilized as counter-selection to assist Lambda-Red recombineering. These findings demonstrate the guide-directed cleavage of pAgo on the host genome is mutagenic and can lead to different outcomes according to the function of the host DNA repair machinery. We anticipate this novel DNA-guided interference to be useful in broader genetic manipulation. Our study also provides an in vivo assay to characterize or engineer pAgo DNA cleavage activity.", "date": "2023-05-08", "date_type": "published", "publication": "Nucleic Acids Research", "volume": "51", "number": "8", "publisher": "Oxford University Press", "pagerange": "4078-4085", "id_number": "CaltechAUTHORS:20230328-708572000.64", "issn": "0305-1048", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230328-708572000.64", "funders": { "items": [ { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Shurl and Kay Curci Foundation" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1093/nar/gkad188", "pmcid": "PMC10164581", "primary_object": { "basename": "gkad188.pdf", "url": "https://authors.library.caltech.edu/records/r9rth-vbb77/files/gkad188.pdf" }, "related_objects": [ { "basename": "gkad188_supplemental_file.pdf", "url": "https://authors.library.caltech.edu/records/r9rth-vbb77/files/gkad188_supplemental_file.pdf" } ], "pub_year": "2023", "author_list": "Huang, Shan; Wang, Kaihang; et el." }, { "id": "https://authors.library.caltech.edu/records/19mcr-0n267", "eprint_id": 120488, "eprint_status": "archive", "datestamp": "2023-08-22 20:27:34", "lastmod": "2023-12-22 21:34:43", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Shirzaei-Sani-Ehsan", "name": { "family": "Shirzaei Sani", "given": "Ehsan" }, "orcid": "0000-0002-4609-1505" }, { "id": "Xu-Changhao", "name": { "family": "Xu", "given": "Changhao" }, "orcid": "0000-0002-6817-3341" }, { "id": "Wang-Canran", "name": { "family": "Wang", "given": "Canran" }, "orcid": "0000-0003-3297-9041" }, { "id": "Song-Yu-Med-Eng", "name": { "family": "Song", "given": "Yu" }, "orcid": "0000-0002-4185-2256" }, { "id": "Min-Jihong", "name": { "family": "Min", "given": "Jihong" }, "orcid": "0000-0002-5788-1473" }, { "id": "Tu-Jiaobing", "name": { "family": "Tu", "given": "Jiaobing" }, "orcid": "0000-0002-7653-6640" }, { "id": "Solomon-Samuel-A", "name": { "family": "Solomon", "given": "Samuel A." }, "orcid": "0000-0001-7199-6659" }, { "id": "Li-Jiahong", "name": { "family": "Li", "given": "Jiahong" }, "orcid": "0000-0001-7938-9589" }, { "id": "Banks-Jaminelli-L", "name": { "family": "Banks", "given": "Jaminelli L." } }, { "id": "Armstrong-David-G", "name": { "family": "Armstrong", "given": "David G." } }, { "id": "Gao-Wei", "name": { "family": "Gao", "given": "Wei" }, "orcid": "0000-0002-8503-4562" } ] }, "title": "A stretchable wireless wearable bioelectronic system for multiplexed monitoring and combination treatment of infected chronic wounds", "ispublished": "pub", "full_text_status": "public", "keywords": "Multidisciplinary", "note": "\u00a9 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).\nhttps://creativecommons.org/licenses/by/4.0/.\n\nWe gratefully acknowledge critical support and infrastructure provided for this work by the Kavli Nanoscience Institute and the Biological Imaging Facility at the Beckman Institute at Caltech. \n\nThis work was supported by National Institutes of Health grant R01HL155815 (W.G.), National Institutes of Health grant R21DK13266 (W.G.), National Science Foundation grant 2145802 (W.G.), Office of Naval Research grant N00014-21-1-2483 (W.G.), Office of Naval Research grant N00014-21-1-2845 (W.G.), Heritage Medical Research Institute at the California Institute of Technology (Caltech) (W.G.), Donna and Benjamin M. Rosen Bioengineering Center at Caltech (W.G.), Rothenberg Innovation Initiative at Caltech (W.G.), Sloan Research Fellowship. \n\nAuthor contributions: Conceptualization: W.G. and E.S.S. Supervision: W.G. Methodology: W.G., E.S.S., and C.X. Investigation: E.S.S., C.X., C.W., Y.S., J.M., J.T., S.A.S., J.L., J.L.B., and D.G.A. Funding acquisition: W.G. Writing\u2014original draft: W.G., E.S.S., and C.X. Writing\u2014review and editing: C.W., Y.S., J.M., J.T., S.A.S., J.L., J.L.B., and D.G.A. \n\nCompeting interests: E.S.S. and W.G. are inventors of a patent application through California Institute of Technology describing the system and technology under the U.S. provisional patent application no. 17/993,743 (filed on 23 November 2022). The authors declare that they have no other competing interests.\n\nPublished - sciadv.adf7388.pdf
Supplemental Material - sciadv.adf7388_movie_s1.zip
Supplemental Material - sciadv.adf7388_sm.pdf
", "abstract": "Chronic nonhealing wounds are one of the major and rapidly growing clinical complications all over the world. Current therapies frequently require emergent surgical interventions, while abuse and misapplication of therapeutic drugs often lead to an increased morbidity and mortality rate. Here, we introduce a wearable bioelectronic system that wirelessly and continuously monitors the physiological conditions of the wound bed via a custom-developed multiplexed multimodal electrochemical biosensor array and performs noninvasive combination therapy through controlled anti-inflammatory antimicrobial treatment and electrically stimulated tissue regeneration. The wearable patch is fully biocompatible, mechanically flexible, stretchable, and can conformally adhere to the skin wound throughout the entire healing process. Real-time metabolic and inflammatory monitoring in a series of preclinical in vivo experiments showed high accuracy and electrochemical stability of the wearable patch for multiplexed spatial and temporal wound biomarker analysis. The combination therapy enabled substantially accelerated cutaneous chronic wound healing in a rodent model.", "date": "2023-03-24", "date_type": "published", "publication": "Science Advances", "volume": "9", "number": "12", "publisher": "American Association for the Advancement of Science", "pagerange": "eadf7388", "id_number": "CaltechAUTHORS:20230328-625234000.1", "issn": "2375-2548", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230328-625234000.1", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01HL155815" }, { "agency": "NIH", "grant_number": "R21DK13266" }, { "agency": "NSF", "grant_number": "ECCS-2145802" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-21-1-2483" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-21-1-2845" }, { "agency": "Heritage Medical Research Institute" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Rothenberg Innovation Initiative (RI2)" }, { "agency": "Alfred P. Sloan Foundation" } ] }, "local_group": { "items": [ { "id": "Kavli-Nanoscience-Institute" }, { "id": "Heritage-Medical-Research-Institute" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1126/sciadv.adf7388", "pmcid": "PMC10038347", "primary_object": { "basename": "sciadv.adf7388.pdf", "url": "https://authors.library.caltech.edu/records/19mcr-0n267/files/sciadv.adf7388.pdf" }, "related_objects": [ { "basename": "sciadv.adf7388_movie_s1.zip", "url": "https://authors.library.caltech.edu/records/19mcr-0n267/files/sciadv.adf7388_movie_s1.zip" }, { "basename": "sciadv.adf7388_sm.pdf", "url": "https://authors.library.caltech.edu/records/19mcr-0n267/files/sciadv.adf7388_sm.pdf" } ], "pub_year": "2023", "author_list": "Shirzaei Sani, Ehsan; Xu, Changhao; et el." }, { "id": "https://authors.library.caltech.edu/records/ndk7v-fhz93", "eprint_id": 118212, "eprint_status": "archive", "datestamp": "2023-08-22 18:09:55", "lastmod": "2023-12-22 23:31:03", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Abdel-Haq-Reem", "name": { "family": "Abdel-Haq", "given": "Reem" }, "orcid": "0000-0002-7418-5736" }, { "id": "Schlachetzki-Johannes-C-M", "name": { "family": "Schlachetzki", "given": "Johannes C. M." }, "orcid": "0000-0002-7801-9743" }, { "id": "Boktor-Joseph-C", "name": { "family": "Boktor", "given": "Joseph C." }, "orcid": "0000-0003-2456-1913" }, { "id": "Cantu-Jungles-Thaisa-M", "name": { "family": "Cantu-Jungles", "given": "Thaisa M." }, "orcid": "0000-0001-8928-9717" }, { "id": "Thron-Taren-M", "name": { "family": "Thron", "given": "Taren" }, "orcid": "0000-0001-9577-2617" }, { "id": "Zhang-Mengying", "name": { "family": "Zhang", "given": "Mengying" } }, { "id": "Bostick-John-W", "name": { "family": "Bostick", "given": "John W." }, "orcid": "0000-0001-8925-2447" }, { "id": "Khazaei-Tahmineh", "name": { "family": "Khazaei", "given": "Tahmineh" }, "orcid": "0000-0002-4743-2383" }, { "id": "Chilakala-Sujatha", "name": { "family": "Chilakala", "given": "Sujatha" }, "orcid": "0000-0003-1581-3381" }, { "id": "Morais-Livia-H", "name": { "family": "Morais", "given": "Livia H." }, "orcid": "0000-0002-5738-2658" }, { "id": "Humphrey-Gregory", "name": { "family": "Humphrey", "given": "Greg" } }, { "id": "Keshavarzian-Ali", "name": { "family": "Keshavarzian", "given": "Ali" }, "orcid": "0000-0002-7969-3369" }, { "id": "Katz-Jonathan-E", "name": { "family": "Katz", "given": "Jonathan E." } }, { "id": "Thomson-M-W", "name": { "family": "Thomson", "given": "Matthew" }, "orcid": "0000-0003-1021-1234" }, { "id": "Knight-Rob", "name": { "family": "Knight", "given": "Rob" }, "orcid": "0000-0002-0975-9019" }, { "id": "Gradinaru-V", "name": { "family": "Gradinaru", "given": "Viviana" }, "orcid": "0000-0001-5868-348X" }, { "id": "Hamaker-Bruce-R", "name": { "family": "Hamaker", "given": "Bruce R." }, "orcid": "0000-0001-6591-942X" }, { "id": "Glass-Christopher-K", "name": { "family": "Glass", "given": "Christopher K." }, "orcid": "0000-0003-4344-3592" }, { "id": "Mazmanian-S-K", "name": { "family": "Mazmanian", "given": "Sarkis K." }, "orcid": "0000-0003-2713-1513" } ] }, "title": "A prebiotic diet modulates microglial states and motor deficits in \u03b1-synuclein overexpressing mice", "ispublished": "pub", "full_text_status": "public", "keywords": "General Immunology and Microbiology; General Biochemistry, Genetics and Molecular Biology; General Medicine; General Neuroscience", "note": "We thank members of the Mazmanian laboratory and Dr. Catherine Oikonomou for critical review of this manuscript. We thank the Caltech Office of Laboratory Animal Research (OLAR) for animal husbandry, Dr. Wei-Li Wu for assistance with SCFA brain measurements, Dr. Sisi Chen and the Caltech Single-Cell Profiling and Engineering Center (SPEC) for technical assistance and support, the Caltech Flow Cytometry and Cell Sorting Facility for technical assistance, the Caltech Bioinformatics Center for data analysis support, and the Caltech Biological Imaging Facility (BIF) for training and use of confocal microscopes. We thank Prof. Chen-Chih Hsu's laboratory in the Department of Chemistry at National Taiwan University and BIOTOOLS Co, Ltd. for the feces and brain SCFA measurements. RA was supported by the U.S. Department of Defense, the Donna and Benjamin M Rosen Bioengineering Center, and the Biotechnology Leadership Program at Caltech. This study was funded by grants to SKM from the U.S. Department of Defense (PD160030), Heritage Medical Research Institute (HMRI-15-09-01), and by the joint efforts of the Michael J Fox Foundation for Parkinson's Research (MJFF) and the Aligning Science Across Parkinson's (ASAP) initiative. MJFF administers the grant (ASAP-000375) on behalf of ASAP and itself. \n\nThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. \n\nData availability. All datasets generated or analyzed in this study can be found through the Zenodo depository: https://doi.org/10.5281/zenodo.6377704. All experimental protocols can be found on protocols.io.", "abstract": "Parkinson's disease (PD) is a movement disorder characterized by neuroinflammation, \u03b1-synuclein pathology, and neurodegeneration. Most cases of PD are non-hereditary, suggesting a strong role for environmental factors, and it has been speculated that disease may originate in peripheral tissues such as the gastrointestinal (GI) tract before affecting the brain. The gut microbiome is altered in PD and may impact motor and GI symptoms as indicated by animal studies, although mechanisms of gut-brain interactions remain incompletely defined. Intestinal bacteria ferment dietary fibers into short-chain fatty acids, with fecal levels of these molecules differing between PD and healthy controls and in mouse models. Among other effects, dietary microbial metabolites can modulate activation of microglia, brain-resident immune cells implicated in PD. We therefore investigated whether a fiber-rich diet influences microglial function in \u03b1-synuclein overexpressing (ASO) mice, a preclinical model with PD-like symptoms and pathology. Feeding a prebiotic high-fiber diet attenuates motor deficits and reduces \u03b1-synuclein aggregation in the substantia nigra of mice. Concomitantly, the gut microbiome of ASO mice adopts a profile correlated with health upon prebiotic treatment, which also reduces microglial activation. Single-cell RNA-seq analysis of microglia from the substantia nigra and striatum uncovers increased pro-inflammatory signaling and reduced homeostatic responses in ASO mice compared to wild-type counterparts on standard diets. However, prebiotic feeding reverses pathogenic microglial states in ASO mice and promotes expansion of protective disease-associated macrophage (DAM) subsets of microglia. Notably, depletion of microglia using a CSF1R inhibitor eliminates the beneficial effects of prebiotics by restoring motor deficits to ASO mice despite feeding a prebiotic diet. These studies uncover a novel microglia-dependent interaction between diet and motor symptoms in mice, findings that may have implications for neuroinflammation and PD.", "date": "2022-11-08", "date_type": "published", "publication": "eLife", "volume": "11", "publisher": "eLife Sciences Publications", "pagerange": "Art. No. e81453", "id_number": "CaltechAUTHORS:20221202-906989500.8", "issn": "2050-084X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20221202-906989500.8", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Defense", "grant_number": "PD160030" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Caltech Biotechnology Leadership Program" }, { "agency": "Heritage Medical Research Institute", "grant_number": "HMRI-15-09-01" }, { "agency": "Michael J Fox Foundation for Parkinson's Research" }, { "agency": "Aligning Science Across Parkinson's", "grant_number": "ASAP-000375" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" }, { "id": "Heritage-Medical-Research-Institute" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.7554/elife.81453", "pmcid": "PMC9668333", "pub_year": "2022", "author_list": "Abdel-Haq, Reem; Schlachetzki, Johannes C. M.; et el." }, { "id": "https://authors.library.caltech.edu/records/2d6yn-y2n18", "eprint_id": 112886, "eprint_status": "archive", "datestamp": "2023-08-22 15:12:36", "lastmod": "2024-01-18 21:17:49", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Wang-Canran", "name": { "family": "Wang", "given": "Canran" }, "orcid": "0000-0003-3297-9041" }, { "id": "Shirzaei-Sani-Ehsan", "name": { "family": "Shirzaei Sani", "given": "Ehsan" }, "orcid": "0000-0002-4609-1505" }, { "id": "Gao-Wei", "name": { "family": "Gao", "given": "Wei" }, "orcid": "0000-0002-8503-4562" } ] }, "title": "Wearable Bioelectronics for Chronic Wound Management", "ispublished": "pub", "full_text_status": "public", "keywords": "bioelectronics; biosensors; drug delivery; wearable devices; wound healing; Electrochemistry; Condensed Matter Physics; Biomaterials; Electronic, Optical and Magnetic Materials", "note": "\u00a9 2021 Wiley-VCH GmbH. \n\nIssue Online: 25 April 2022; Version of Record online: 26 December 2021; Manuscript revised: 02 December 2021; Manuscript received: 01 November 2021. \n\nThis project was supported by the National Institutes of Health grant R01HL155815, Office of Naval Research grants N00014-21-1-2483 and N00014-21-1-2845, the Translational Research Institute for Space Health through NASA NNX16AO69A, and Rothenberg Innovation Initiative (RI2) and Rosen Center for Bioengineering at California Institute of Technology. \n\nThe authors declare no conflict of interest.\n\nAccepted Version - nihms-1795228.pdf
Cover Image - Adv_Funct_Materials_-_2022_-_Wang_-_Wearable_Bioelectronics_for_Chronic_Wound_Management__Adv__Funct__Mater__17_2022.pdf
", "abstract": "Chronic wounds are a major healthcare issue and can adversely affect the lives of millions of patients around the world. The current wound management strategies have limited clinical efficacy due to labor-intensive lab analysis requirements, need for clinicians' experiences, long-term and frequent interventions, limiting therapeutic efficiency and applicability. The growing field of flexible bioelectronics enables a great potential for personalized wound care owing to its advantages such as wearability, low-cost, and rapid and simple application. Herein, recent advances in the development of wearable bioelectronics for monitoring and management of chronic wounds are comprehensively reviewed. First, the design principles and the key features of bioelectronics that can adapt to the unique wound milieu features are introduced. Next, the current state of wound biosensors and on-demand therapeutic systems are summarized and highlighted. Furthermore, the design criteria of the integrated closed loop devices are discussed. Finally, the future perspectives and challenges in wearable bioelectronics for wound care are discussed.", "date": "2022-04-25", "date_type": "published", "publication": "Advanced Functional Materials", "volume": "32", "number": "17", "publisher": "Wiley", "pagerange": "2111022", "id_number": "CaltechAUTHORS:20220113-922790233", "issn": "1616-301X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220113-922790233", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01HL155815" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-21-1-2483" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N00014-21-1-2845" }, { "agency": "NASA", "grant_number": "NNX16AO69A" }, { "agency": "Rothenberg Innovation Initiative (RI2)" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1002/adfm.202111022", "pmcid": "PMC9518812", "primary_object": { "basename": "nihms-1795228.pdf", "url": "https://authors.library.caltech.edu/records/2d6yn-y2n18/files/nihms-1795228.pdf" }, "related_objects": [ { "basename": "Adv_Funct_Materials_-_2022_-_Wang_-_Wearable_Bioelectronics_for_Chronic_Wound_Management__Adv__Funct__Mater__17_2022.pdf", "url": "https://authors.library.caltech.edu/records/2d6yn-y2n18/files/Adv_Funct_Materials_-_2022_-_Wang_-_Wearable_Bioelectronics_for_Chronic_Wound_Management__Adv__Funct__Mater__17_2022.pdf" } ], "pub_year": "2022", "author_list": "Wang, Canran; Shirzaei Sani, Ehsan; et el." }, { "id": "https://authors.library.caltech.edu/records/9zdr7-69170", "eprint_id": 108281, "eprint_status": "archive", "datestamp": "2023-08-22 14:44:24", "lastmod": "2023-12-22 23:43:48", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Greenwald-Noah-F", "name": { "family": "Greenwald", "given": "Noah F." }, "orcid": "0000-0002-7836-4379" }, { "id": "Miller-Geneva", "name": { "family": "Miller", "given": "Geneva" } }, { "id": "Moen-Erick", "name": { "family": "Moen", "given": "Erick" }, "orcid": "0000-0002-5947-7044" }, { "name": { "family": "Kong", "given": "Alex" } }, { "name": { "family": "Kagel", "given": "Adam" } }, { "id": "Dougherty-Thomas", "name": { "family": "Dougherty", "given": "Thomas" } }, { "name": { "family": "Fullaway", "given": "Christine Camacho" } }, { "name": { "family": "McIntosh", "given": "Brianna J." }, "orcid": "0000-0003-3626-625X" }, { "name": { "family": "Leow", "given": "Ke Xuan" } }, { "id": "Schwartz-Morgan-S", "name": { "family": "Schwartz", "given": "Morgan Sarah" }, "orcid": "0000-0001-8131-9125" }, { "id": "Pavelchek-Cole", "name": { "family": "Pavelchek", "given": "Cole" }, "orcid": "0000-0001-9249-6637" }, { "id": "Cui-Sunny", "name": { "family": "Cui", "given": "Sunny" } }, { "id": "Camplisson-Isabella", "name": { "family": "Camplisson", "given": "Isabella" } }, { "name": { "family": "Bar-Tal", "given": "Omer" }, "orcid": "0000-0003-1622-3674" }, { "name": { "family": "Singh", "given": "Jaiveer" } }, { "name": { "family": "Fong", "given": "Mara" } }, { "name": { "family": "Chaudhry", "given": "Gautam" }, "orcid": "0000-0003-2240-9846" }, { "name": { "family": "Abraham", "given": "Zion" } }, { "name": { "family": "Moseley", "given": "Jackson" } }, { "name": { "family": "Warshawsky", "given": "Shiri" } }, { "name": { "family": "Soon", "given": "Erin" } }, { "name": { "family": "Greenbaum", "given": "Shirley" }, "orcid": "0000-0002-0680-7652" }, { "name": { "family": "Risom", "given": "Tyler" }, "orcid": "0000-0003-1089-9542" }, { "name": { "family": "Hollmann", "given": "Travis" }, "orcid": "0000-0003-1599-0433" }, { "name": { "family": "Bendall", "given": "Sean C." }, "orcid": "0000-0003-1341-2453" }, { "name": { "family": "Keren", "given": "Leeat" }, "orcid": "0000-0002-6799-6303" }, { "id": "Graf-William", "name": { "family": "Graf", "given": "Will" }, "orcid": "0000-0003-0460-4605" }, { "name": { "family": "Angelo", "given": "Michael" }, "orcid": "0000-0003-1531-5067" }, { "id": "Van-Valen-D", "name": { "family": "Van Valen", "given": "David" }, "orcid": "0000-0001-7534-7621" } ] }, "title": "Whole-cell segmentation of tissue images with human-level performance using large-scale data annotation and deep learning", "ispublished": "pub", "full_text_status": "public", "keywords": "Image processing; Imaging; Software", "note": "\u00a9 2021 Nature Publishing Group. \n\nReceived 01 March 2021; Accepted 14 September 2021; Published 18 November 2021. \n\nWe thank K. Borner, L. Cai, M. Covert, A. Karpathy, S. Quake and M. Thomson for interesting discussions; D. Glass and E. McCaffrey for feedback on the manuscript; T. Vora for copy editing; R. Angoshtari, G. Barlow, B. Bodenmiller, C. Carey, R. Coffey, A. Delmastro, C. Egelston, M. Hoppe, H. Jackson, A. Jeyasekharan, S. Jiang, Y. Kim, E. McCaffrey, E. McKinley, M. Nelson, S.-B. Ng, G. Nolan, S. Patel, Y. Peng, D. Philips, R. Rashid, S. Rodig, S. Santagata, C. Schuerch, D. Schulz, Di. Simons, P. Sorger, J. Weirather and Y. Yuan for providing imaging data for TissueNet; the crowd annotators who powered our human-in-the-loop pipeline; and all patients who donated samples for this study. This work was supported by grants from the Shurl and Kay Curci Foundation, the Rita Allen Foundation, the Susan E. Riley Foundation, the Pew Heritage Trust, the Alexander and Margaret Stewart Trust, the Heritage Medical Research Institute, the Paul Allen Family Foundation through the Allen Discovery Centers at Stanford and Caltech, the Rosen Center for Bioengineering at Caltech and the Center for Environmental and Microbial Interactions at Caltech (D.V.V.). This work was also supported by 5U54CA20997105, 5DP5OD01982205, 1R01CA24063801A1, 5R01AG06827902, 5UH3CA24663303, 5R01CA22952904, 1U24CA22430901, 5R01AG05791504 and 5R01AG05628705 from NIH, W81XWH2110143 from DOD, and other funding from the Bill and Melinda Gates Foundation, Cancer Research Institute, the Parker Center for Cancer Immunotherapy and the Breast Cancer Research Foundation (M.A.). N.F.G. was supported by NCI CA246880-01 and the Stanford Graduate Fellowship. B.J.M. was supported by the Stanford Graduate Fellowship and Stanford Interdisciplinary Graduate Fellowship. T.D. was supported by the Schmidt Academy for Software Engineering at Caltech. \n\nData availability: The TissueNet dataset is available at https://datasets.deepcell.org/ for noncommercial use. \n\nCode availability: All software for dataset construction, model training, deployment and analysis is available on our github page https://github.com/vanvalenlab/intro-to-deepcell. All code to generate the figures in this paper is available at https://github.com/vanvalenlab/publication-figures/tree/master/2021-Greenwald_Miller_et_al-Mesmer. \n\nThese authors contributed equally: Noah F. Greenwald, Geneva Miller. \n\nAuthor Contributions: N.F.G., L.K., M.A. and D.V.V. conceived the project. E.M. and D.V.V. conceived the human-in-the-loop approach. L.K. and M.A. conceived the whole-cell segmentation approach. G.M., T.D., E.M., W.G. and D.V.V. developed DeepCell Label. G.M., N.F.G., E.M., I.C., W.G. and D.V.V. developed the human-in-the-loop pipeline. M.S.S., C.P., W.G. and D.V.V. developed Mesmer's deep learning architecture. W.G., N.F.G. and D.V.V. developed model training software. C.P. and W.G. developed cloud deployment. M.S.S., S.C., W.G. and D.V.V. developed metrics software. W.G. developed plugins. N.F.G., A.\u2009Kong, A.\u2009Kagel, J.S. and O.B.-T. developed the multiplex image analysis pipeline. A.\u2009Kagel and G.M. developed the pathologist evaluation software. N.F.G., G.M. and T.H. supervised training data creation. N.F.G., C.C.F., B.J.M., K.X.L., M.F., G.C., Z.A., J.M. and S.W. performed quality control on the training data. E.S., S.G. and T.R. generated MIBI-TOF data for morphological analyses. S.C.B. helped with experimental design. N.F.G., W.G. and D.V.V. trained the models. N.F.G., W.G., G.M. and D.V.V. performed data analysis. N.F.G., G.M., M.A. and D.V.V. wrote the manuscript. M.A. and D.V.V. supervised the project. All authors provided feedback on the manuscript. \n\nPeer review information: Nature Biotechnology thanks the anonymous reviewers for their contribution to the peer review of this work.\n\nSubmitted - 2021.03.01.431313v1.full.pdf
Supplemental Material - 41587_2021_1094_Fig10_ESM.webp
Supplemental Material - 41587_2021_1094_Fig7_ESM.webp
Supplemental Material - 41587_2021_1094_Fig8_ESM.webp
Supplemental Material - 41587_2021_1094_Fig9_ESM.webp
Supplemental Material - 41587_2021_1094_MOESM1_ESM.pdf
", "abstract": "A principal challenge in the analysis of tissue imaging data is cell segmentation\u2014the task of identifying the precise boundary of every cell in an image. To address this problem we constructed TissueNet, a dataset for training segmentation models that contains more than 1\u2009million manually labeled cells, an order of magnitude more than all previously published segmentation training datasets. We used TissueNet to train Mesmer, a deep-learning-enabled segmentation algorithm. We demonstrated that Mesmer is more accurate than previous methods, generalizes to the full diversity of tissue types and imaging platforms in TissueNet, and achieves human-level performance. Mesmer enabled the automated extraction of key cellular features, such as subcellular localization of protein signal, which was challenging with previous approaches. We then adapted Mesmer to harness cell lineage information in highly multiplexed datasets and used this enhanced version to quantify cell morphology changes during human gestation. All code, data and models are released as a community resource.", "date": "2022-04", "date_type": "published", "publication": "Nature Biotechnology", "volume": "40", "number": "4", "publisher": "Nature Publishing Group", "pagerange": "555-565", "id_number": "CaltechAUTHORS:20210303-070232817", "issn": "1087-0156", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210303-070232817", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Shurl and Kay Curci Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Susan E. Riley Foundation" }, { "agency": "Pew Heritage Trust" }, { "agency": "Alexander and Margaret Stewart Trust" }, { "agency": "Heritage Medical Research Institute" }, { "agency": "Paul Allen Family Foundation" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" }, { "agency": "NIH", "grant_number": "5U54CA20997105" }, { "agency": "NIH", "grant_number": "5DP5OD01982205" }, { "agency": "NIH", "grant_number": "1R01CA24063801A1" }, { "agency": "NIH", "grant_number": "5R01AG06827902" }, { "agency": "NIH", "grant_number": "5UH3CA24663303" }, { "agency": "NIH", "grant_number": "5R01CA22952904" }, { "agency": "NIH", "grant_number": "1U24CA22430901" }, { "agency": "NIH", "grant_number": "5R01AG05791504" }, { "agency": "NIH", "grant_number": "5R01AG05628705" }, { "agency": "Department of Defense", "grant_number": "W81XWH2110143" }, { "agency": "Bill and Melinda Gates Foundation" }, { "agency": "Cancer Research Institute" }, { "agency": "Parker Institute for Cancer Immunotherapy" }, { "agency": "Breast Cancer Research Foundation" }, { "agency": "National Cancer Institute", "grant_number": "CA246880-01" }, { "agency": "Stanford University" }, { "agency": "Schmidt Futures Program" } ] }, "local_group": { "items": [ { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1038/s41587-021-01094-0", "pmcid": "PMC9010346", "primary_object": { "basename": "2021.03.01.431313v1.full.pdf", "url": "https://authors.library.caltech.edu/records/9zdr7-69170/files/2021.03.01.431313v1.full.pdf" }, "related_objects": [ { "basename": "41587_2021_1094_Fig10_ESM.webp", "url": "https://authors.library.caltech.edu/records/9zdr7-69170/files/41587_2021_1094_Fig10_ESM.webp" }, { "basename": "41587_2021_1094_Fig7_ESM.webp", "url": "https://authors.library.caltech.edu/records/9zdr7-69170/files/41587_2021_1094_Fig7_ESM.webp" }, { "basename": "41587_2021_1094_Fig8_ESM.webp", "url": "https://authors.library.caltech.edu/records/9zdr7-69170/files/41587_2021_1094_Fig8_ESM.webp" }, { "basename": "41587_2021_1094_Fig9_ESM.webp", "url": "https://authors.library.caltech.edu/records/9zdr7-69170/files/41587_2021_1094_Fig9_ESM.webp" }, { "basename": "41587_2021_1094_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/9zdr7-69170/files/41587_2021_1094_MOESM1_ESM.pdf" } ], "pub_year": "2022", "author_list": "Greenwald, Noah F.; Miller, Geneva; et el." }, { "id": "https://authors.library.caltech.edu/records/k7p4y-d6485", "eprint_id": 113452, "eprint_status": "archive", "datestamp": "2023-08-22 13:59:52", "lastmod": "2023-12-22 23:34:04", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Shen-Cheng", "name": { "family": "Shen", "given": "Cheng" }, "orcid": "0000-0001-7136-4715" }, { "id": "Lamba-Adiyant", "name": { "family": "Lamba", "given": "Adiyant" } }, { "id": "Zhu-Meng", "name": { "family": "Zhu", "given": "Meng" }, "orcid": "0000-0001-6157-8840" }, { "id": "Zhang-Ray", "name": { "family": "Zhang", "given": "Ray" } }, { "id": "Zernicka-Goetz-M", "name": { "family": "Zernicka-Goetz", "given": "Magdalena" }, "orcid": "0000-0002-7004-2471" }, { "id": "Yang-Changhuei", "name": { "family": "Yang", "given": "Changhuei" }, "orcid": "0000-0001-8791-0354" } ] }, "title": "Stain-free detection of embryo polarization using deep learning", "ispublished": "pub", "full_text_status": "public", "keywords": "Computational science; Developmental biology; Embryogenesis; Embryology; Multidisciplinary", "note": "\u00a9 The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. \n\nReceived 22 October 2021; Accepted 10 January 2022; Published 14 February 2022. \n\nWe thank all colleagues in the C.Y. and M.Z.-G. labs for helpful suggestions and feedback. We also thank all human volunteers. We thank all funding sources: Wellcome Trust (098287/Z/12/Z) (MZG), Leverhulme Trust (RPG- 2018-085) (MZG), Open Philanthropy/Silicon Valley (MZG), Weston Havens Foundations (MZG), NIH R01 HD100456-01A1 (MZG), Rosen Bioengineering Center Pilot Research Grant Award (9900050) (CY, MZG), Medical Research Council (AL), Cambridge Vice Chancellor's Award Fund (AL). \n\nData availability: The testing dataset is available on https://github.com/Scott-Sheen/AI4Embryo for model validation use and academic purposes only. All other datasets generated and analyzed in the current study (including larger training image dataset) are available from the corresponding author (M.Z.-G) on reasonable request. \n\nCode availability: The training code for the single DCNNs and the testing code for the ensemble DL model are available at: https://github.com/Scott-Sheen/AI4Embryo. \n\nAuthor Contributions: These authors contributed equally: Cheng Shen and Adiyant Lamba. \n\nC.S. and A.L. were responsible for planning project directions, interpretation of results and optimization of the model. C.S. was responsible for the design of the model. M.Z. and A.L. were responsible for embryo recordings and assembly of the dataset. A.L. was responsible for annotating embryo images. The project was conceived by M.Z., M.Z.-G and C.Y. and supervised by M.Z.-G and C.Y. The manuscript was written by A.L., C.S., C.Y. and M.Z.-G. R.Z. edited the manuscript. \n\nThe authors declare no competing interests.\n\nPublished - s41598-022-05990-6.pdf
Submitted - 2111.05315.pdf
Supplemental Material - 41598_2022_5990_MOESM1_ESM.docx
", "abstract": "Polarization of the mammalian embryo at the right developmental time is critical for its development to term and would be valuable in assessing the potential of human embryos. However, tracking polarization requires invasive fluorescence staining, impermissible in the in vitro fertilization clinic. Here, we report the use of artificial intelligence to detect polarization from unstained time-lapse movies of mouse embryos. We assembled a dataset of bright-field movie frames from 8-cell-stage embryos, side-by-side with corresponding images of fluorescent markers of cell polarization. We then used an ensemble learning model to detect whether any bright-field frame showed an embryo before or after onset of polarization. Our resulting model has an accuracy of 85% for detecting polarization, significantly outperforming human volunteers trained on the same data (61% accuracy). We discovered that our self-learning model focuses upon the angle between cells as one known cue for compaction, which precedes polarization, but it outperforms the use of this cue alone. By compressing three-dimensional time-lapsed image data into two-dimensions, we are able to reduce data to an easily manageable size for deep learning processing. In conclusion, we describe a method for detecting a key developmental feature of embryo development that avoids clinically impermissible fluorescence staining.", "date": "2022-02-14", "date_type": "published", "publication": "Scientific Reports", "volume": "12", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 2404", "id_number": "CaltechAUTHORS:20220215-496417800", "issn": "2045-2322", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220215-496417800", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Wellcome Trust", "grant_number": "098287/Z/12/Z" }, { "agency": "Leverhulme Trust", "grant_number": "RPG-2018-085" }, { "agency": "Open Philanthropy" }, { "agency": "Weston Havens Foundation" }, { "agency": "NIH", "grant_number": "R01 HD100456-01A1" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center", "grant_number": "9900050" }, { "agency": "Medical Research Council (UK)" }, { "agency": "University of Cambridge" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1038/s41598-022-05990-6", "primary_object": { "basename": "2111.05315.pdf", "url": "https://authors.library.caltech.edu/records/k7p4y-d6485/files/2111.05315.pdf" }, "related_objects": [ { "basename": "41598_2022_5990_MOESM1_ESM.docx", "url": "https://authors.library.caltech.edu/records/k7p4y-d6485/files/41598_2022_5990_MOESM1_ESM.docx" }, { "basename": "s41598-022-05990-6.pdf", "url": "https://authors.library.caltech.edu/records/k7p4y-d6485/files/s41598-022-05990-6.pdf" } ], "pub_year": "2022", "author_list": "Shen, Cheng; Lamba, Adiyant; et el." }, { "id": "https://authors.library.caltech.edu/records/r8qh8-y4065", "eprint_id": 108641, "eprint_status": "archive", "datestamp": "2023-08-20 06:53:20", "lastmod": "2023-12-22 23:44:25", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Savela-Emily-S", "name": { "family": "Savela", "given": "Emily S." }, "orcid": "0000-0001-9614-4276" }, { "id": "Winnett-Alexander-Viloria", "name": { "family": "Winnett", "given": "Alexander Viloria" }, "orcid": "0000-0002-7338-5605" }, { "id": "Romano-Anna-E", "name": { "family": "Romano", "given": "Anna E." }, "orcid": "0000-0003-1871-1727" }, { "id": "Porter-Michael-K", "name": { "family": "Porter", "given": "Michael K." }, "orcid": "0000-0002-0777-7563" }, { "id": "Shelby-Natasha", "name": { "family": "Shelby", "given": "Natasha" }, "orcid": "0000-0001-9097-3663" }, { "id": "Akana-Reid", "name": { "family": "Akana", "given": "Reid" }, "orcid": "0000-0003-4422-587X" }, { "id": "Ji-Jenny", "name": { "family": "Ji", "given": "Jenny" }, "orcid": "0000-0002-7901-5605" }, { "id": "Cooper-Matthew-M", "name": { "family": "Cooper", "given": "Matthew M." }, "orcid": "0000-0002-5868-5159" }, { "id": "Schlenker-Noah-W", "name": { "family": "Schlenker", "given": "Noah W." }, "orcid": "0000-0002-8581-4403" }, { "id": "Reyes-Jessica-A", "name": { "family": "Reyes", "given": "Jessica A." }, "orcid": "0000-0002-5507-7633" }, { "id": "Carter-Alyssa-M", "name": { "family": "Carter", "given": "Alyssa M." }, "orcid": "0000-0002-2776-9421" }, { "id": "Barlow-Jacob-T", "name": { "family": "Barlow", "given": "Jacob T." }, "orcid": "0000-0002-1842-4835" }, { "id": "Tognazzini-Colten", "name": { "family": "Tognazzini", "given": "Colten" } }, { "id": "Feaster-Matthew", "name": { "family": "Feaster", "given": "Matthew" }, "orcid": "0000-0001-9966-2845" }, { "id": "Goh-Ying-Ying", "name": { "family": "Goh", "given": "Ying-Ying" }, "orcid": "0000-0001-5136-7214" }, { "id": "Ismagilov-R-F", "name": { "family": "Ismagilov", "given": "Rustem F." }, "orcid": "0000-0002-3680-4399" } ] }, "title": "Quantitative SARS-CoV-2 Viral-Load Curves in Paired Saliva Samples and Nasal Swabs Inform Appropriate Respiratory Sampling Site and Analytical Test Sensitivity Required for Earliest Viral Detection", "ispublished": "pub", "full_text_status": "public", "keywords": "RT-qPCR, COVID-19, case-ascertained, diagnostics, household study,\nlongitudinal sampling, nasal swab, presymptomatic, saliva, surveillance, transmission", "note": "\u00a9 2022 Savela et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. \n\nReceived 24 August 2021; Returned for modification 21 September 2021; Accepted 10 December 2021; Accepted manuscript posted online 15 December 2021; Published 16 February 2022. \n\nWe thank Lauriane Quenee, Junie Hildebrandt, Grace Fisher-Adams, RuthAnne Bevier, Chantal D'Apuzzo, Ralph Adolphs, Victor Rivera, Steve Chapman, Gary Waters, Leonard Edwards, Gaylene Ursua, Cynthia Ramos, and Shannon Yamashita for their assistance and advice on study implementation and/or administration. We thank Jessica Leong, Jessica Slagle, Mika Walton, Angel Navarro, Daniel Brenner, and Ojas Pradhan for volunteering their time to help with this study, Si Hyung Jin for helping with a literature review, and Mary Arrastia for providing biosafety support. We thank Maira Phelps, Lienna Chan, Lucy Li, Dan Lu, and Amy Kistler at the Chan Zuckerberg Biohub for performing SARS-CoV-2 sequencing. We thank Angie Cheng, Susan Magdaleno, Christian Kis, Monica Herrera, and Zaina Lemeir for technical discussions regarding saliva extraction and ddPCR detection. We thank Jennifer Fulcher, Debika Bhattacharya, and Matthew Bidwell Goetz for their ideas on potential study populations and early study design. We thank Omai Garner and David Beenhouwer for providing materials for initial nasal-swab validation. We thank Martin Hill, Alma Sanchez, Scott Kim, Debbie Noble, Nina Paddock, Whitney Harrison, Emily Holman, Isaac Turner, Vivek Desai, Luke Wade, Tom Mayell, Stu Miller, and Jennifer Howes for their support with recruitment. We thank Allison Rhines, Karen Heichman, and Dan Wattendorf for valuable discussions. Finally, we thank all the case investigators and contact tracers at the Pasadena Public Health Department and the City of Long Beach Department of Health & Human Services for their efforts in study recruitment and their work in the pandemic response. \n\nR.F.I. is a cofounder, consultant, and a director and has stock ownership of Talis Biomedical Corp. In addition, R.F.I. is an inventor on a series of patents licensed by the University of Chicago to Bio-Rad Laboratories, Inc., in the context of ddPCR. \n\nThis study is based on research funded in part by the Bill & Melinda Gates Foundation (INV-023124). The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation. This work was also funded by the Ronald and Maxine Linde Center for New Initiatives at the California Institute of Technology and the Jacobs Institute for Molecular Engineering for Medicine at the California Institute of Technology. A.V.W. is supported by a National Institutes of Health NIGMS predoctoral training grant (GM008042) and a UCLA DGSOM Geffen fellowship; M.M.C. is supported by a Caltech graduate student fellowship, and M.K.P. and J.T.B. are each partially supported by a National Institutes of Health Biotechnology Leadership Predoctoral Training Program (BLP) fellowship from Caltech's Donna and Benjamin M. Rosen Bioengineering Center (T32GM112592).\n\nPublished - jcm.01785-21.pdf
Submitted - 2021.04.02.21254771v2.full.pdf
Supplemental Material - jcm.01785-21-s0001.pdf
", "abstract": "Early detection of SARS-CoV-2 infection is critical to reduce asymptomatic and presymptomatic transmission, curb the spread of variants, and maximize treatment efficacy. Low-analytical-sensitivity nasal-swab testing is commonly used for surveillance and symptomatic testing, but the ability of these tests to detect the earliest stages of infection has not been established. In this study, conducted between September 2020 and June 2021 in the greater Los Angeles County, California, area, initially SARS-CoV-2-negative household contacts of individuals diagnosed with COVID-19 prospectively self-collected paired anterior-nares nasal-swab and saliva samples twice daily for viral-load quantification by high-sensitivity reverse-transcription quantitative PCR (RT-qPCR) and digital-RT-PCR assays. We captured viral-load profiles from the incidence of infection for seven individuals and compared diagnostic sensitivities between respiratory sites. Among unvaccinated persons, testing saliva with a high-analytical-sensitivity assay detected infection up to 4.5\u2009days before viral loads in nasal swabs reached concentrations detectable by low-analytical-sensitivity nasal-swab tests. For most participants, nasal swabs reached higher peak viral loads than saliva but were undetectable or at lower loads during the first few days of infection. High-analytical-sensitivity saliva testing was most reliable for earliest detection. Our study illustrates the value of acquiring early (within hours after a negative high-sensitivity test) viral-load profiles to guide the appropriate analytical sensitivity and respiratory site for detecting earliest infections. Such data are challenging to acquire but critical to designing optimal testing strategies with emerging variants in the current pandemic and to respond to future viral pandemics.", "date": "2022-02", "date_type": "published", "publication": "Journal of Clinical Microbiology", "volume": "60", "number": "2", "publisher": "American Society for Microbiology", "pagerange": "Art. No. e01785-21", "id_number": "CaltechAUTHORS:20210407-080559241", "issn": "0095-1137", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210407-080559241", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Bill and Melinda Gates Foundation", "grant_number": "INV-023124" }, { "agency": "Ronald and Maxine Linde Center for New Initiatives" }, { "agency": "Jacobs Institute for Molecular Engineering for Medicine" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "GM008042" }, { "agency": "UCLA" }, { "agency": "Caltech" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "T32GM112592" } ] }, "local_group": { "items": [ { "id": "COVID-19" }, { "id": "Rosen-Bioengineering-Center" }, { "id": "Jacobs-Institute-for-Molecular-Engineering-for-Medicine" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1128/JCM.01785-21", "pmcid": "PMC8849374", "primary_object": { "basename": "2021.04.02.21254771v2.full.pdf", "url": "https://authors.library.caltech.edu/records/r8qh8-y4065/files/2021.04.02.21254771v2.full.pdf" }, "related_objects": [ { "basename": "jcm.01785-21-s0001.pdf", "url": "https://authors.library.caltech.edu/records/r8qh8-y4065/files/jcm.01785-21-s0001.pdf" }, { "basename": "jcm.01785-21.pdf", "url": "https://authors.library.caltech.edu/records/r8qh8-y4065/files/jcm.01785-21.pdf" } ], "pub_year": "2022", "author_list": "Savela, Emily S.; Winnett, Alexander Viloria; et el." }, { "id": "https://authors.library.caltech.edu/records/kr4aw-77227", "eprint_id": 112183, "eprint_status": "archive", "datestamp": "2023-09-22 22:31:02", "lastmod": "2023-10-23 23:23:29", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ramachandran-Karthik", "name": { "family": "Ramachandran", "given": "Karthik" }, "orcid": "0000-0003-1820-7555" }, { "id": "Shao-Zixuan", "name": { "family": "Shao", "given": "Zixuan" }, "orcid": "0000-0002-4676-6023" }, { "id": "Di-Luccio-Tiziana", "name": { "family": "Di Luccio", "given": "Tiziana" }, "orcid": "0000-0001-8947-0655" }, { "id": "Shen-Bo", "name": { "family": "Shen", "given": "Bo" } }, { "id": "Ruiz-Bello-Edgar-E", "name": { "family": "Ruiz Bello", "given": "Edgar E." } }, { "id": "Tammaro-Loredana", "name": { "family": "Tammaro", "given": "Loredana" } }, { "id": "Villani-Fulvia", "name": { "family": "Villani", "given": "Fulvia" }, "orcid": "0000-0001-7301-9819" }, { "id": "Loffredo-Fausta", "name": { "family": "Loffredo", "given": "Fausta" } }, { "id": "Borriello-Carmela", "name": { "family": "Borriello", "given": "Carmela" }, "orcid": "0000-0001-8412-530X" }, { "id": "Di-Benedetto-Francesca", "name": { "family": "Di Benedetto", "given": "Francesca" } }, { "id": "Magee-Eimear", "name": { "family": "Magee", "given": "Eimear" } }, { "id": "McNally-Tony", "name": { "family": "McNally", "given": "Tony" }, "orcid": "0000-0001-5436-4211" }, { "id": "Kornfield-J-A", "name": { "family": "Kornfield", "given": "Julia A." }, "orcid": "0000-0001-6746-8634" } ] }, "title": "Tungsten disulfide nanotubes enhance flow-induced crystallization and radio-opacity of polylactide without adversely affecting in vitro toxicity", "ispublished": "pub", "full_text_status": "public", "keywords": "Polylactide (PLA); Tungsten disulfide (WS2) nanotubes; Flow-induced crystallization; Biocompatible nanocomposites; Coronary Heart Disease; Bioresorbable Vascular Scaffolds (BVS); Molecular Biology; Biomedical Engineering; Biochemistry; Biomaterials; General Medicine; Biotechnology", "note": "\u00a9 2021 Acta Materialia Inc. Published by Elsevier. \n\nReceived 26 July 2021, Revised 17 October 2021, Accepted 4 November 2021, Available online 17 November 2021. \n\nThis research used resources of the Advanced Photon Source (APS), a US Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract DE-AC02-06CH11357. We are grateful to the staff of APS beamline 5-D-D, Steven Weigand and James Rix in particular, for their invaluable assistance in acquiring synchrotron X-ray scattering data. We are also indebted to Dan Zhou, a graduate student in the Kornfield group, Dr. Jeremy Wei, a former research scientist in the Kornfield group, and Mark Ladinsky, a scientist at the Caltech electron microscopy core, for their help in microtoming PLA/PLA-WSNT sections and acquiring GPC data and TEM images respectively. This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Sk\u0142odowska-Curie grant agreement No 691238, the Jacobs Institute for Molecular Engineering for Medicine at Caltech, the Rosen Center for Bioengineering at Caltech, a National Institutes of Health (NIH) training grant (T32GM112592) and the National Heart, Lung, and Blood Institute of the NIH under Award Number F31HL137308. \n\nThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\n\nAccepted Version - nihms-1757868.pdf
Supplemental Material - 1-s2.0-S1742706121007467-mmc1.docx
Supplemental Material - 1-s2.0-S1742706121007467-mmc2.zip
Supplemental Material - 1-s2.0-S1742706121007467-mmc3.zip
", "abstract": "Treatment of vascular disease, from peripheral ischemia to coronary heart disease (CHD), is poised for transformation with the introduction of transient implants designed to \"scaffold\" regeneration of blood vessels and ultimately leave nothing behind. Improved materials could expand the use of these devices. Here, we examine one of the leading polymers for bioresorbable scaffolds (BRS), polylactide (PLA), as the matrix of nanocomposites with tungsten disulfide (WS\u2082) nanotubes (WSNT), which may provide mechanical reinforcement and enhance radio-opacity. We evaluate in vitro cytotoxicity using vascular cells, flow-induced crystallization and radio-opacity of PLA-WSNT nanocomposites at low WSNT concentration. A small amount of WSNT (0.1 wt%) can effectively promote oriented crystallization of PLA without compromising molecular weight. And radio-opacity improves significantly: as little as 0.5 to 1 wt% WSNT doubles the radio-opacity of PLA-WSNT relative to PLA at 17 keV. The results suggest that a single component, WSNT, has the potential to increase the strength of BRS to enable thinner devices and increase radio-opacity to improve intraoperative visualization. The in vitro toxicity results indicate that PLA-WSNT nanocomposites are worthy of investigation in vivo. Although substantial further preclinical studies are needed, PLA-WSNT nanocomposites may provide a complement of material properties that may improve BVS and expand the range of lesions that can be treated using transient implants.", "date": "2022-01-15", "date_type": "published", "publication": "Acta Biomaterialia", "volume": "138", "publisher": "Elsevier", "pagerange": "313-326", "id_number": "CaltechAUTHORS:20211202-230941847", "issn": "1742-7061", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211202-230941847", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Energy (DOE)", "grant_number": "DE-AC02-06CH11357" }, { "agency": "Marie Curie Fellowship", "grant_number": "691238" }, { "agency": "Jacobs Institute for Molecular Engineering for Medicine" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "T32GM112592" }, { "agency": "NIH Postdocotral Fellowship", "grant_number": "F31HL137308" } ] }, "local_group": { "items": [ { "id": "Jacobs-Institute-for-Molecular-Engineering-for-Medicine" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1016/j.actbio.2021.11.005", "pmcid": "PMC9505057", "primary_object": { "basename": "1-s2.0-S1742706121007467-mmc2.zip", "url": "https://authors.library.caltech.edu/records/kr4aw-77227/files/1-s2.0-S1742706121007467-mmc2.zip" }, "related_objects": [ { "basename": "1-s2.0-S1742706121007467-mmc3.zip", "url": "https://authors.library.caltech.edu/records/kr4aw-77227/files/1-s2.0-S1742706121007467-mmc3.zip" }, { "basename": "nihms-1757868.pdf", "url": "https://authors.library.caltech.edu/records/kr4aw-77227/files/nihms-1757868.pdf" }, { "basename": "1-s2.0-S1742706121007467-mmc1.docx", "url": "https://authors.library.caltech.edu/records/kr4aw-77227/files/1-s2.0-S1742706121007467-mmc1.docx" } ], "pub_year": "2022", "author_list": "Ramachandran, Karthik; Shao, Zixuan; et el." }, { "id": "https://authors.library.caltech.edu/records/tmw0j-mph48", "eprint_id": 111829, "eprint_status": "archive", "datestamp": "2023-08-22 11:54:59", "lastmod": "2023-12-22 23:33:09", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Barlow-Jacob-T", "name": { "family": "Barlow", "given": "Jacob T." }, "orcid": "0000-0002-1842-4835" }, { "id": "Leite-Gabriela", "name": { "family": "Leite", "given": "Gabriela" }, "orcid": "0000-0001-5772-7735" }, { "id": "Romano-Anna-E", "name": { "family": "Romano", "given": "Anna E." }, "orcid": "0000-0003-1871-1727" }, { "id": "Sedighi-Rashin", "name": { "family": "Sedighi", "given": "Rashin" } }, { "id": "Chang-Christine", "name": { "family": "Chang", "given": "Christine" }, "orcid": "0000-0003-0179-7800" }, { "id": "Celly-Shreya", "name": { "family": "Celly", "given": "Shreya" }, "orcid": "0000-0002-5896-457X" }, { "id": "Rezaie-Ali", "name": { "family": "Rezaie", "given": "Ali" }, "orcid": "0000-0002-0106-372X" }, { "id": "Mathur-Ruchi", "name": { "family": "Mathur", "given": "Ruchi" }, "orcid": "0000-0003-1053-6557" }, { "id": "Pimentel-Mark", "name": { "family": "Pimentel", "given": "Mark" }, "orcid": "0000-0002-0619-5115" }, { "id": "Ismagilov-R-F", "name": { "family": "Ismagilov", "given": "Rustem F." }, "orcid": "0000-0002-3680-4399" } ] }, "title": "Quantitative sequencing clarifies the role of disruptor taxa, oral microbiota, and strict anaerobes in the human small-intestine microbiome", "ispublished": "pub", "full_text_status": "public", "keywords": "Duodenum; Saliva; HACEK; Human small intestinal microbiome; IBS; SIBO; Enterobacteriaceae; Lactobacillus; Constipation; Bloating", "note": "\u00a9 The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. \n\nReceived 15 June 2021; Accepted 14 September 2021; Published 02 November 2021. \n\nWe thank the Caltech Bioinformatics Resource Center for assistance with statistical analyses, Jenny Ji for related analyses and Natasha Shelby for contributions to writing and editing this manuscript. We acknowledge OpenMoji for use of the saliva and stool graphics in Fig. 1. We thank Stacy Weitsman, Walter Morales and Maria Jesus Villanueva-Milan from MAST for assistance with sample processing and data curation from the REIMAGINE study. We also thank the Gastroenterology team at Cedars-Sinai Medical Center for assistance with patient recruitment and endoscopy procedures. \n\nThis work was supported in part by the Kenneth Rainin Foundation (2018-1207), the Jacobs Institute for Molecular Engineering for Medicine, and a National Institutes of Health Biotechnology Leadership Pre-doctoral Training Program (BLP) fellowship from Caltech's Donna and Benjamin M. Rosen Bioengineering Center (T32GM112592, to J.T.B.). The funders had no role in the design of the study, the collection, analysis, and interpretation of data, nor in writing the manuscript. \n\nJacob T. Barlow and Gabriela Leite contributed equally to this work. \n\nAuthor Contributions: Conceptualization, J.T.B., G.L., R.M., M.P., and R.F.I.. Methodology, J.T.B., G.L., S.C., R.S., C.C.. Formal analysis, J.T.B.. Investigation, J.T.B, G.L., and A.E.R. Resources, G.L. Data curation, J.T.B., and G.L. Writing\u2014original draft, J.T.B. Writing\u2014review and editing, J.T.B., G.L., A.R., R.M., M.P., and R.F.I. Visualization, J.T.B. Supervision, M.P., and R.F.I. The author(s) read and approved the final manuscript. \n\nEthics approval and consent to participate: The study was reviewed and approved by the Cedars-Sinai Medical Center IRB (Protocol #00035192). All participants provided written informed consent prior to participation. \n\nConsent for publication: Not applicable. \n\nCompeting interests: The quantitative sequencing technology described in this publication is the subject of a patent application filed by Caltech. R.F.I. receives patent royalties from Bio-Rad related to droplet digital PCR.\n\nPublished - s40168-021-01162-2.pdf
Supplemental Material - 40168_2021_1162_MOESM2_ESM.docx
Supplemental Material - 40168_2021_1162_MOESM3_ESM.xlsx
", "abstract": "Background: Upper gastrointestinal (GI) disorders and abdominal pain afflict between 12 and 30% of the worldwide population and research suggests these conditions are linked to the gut microbiome. Although large-intestine microbiota have been linked to several GI diseases, the microbiota of the human small intestine and its relation to human disease has been understudied. The small intestine is the major site for immune surveillance in the gut, and compared with the large intestine, it has greater than 100 times the surface area and a thinner and more permeable mucus layer. \n\nResults: Using quantitative sequencing, we evaluated total and taxon-specific absolute microbial loads from 250 duodenal-aspirate samples and 21 paired duodenum-saliva samples from participants in the REIMAGINE study. Log-transformed total microbial loads spanned 5 logs and were normally distributed. Paired saliva-duodenum samples suggested potential transmission of oral microbes to the duodenum, including organisms from the HACEK group. Several taxa, including Klebsiella, Escherichia, Enterococcus, and Clostridium, seemed to displace strict anaerobes common in the duodenum, so we refer to these taxa as disruptors. Disruptor taxa were enriched in samples with high total microbial loads and in individuals with small intestinal bacterial overgrowth (SIBO). Absolute loads of disruptors were associated with more severe GI symptoms, highlighting the value of absolute taxon quantification when studying small-intestine health and function. \n\nConclusion: This study provides the largest dataset of the absolute abundance of microbiota from the human duodenum to date. The results reveal a clear relationship between the oral microbiota and the duodenal microbiota and suggest an association between the absolute abundance of disruptor taxa, SIBO, and the prevalence of severe GI symptoms.", "date": "2021-11-02", "date_type": "published", "publication": "Microbiome", "volume": "9", "publisher": "Springer", "pagerange": "Art. No. 214", "id_number": "CaltechAUTHORS:20211110-202208524", "issn": "2049-2618", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211110-202208524", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Kenneth Rainin Foundation", "grant_number": "2018-1207" }, { "agency": "Jacobs Institute for Molecular Engineering for Medicine" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "T32GM112592" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1186/s40168-021-01162-2", "pmcid": "PMC8561862", "primary_object": { "basename": "s40168-021-01162-2.pdf", "url": "https://authors.library.caltech.edu/records/tmw0j-mph48/files/s40168-021-01162-2.pdf" }, "related_objects": [ { "basename": "40168_2021_1162_MOESM2_ESM.docx", "url": "https://authors.library.caltech.edu/records/tmw0j-mph48/files/40168_2021_1162_MOESM2_ESM.docx" }, { "basename": "40168_2021_1162_MOESM3_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/tmw0j-mph48/files/40168_2021_1162_MOESM3_ESM.xlsx" } ], "pub_year": "2021", "author_list": "Barlow, Jacob T.; Leite, Gabriela; et el." }, { "id": "https://authors.library.caltech.edu/records/24km7-q4q86", "eprint_id": 111717, "eprint_status": "archive", "datestamp": "2023-08-22 11:47:06", "lastmod": "2023-10-23 20:42:23", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Kim-Gunho", "name": { "family": "Kim", "given": "Gunho" }, "orcid": "0000-0003-1796-0908" }, { "id": "Portela-Carlos-M", "name": { "family": "Portela", "given": "Carlos M." }, "orcid": "0000-0002-2649-4235" }, { "id": "Celli-Paolo", "name": { "family": "Celli", "given": "Paolo" }, "orcid": "0000-0001-7839-7472" }, { "id": "Palermo-Antonio", "name": { "family": "Palermo", "given": "Antonio" }, "orcid": "0000-0001-9431-0461" }, { "id": "Daraio-C", "name": { "family": "Daraio", "given": "Chiara" }, "orcid": "0000-0001-5296-4440" } ] }, "title": "Poroelastic microlattices for underwater wave focusing", "ispublished": "pub", "full_text_status": "public", "keywords": "Microlattices; Acoustic metamaterials; Poroelasticity; Ultrasound; Wave focusing", "note": "\u00a9 2021 Published by Elsevier Ltd. \n\nReceived 3 June 2021, Revised 21 September 2021, Accepted 1 October 2021, Available online 14 October 2021. \n\nThis work was supported by the Rosen Center for Bioengineering, USA. Gunho Kim was funded by the Kwanjeong Educational Foundation, South Korea . GK and CD thank the founders of the Rosen center, Donna and Benjamin M. Rosen, and the president of Kwanjeong Foundation, Chonghwan Lee, for their vision and support. AP, PC and GK thank Daniel Marti Dafcik for his support during the earliest stages of this project. \n\nThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\n\nAccepted Version - 1-s2.0-S2352431621001930-main.pdf
Supplemental Material - 1-s2.0-S2352431621001930-mmc1.pdf
", "abstract": "Metamaterials with microscale architectures, e.g., microlattices, can exhibit extreme quasi-static mechanical response and tailorable acoustic properties. When coupled with pressure waves in surrounding fluid, the dynamic behavior of microlattices in the long wavelength limit can be explained in the context of Biot's theory of poroelasticity. In this work, we exploit the elastoacoustic wave propagation within 3D-printed polymeric microlattices to incorporate a gradient of refractive index for underwater ultrasonic lensing. Experimentally and numerically derived dispersion curves allow the characterization of acoustic properties of a fluid-saturated elastic lattice. A modified Luneburg lens index profile adapted for underwater wave focusing is demonstrated via the finite element method and immersion testing, showcasing a computationally efficient poroelasticity-based design approach that enables accelerated design of acoustic wave manipulation devices. Our approach can be applied to the design of acoustic metamaterials for biomedical applications featuring focused ultrasound.", "date": "2021-11", "date_type": "published", "publication": "Extreme Mechanics Letters", "volume": "49", "publisher": "Elsevier", "pagerange": "Art. No. 101499", "id_number": "CaltechAUTHORS:20211102-204833333", "issn": "2352-4316", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20211102-204833333", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Kwanjeong Educational Foundation" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1016/j.eml.2021.101499", "primary_object": { "basename": "1-s2.0-S2352431621001930-main.pdf", "url": "https://authors.library.caltech.edu/records/24km7-q4q86/files/1-s2.0-S2352431621001930-main.pdf" }, "related_objects": [ { "basename": "1-s2.0-S2352431621001930-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/24km7-q4q86/files/1-s2.0-S2352431621001930-mmc1.pdf" } ], "pub_year": "2021", "author_list": "Kim, Gunho; Portela, Carlos M.; et el." }, { "id": "https://authors.library.caltech.edu/records/s1dw8-apr33", "eprint_id": 106178, "eprint_status": "archive", "datestamp": "2023-08-22 11:16:48", "lastmod": "2023-12-22 23:33:35", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Belliveau-Nathan-M", "name": { "family": "Belliveau", "given": "Nathan M." }, "orcid": "0000-0002-1536-1963" }, { "id": "Chure-Griffin-D", "name": { "family": "Chure", "given": "Griffin" }, "orcid": "0000-0002-2216-2057" }, { "id": "Hueschen-Christina-L", "name": { "family": "Hueschen", "given": "Christina L." }, "orcid": "0000-0002-3437-2895" }, { "id": "Garcia-Hernan-G", "name": { "family": "Garcia", "given": "Hernan G." }, "orcid": "0000-0002-5212-3649" }, { "id": "Kondev-Jane", "name": { "family": "Kondev", "given": "Jane" }, "orcid": "0000-0001-7522-7144" }, { "id": "Fisher-Daniel-S", "name": { "family": "Fisher", "given": "Daniel S." } }, { "id": "Theriot-Julie-A", "name": { "family": "Theriot", "given": "Julie A." }, "orcid": "0000-0002-2334-2535" }, { "id": "Phillips-R", "name": { "family": "Phillips", "given": "Rob" }, "orcid": "0000-0003-3082-2809" } ] }, "title": "Fundamental limits on the rate of bacterial growth and their influence on proteomic composition", "ispublished": "pub", "full_text_status": "public", "keywords": "microbial physiology; proteomics; cellular growth; bacteria; cell size; order-of-magnitude estimation; physical biology; microbial growth laws", "note": "\u00a9 2021 Elsevier Inc. \n\nReceived 10 December 2020, Revised 12 April 2021, Accepted 4 June 2021, Available online 1 July 2021. \n\nWe thank Matthias Heinemann, Alexander Schmidt, and Gene-Wei Li for additional input regarding their data. We also thank all members of the Phillips, Theriot, Kondev, Garcia labs, as well as Ron Milo and Terry Hwa for useful discussions. We thank Suzannah M. Beeler, Jonas Cremer, Avi Flamholz, Soichi Hirokawa, and Manuel Razo-Mejia for reading and providing comments on drafts of this manuscript. R.P. is supported by La Fondation Pierre-Gilles de Gennes, the Rosen Center at Caltech, and the NIH 1R35 GM118043 (MIRA). J.A.T. is supported by the Howard Hughes Medical Institute, and NIH grant R37-AI036929. N.M.B is a HHMI fellow of the Jane Coffin Childs Memorial Fund. H.G.G. is supported by the Burroughs Wellcome Fund Career Award at the Scientific Interface, the Sloan Research Foundation, the Human Frontiers Science Program, the Searle Scholars Program, the Shurl & Kay Curci Foundation, the Hellman Foundation, the NIH Director's New Innovator Award (DP2 OD024541-01), and an NSF CAREER award (1652236). D.S.F. is supported by an NSF award (PHY-1607606) and the NIH (NIH R01-AI13699201). \n\nAuthor contributions: N.M.B., G.C., C.L.H., H.G.G., J.K., D.S.F., J.A.T., and R.P. conceived the project. N.M.B. and G.C. collected and analyzed data from the literature. G.C., N.M.B., and R.P. performed the order-of-magnitude estimates. R.P., J.A.T., J.K., H.G.G., and D.S.F. supervised the theoretical analyses. N.M.B., G.C., R.P., J.A.T., and C.L.H. wrote and edited the manuscript. \n\nJ.A.T. is chief scientific advisor at the Allen Institute for Cell Science (Seattle, WA, 98109). The authors otherwise declare no competing interests.\n\nAccepted Version - nihms-1714931.pdf
Submitted - 2020.10.18.344382v1.full.pdf
Supplemental Material - 1-s2.0-S240547122100209X-mmc1.pdf
Supplemental Material - 1-s2.0-S240547122100209X-mmc2.pdf
Supplemental Material - 1-s2.0-S240547122100209X-mmc3.zip
Supplemental Material - 1-s2.0-S240547122100209X-mmc4.zip
", "abstract": "Despite abundant measurements of bacterial growth rate, cell size, and protein content, we lack a rigorous understanding of what sets the scale of these quantities and when protein abundances should (or should not) depend on growth rate. Here, we estimate the basic requirements and physical constraints on steady-state growth by considering key processes in cellular physiology across a collection of Escherichia coli proteomic data covering \u22484,000 proteins and 36 growth rates. Our analysis suggests that cells are predominantly tuned for the task of cell doubling across a continuum of growth rates; specific processes do not limit growth rate or dictate cell size. We present a model of proteomic regulation as a function of nutrient supply that reconciles observed interdependences between protein synthesis, cell size, and growth rate and propose that a theoretical inability to parallelize ribosomal synthesis places a firm limit on the achievable growth rate. A record of this paper's transparent peer review process is included in the supplemental information.", "date": "2021-09-22", "date_type": "published", "publication": "Cell Systems", "volume": "12", "number": "9", "publisher": "Cell Press", "pagerange": "924-944", "id_number": "CaltechAUTHORS:20201021-080615473", "issn": "2405-4712", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201021-080615473", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "La Fondation Pierre Gilles de Gennes" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH", "grant_number": "1R35 GM118043" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH", "grant_number": "R37-AI036929" }, { "agency": "Jane Coffin Childs Memorial Fund for Medical Research" }, { "agency": "Burroughs Wellcome Fund" }, { "agency": "Alfred P. Sloan Foundation" }, { "agency": "Human Frontier Science Program" }, { "agency": "Searle Scholars Program" }, { "agency": "Shurl and Kay Curci Foundation" }, { "agency": "Hellman Foundation" }, { "agency": "NIH", "grant_number": "DP2 OD024541-01" }, { "agency": "NSF", "grant_number": "PHY-1652236" }, { "agency": "NSF", "grant_number": "PHY-1607606" }, { "agency": "NIH", "grant_number": "R01-AI13699201" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1016/j.cels.2021.06.002", "pmcid": "PMC8460600", "primary_object": { "basename": "nihms-1714931.pdf", "url": "https://authors.library.caltech.edu/records/s1dw8-apr33/files/nihms-1714931.pdf" }, "related_objects": [ { "basename": "1-s2.0-S240547122100209X-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/s1dw8-apr33/files/1-s2.0-S240547122100209X-mmc1.pdf" }, { "basename": "1-s2.0-S240547122100209X-mmc2.pdf", "url": "https://authors.library.caltech.edu/records/s1dw8-apr33/files/1-s2.0-S240547122100209X-mmc2.pdf" }, { "basename": "1-s2.0-S240547122100209X-mmc3.zip", "url": "https://authors.library.caltech.edu/records/s1dw8-apr33/files/1-s2.0-S240547122100209X-mmc3.zip" }, { "basename": "1-s2.0-S240547122100209X-mmc4.zip", "url": "https://authors.library.caltech.edu/records/s1dw8-apr33/files/1-s2.0-S240547122100209X-mmc4.zip" }, { "basename": "2020.10.18.344382v1.full.pdf", "url": "https://authors.library.caltech.edu/records/s1dw8-apr33/files/2020.10.18.344382v1.full.pdf" } ], "pub_year": "2021", "author_list": "Belliveau, Nathan M.; Chure, Griffin; et el." }, { "id": "https://authors.library.caltech.edu/records/ks7h3-tf644", "eprint_id": 106594, "eprint_status": "archive", "datestamp": "2023-08-22 10:56:38", "lastmod": "2023-12-22 23:33:01", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Qu-Zijie", "name": { "family": "Qu", "given": "Zijie" }, "orcid": "0000-0003-1500-3207" }, { "id": "Schildknecht-Dominik", "name": { "family": "Schildknecht", "given": "Dominik" }, "orcid": "0000-0002-0678-0904" }, { "id": "Shadkhoo-Shahriar", "name": { "family": "Shadkhoo", "given": "Shahriar" }, "orcid": "0000-0003-3582-0634" }, { "id": "Amaya-Enrique", "name": { "family": "Amaya", "given": "Enrique" } }, { "id": "Jiang-Jialong", "name": { "family": "Jiang", "given": "Jialong" } }, { "id": "Lee-Heun-Jin", "name": { "family": "Lee", "given": "Heun Jin" } }, { "id": "Larios-David", "name": { "family": "Larios", "given": "David" } }, { "id": "Yang-Fan", "name": { "family": "Yang", "given": "Fan" }, "orcid": "0000-0002-2248-2026" }, { "id": "Phillips-R", "name": { "family": "Phillips", "given": "Rob" }, "orcid": "0000-0003-3082-2809" }, { "id": "Thomson-M-W", "name": { "family": "Thomson", "given": "Matt" } } ] }, "title": "Persistent fluid flows defined by active matter boundaries", "ispublished": "pub", "full_text_status": "public", "keywords": "Biological physics; Fluid dynamics; Permeation and transport", "note": "\u00a9 The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. \n\nReceived 03 April 2021; Accepted 10 August 2021; Published 27 August 2021. \n\nWe acknowledge funding from the Donna and Benjamin M. Rosen Bioengineering Center, Foundational Questions Institute and Fetzer Franklin Fund (through FQXi 1816), The Moore Foundation, The Packard Foundation, and Heritage Medical Research Institute. We thank Inna-Marie Strazhnik for the preparation of figures and illustrations. We acknowledge Dr. Guy Riddihough for his editorial assistance with the paper. \n\nData availability: The data is openly available at https://doi.org/10.22002/D1.1858. \n\nCode availability: The code to reproduce our main findings can be found on the following Github repositories: The FEM code can be found on https://github.com/domischi/StokesFEM and the PIV analysis code is on https://github.com/ShaiShdk/ActiveFlow_PIV. \n\nAuthor Contributions: Z.Q., J.J., H.J.L., R.P., and M.T. conceived the project. Z.Q., H.J.L., D.L., and F.Y. performed the experiments. J.J. performed the initial investigations of the model. D.S. developed the theoretical framework and performed the finite-element simulations. S.S. performed the PIV analysis. E.A. performed the image segmentation analysis. Z.Q., D.S., and M.T. wrote the paper with input from all authors. \n\nThe authors declare no competing interests. \n\nPeer review information: Communications Physics thanks the anonymous reviewers for their contribution to the peer review of this work.\n\nPublished - s42005-021-00703-3.pdf
Submitted - 2010.08112.pdf
Supplemental Material - 42005_2021_703_MOESM10_ESM.pdf
Supplemental Material - 42005_2021_703_MOESM11_ESM.pdf
Supplemental Material - 42005_2021_703_MOESM1_ESM.pdf
Supplemental Material - 42005_2021_703_MOESM2_ESM.mov
Supplemental Material - 42005_2021_703_MOESM3_ESM.mov
Supplemental Material - 42005_2021_703_MOESM4_ESM.mov
Supplemental Material - 42005_2021_703_MOESM5_ESM.mov
Supplemental Material - 42005_2021_703_MOESM6_ESM.mov
Supplemental Material - 42005_2021_703_MOESM7_ESM.mov
Supplemental Material - 42005_2021_703_MOESM8_ESM.mov
Supplemental Material - 42005_2021_703_MOESM9_ESM.mov
", "abstract": "Biological systems control ambient fluids through the self-organization of active protein structures, including flagella, cilia, and cytoskeletal networks. Self-organization of protein components enables the control and modulation of fluid flow fields on micron scales, however, the physical principles underlying the organization and control of active-matter-driven fluid flows are poorly understood. Here, we use an optically-controlled active-matter system composed of microtubule filaments and light-switchable kinesin motor proteins to analyze the emergence of persistent flow fields. Using light, we form contractile microtubule networks of varying size and shape, and demonstrate that the geometry of microtubule flux at the corners of contracting microtubule networks predicts the architecture of fluid flow fields across network geometries through a simple point force model. Our work provides a foundation for programming microscopic fluid flows with controllable active matter and could enable the engineering of versatile and dynamic microfluidic devices.", "date": "2021-08-27", "date_type": "published", "publication": "Communications Physics", "volume": "4", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 198", "id_number": "CaltechAUTHORS:20201110-143708446", "issn": "2399-3650", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201110-143708446", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Foundational Questions Institute (FQXI)", "grant_number": "FQXi 1816" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "David and Lucile Packard Foundation" }, { "agency": "Heritage Medical Research Institute" } ] }, "local_group": { "items": [ { "id": "Heritage-Medical-Research-Institute" }, { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1038/s42005-021-00703-3", "primary_object": { "basename": "42005_2021_703_MOESM11_ESM.pdf", "url": "https://authors.library.caltech.edu/records/ks7h3-tf644/files/42005_2021_703_MOESM11_ESM.pdf" }, "related_objects": [ { "basename": "42005_2021_703_MOESM2_ESM.mov", "url": "https://authors.library.caltech.edu/records/ks7h3-tf644/files/42005_2021_703_MOESM2_ESM.mov" }, { "basename": "42005_2021_703_MOESM5_ESM.mov", "url": "https://authors.library.caltech.edu/records/ks7h3-tf644/files/42005_2021_703_MOESM5_ESM.mov" }, { "basename": "42005_2021_703_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/ks7h3-tf644/files/42005_2021_703_MOESM1_ESM.pdf" }, { "basename": "42005_2021_703_MOESM8_ESM.mov", "url": "https://authors.library.caltech.edu/records/ks7h3-tf644/files/42005_2021_703_MOESM8_ESM.mov" }, { "basename": "s42005-021-00703-3.pdf", "url": "https://authors.library.caltech.edu/records/ks7h3-tf644/files/s42005-021-00703-3.pdf" }, { "basename": "2010.08112.pdf", "url": "https://authors.library.caltech.edu/records/ks7h3-tf644/files/2010.08112.pdf" }, { "basename": "42005_2021_703_MOESM10_ESM.pdf", "url": "https://authors.library.caltech.edu/records/ks7h3-tf644/files/42005_2021_703_MOESM10_ESM.pdf" }, { "basename": "42005_2021_703_MOESM6_ESM.mov", "url": "https://authors.library.caltech.edu/records/ks7h3-tf644/files/42005_2021_703_MOESM6_ESM.mov" }, { "basename": "42005_2021_703_MOESM3_ESM.mov", "url": "https://authors.library.caltech.edu/records/ks7h3-tf644/files/42005_2021_703_MOESM3_ESM.mov" }, { "basename": "42005_2021_703_MOESM4_ESM.mov", "url": "https://authors.library.caltech.edu/records/ks7h3-tf644/files/42005_2021_703_MOESM4_ESM.mov" }, { "basename": "42005_2021_703_MOESM7_ESM.mov", "url": "https://authors.library.caltech.edu/records/ks7h3-tf644/files/42005_2021_703_MOESM7_ESM.mov" }, { "basename": "42005_2021_703_MOESM9_ESM.mov", "url": "https://authors.library.caltech.edu/records/ks7h3-tf644/files/42005_2021_703_MOESM9_ESM.mov" } ], "pub_year": "2021", "author_list": "Qu, Zijie; Schildknecht, Dominik; et el." }, { "id": "https://authors.library.caltech.edu/records/jhb0x-3mf33", "eprint_id": 109415, "eprint_status": "archive", "datestamp": "2023-08-20 03:58:08", "lastmod": "2023-12-22 23:43:10", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Tsypin-Lev-M", "name": { "family": "Tsypin", "given": "Lev M." }, "orcid": "0000-0002-0642-8468" }, { "id": "Newman-D-K", "name": { "family": "Newman", "given": "Dianne K." }, "orcid": "0000-0003-1647-1918" } ] }, "title": "Nitrate Reduction Stimulates and Is Stimulated by Phenazine-1-Carboxylic Acid Oxidation by Citrobacter portucalensis MBL", "ispublished": "pub", "full_text_status": "public", "keywords": "Citrobacter, biological oxidation, denitrification, nitrate reduction, phenazines, redox cycling", "note": "\u00a9 2021 Tsypin and Newman. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. \n\nReceived 27 July 2021; Accepted 4 August 2021; Published 31 August 2021. \n\nWe thank the members of the Newman lab, and especially Scott Saunders, Darcy McRose, Avi Flamholz, John Ciemniecki, Chelsey VanDrisse, and Justin Bois for their insight and helpful discussions throughout this work. We are grateful to Nathan Dalleska at the Water and Environment Laboratory at Caltech for training L.M.T. on the Dionex instrument and providing a facility for analytical chemistry. \n\nL.M.T. was supported by the Rosen Endowment Fellowship at Caltech and the National Science Foundation Graduate Research Fellowship (DGE\u20101745301). Additional support to D.K.N. came from NIH (1R01AI127850-01A1 and 1R01HL152190-01) and ARO (W911NF-17-1-0024) grants.\n\nPublished - mBio.02265-21.pdf
Submitted - 2021.06.04.447179v1.full.pdf
Supplemental Material - mbio.02265-21-sf001.eps
Supplemental Material - mbio.02265-21-sf002.eps
Supplemental Material - mbio.02265-21-sf003.eps
Supplemental Material - mbio.02265-21-sf004.eps
Supplemental Material - mbio.02265-21-sf005.eps
", "abstract": "Phenazines are secreted metabolites that microbes use in diverse ways, from quorum sensing to antimicrobial warfare to energy conservation. Phenazines are able to contribute to these activities due to their redox activity. The physiological consequences of cellular phenazine reduction have been extensively studied, but the counterpart phenazine oxidation has been largely overlooked. Phenazine-1-carboxylic acid (PCA) is common in the environment and readily reduced by its producers. Here, we describe its anaerobic oxidation by Citrobacter portucalensis strain MBL, which was isolated from topsoil in Falmouth, MA, and which does not produce phenazines itself. This activity depends on the availability of a suitable terminal electron acceptor, specifically nitrate. When C. portucalensis MBL is provided reduced PCA and nitrate, it oxidizes the PCA at a rate that is environmentally relevant. We compared this terminal electron acceptor-dependent PCA-oxidizing activity of C. portucalensis MBL to that of several other gammaproteobacteria with various capacities to respire nitrate. We found that PCA oxidation by these strains in a nitrate-dependent manner is decoupled from growth and strain dependent. We infer that bacterial PCA oxidation is widespread and genetically determined. Notably, oxidizing PCA enhances the rate of nitrate reduction to nitrite by C. portucalensis MBL beyond the stoichiometric exchange of electrons from PCA to nitrate, which we attribute to C. portucalensis MBL's ability to also reduce oxidized PCA, thereby catalyzing a complete PCA redox cycle. This bidirectionality highlights the versatility of PCA as a biological redox agent.", "date": "2021-07", "date_type": "published", "publication": "mBio", "volume": "12", "number": "4", "publisher": "American Society for Microbiology", "pagerange": "Art. No. e02265-21", "id_number": "CaltechAUTHORS:20210607-115053770", "issn": "2150-7511", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210607-115053770", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE\u20101745301" }, { "agency": "NIH", "grant_number": "1R01AI127850-01A1" }, { "agency": "NIH", "grant_number": "1R01HL152190-01" }, { "agency": "Army Research Office (ARO)", "grant_number": "W911NF-17-1-0024" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Geological-and-Planetary-Sciences" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1128/mBio.02265-21", "primary_object": { "basename": "2021.06.04.447179v1.full.pdf", "url": "https://authors.library.caltech.edu/records/jhb0x-3mf33/files/2021.06.04.447179v1.full.pdf" }, "related_objects": [ { "basename": "mBio.02265-21.pdf", "url": "https://authors.library.caltech.edu/records/jhb0x-3mf33/files/mBio.02265-21.pdf" }, { "basename": "mbio.02265-21-sf001.eps", "url": "https://authors.library.caltech.edu/records/jhb0x-3mf33/files/mbio.02265-21-sf001.eps" }, { "basename": "mbio.02265-21-sf002.eps", "url": "https://authors.library.caltech.edu/records/jhb0x-3mf33/files/mbio.02265-21-sf002.eps" }, { "basename": "mbio.02265-21-sf003.eps", "url": "https://authors.library.caltech.edu/records/jhb0x-3mf33/files/mbio.02265-21-sf003.eps" }, { "basename": "mbio.02265-21-sf004.eps", "url": "https://authors.library.caltech.edu/records/jhb0x-3mf33/files/mbio.02265-21-sf004.eps" }, { "basename": "mbio.02265-21-sf005.eps", "url": "https://authors.library.caltech.edu/records/jhb0x-3mf33/files/mbio.02265-21-sf005.eps" } ], "pub_year": "2021", "author_list": "Tsypin, Lev M. and Newman, Dianne K." }, { "id": "https://authors.library.caltech.edu/records/56467-ekz46", "eprint_id": 103990, "eprint_status": "archive", "datestamp": "2023-08-20 03:22:52", "lastmod": "2023-10-20 18:58:35", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Shen-Cheng", "name": { "family": "Shen", "given": "Cheng" }, "orcid": "0000-0001-7136-4715" }, { "id": "Liang-Mingshu", "name": { "family": "Liang", "given": "Mingshu" } }, { "id": "Pan-An", "name": { "family": "Pan", "given": "An" }, "orcid": "0000-0001-7710-3815" }, { "id": "Yang-Changhuei", "name": { "family": "Yang", "given": "Changhuei" }, "orcid": "0000-0001-8791-0354" } ] }, "title": "Non-iterative complex wave-field reconstruction based on Kramers\u2013Kronig relations", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2021 Chinese Laser Press. \n\nReceived 19 January 2021; revised 23 March 2021; accepted 23 March 2021; posted 25 March 2021 (Doc. ID 419886); published 24 May 2021. \n\nCheng Shen thanks Ruizhi Cao and Dr. Baptiste Blochet for helpful discussions on this work. \n\nFunding: Donna and Benjamin M. Rosen Bioengineering Center, California Institute of Technology (Rosen Center Pilot Grant Award 9900050).\n\nThe authors declare no conflicts of interest. \n\nData Availability: Data and algorithm underlying the results presented in this paper are available upon request.\n\nPublished - prj-9-6-1003.pdf
Submitted - 2005.05288.pdf
", "abstract": "A non-iterative and non-interferometric computational imaging method to reconstruct a complex wave field called synthetic aperture imaging based on Kramers\u2013Kronig relations (KKSAI) is reported. By collecting images through a modified microscope system with pupil modulation capability, we show that the phase and amplitude profile of the sample at pupil limited resolution can be extracted from as few as two intensity images by using Kramers\u2013Kronig (KK) relations. It is established that as long as each subaperture's edge crosses the pupil center, the collected raw images are mathematically analogous to off-axis holograms. This in turn allows us to adapt a recently reported KK-relations-based phase recovery framework in off-axis holography for use in KKSAI. KKSAI is non-iterative, free of parameter tuning, and applicable to a wider range of samples. Simulation and experiment results have proved that it has much lower computational burden and achieves the best reconstruction quality when compared with two existing phase imaging methods.", "date": "2021-06", "date_type": "published", "publication": "Photonics Research", "volume": "9", "number": "6", "publisher": "Optical Society of America", "pagerange": "1003-1012", "id_number": "CaltechAUTHORS:20200624-100741522", "issn": "2327-9125", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200624-100741522", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Donna and Benjamin M. Rosen Bioengineering Center", "grant_number": "9900050" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1364/PRJ.419886", "primary_object": { "basename": "2005.05288.pdf", "url": "https://authors.library.caltech.edu/records/56467-ekz46/files/2005.05288.pdf" }, "related_objects": [ { "basename": "prj-9-6-1003.pdf", "url": "https://authors.library.caltech.edu/records/56467-ekz46/files/prj-9-6-1003.pdf" } ], "pub_year": "2021", "author_list": "Shen, Cheng; Liang, Mingshu; et el." }, { "id": "https://authors.library.caltech.edu/records/a2er1-3qv71", "eprint_id": 108927, "eprint_status": "archive", "datestamp": "2023-08-20 03:19:08", "lastmod": "2023-12-22 23:33:43", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Hochrein-Lisa-M", "name": { "family": "Hochrein", "given": "Lisa M." } }, { "id": "Li-Heyun", "name": { "family": "Li", "given": "Heyun" } }, { "id": "Pierce-N-A", "name": { "family": "Pierce", "given": "Niles A." }, "orcid": "0000-0003-2367-4406" } ] }, "title": "High-Performance Allosteric Conditional Guide RNAs for Mammalian Cell-Selective Regulation of CRISPR/Cas", "ispublished": "pub", "full_text_status": "public", "keywords": "Allosteric cgRNAs, Small conditional RNAs, Dynamic RNA nanotechnology, RNA degradation, Molecular programming, Synthetic biology", "note": "\u00a9 2021 American Chemical Society. \n\nReceived: January 26, 2021; Published: April 30, 2021. \n\nWe thank Z. Chen, M. H. Hanewich-Hollatz, J. Huang, and P. W. K. Rothemund for helpful discussions. This work was funded by the Defense Advanced Research Projects Agency (HR0011-17-2-0008; the findings are those of the authors and should not be interpreted as representing the official views or policies of the U.S. Government), by the National Aeronautics and Space Administration (7000000323), by the Rosen Bioengineering Center at Caltech, by the Beckman Institute at Caltech (Programmable Molecular Technology Center, PMTC), and by a Beckman-Gray Graduate Fellowship. \n\nThe authors declare the following competing financial interest(s): Patent applications filed by the California Institute of Technology.\n\nSupplemental Material - sb1c00037_si_001.pdf
", "abstract": "The activity of a conditional guide RNA (cgRNA) is dependent on the presence or absence of an RNA trigger, enabling cell-selective regulation of CRISPR/Cas function. cgRNAs are programmable at two levels, with the target-binding sequence controlling the target of Cas activity (edit, silence, or induce a gene of choice) and the trigger-binding sequence controlling the scope of Cas activity (subset of cells expressing the trigger RNA). Allosteric cgRNA mechanisms enable independent design of the target and trigger sequences, providing the flexibility to select the regulatory target and scope independently. Building on prior advances in dynamic RNA nanotechnology that demonstrated the cgRNA concept, here we set the goal of engineering high-performance allosteric cgRNA mechanisms for the mammalian setting, pursuing both ON \u2192 OFF logic (conditional inactivation by an RNA trigger) and OFF \u2192 ON logic (conditional activation by an RNA trigger). For each mechanism, libraries of orthogonal cgRNA/trigger pairs were designed using NUPACK. In HEK 293T cells expressing cgRNAs, triggers, and inducing dCas9: (1) a library of four ON \u2192 OFF \"terminator switch\" cgRNAs exhibit a median fold-change of \u224850\u00d7, a median fractional dynamic range of \u224820%, and a median crosstalk modulus of \u22489%; (2) a library of three OFF \u2192 ON \"split-terminator switch\" cgRNAs exhibit a median fold-change of \u2248150\u00d7, a median fractional dynamic range of \u224850%, and a median crosstalk modulus of \u22484%. Further, we demonstrate that xrRNA elements that protect viral RNAs from degradation by exoribonucleases can dramatically enhance the performance of RNA synthetic biology. The high-performance allosteric cgRNAs demonstrated here for ON \u2192 OFF and OFF \u2192 ON logic in mammalian cells provide a foundation for pursuing applications of programmable cell-selective regulation.", "date": "2021-05-21", "date_type": "published", "publication": "ACS Synthetic Biology", "volume": "10", "number": "5", "publisher": "American Chemical Society", "pagerange": "964-971", "id_number": "CaltechAUTHORS:20210503-115702708", "issn": "2161-5063", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210503-115702708", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "HR0011-17-2-0008" }, { "agency": "NASA", "grant_number": "7000000323" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Caltech Beckman Institute" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1021/acssynbio.1c00037", "primary_object": { "basename": "sb1c00037_si_001.pdf", "url": "https://authors.library.caltech.edu/records/a2er1-3qv71/files/sb1c00037_si_001.pdf" }, "pub_year": "2021", "author_list": "Hochrein, Lisa M.; Li, Heyun; et el." }, { "id": "https://authors.library.caltech.edu/records/nbgy3-d7q65", "eprint_id": 108426, "eprint_status": "archive", "datestamp": "2023-08-20 02:50:22", "lastmod": "2023-10-23 17:01:43", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Buss-Marjorie-T", "name": { "family": "Buss", "given": "Marjorie T." } }, { "id": "Ramesh-Pradeep", "name": { "family": "Ramesh", "given": "Pradeep" } }, { "id": "English-Max-Atticus", "name": { "family": "English", "given": "Max Atticus" } }, { "id": "Lee-Gosselin-Audrey", "name": { "family": "Lee-Gosselin", "given": "Audrey" }, "orcid": "0000-0002-2431-2741" }, { "id": "Shapiro-M-G", "name": { "family": "Shapiro", "given": "Mikhail G." }, "orcid": "0000-0002-0291-4215" } ] }, "title": "Spatial Control of Probiotic Bacteria in the Gastrointestinal Tract Assisted by Magnetic Particles", "ispublished": "pub", "full_text_status": "public", "keywords": "biomaterials, magnetic control, magnetic particles, microbiome, probiotics", "note": "\u00a9 2021 Wiley-VCH GmbH. \n\nIssue Online: 27 April 2021; Version of Record online: 11 March 2021; Manuscript revised: 19 January 2021; Manuscript received: 01 November 2020. \n\nM.T.B. and P.R. contributed equally to this work. This work was supported by the Pew Charitable Trust, the Packard Foundation, and the Heritage Medical Research Institute. M.T.B. was supported by an NSF GRFP fellowship. P.R. was supported by a Rosen center for Bioengineering predoctoral fellowship. The authors would like to thank Dr. Said Bogatyrev and Dr. Asher Preska Steinberg for their helpful advice, the Caltech Flow Cytometry Facility for assistance with flow cytometry, and Ivetta Vorobyova for her help with the X\u2010ray CT studies. \n\nThe authors declare no conflict of interest. \n\nData Availability Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.\n\nSupplemental Material - adma202007473-sup-0001-suppmat.pdf
", "abstract": "Engineered probiotics have the potential to diagnose and treat a variety of gastrointestinal (GI) diseases. However, these exogenous bacterial agents have limited ability to effectively colonize specific regions of the GI tract due to a lack of external control over their localization and persistence. Magnetic fields are well suited to providing such control, since they freely penetrate biological tissues. However, they are difficult to apply with sufficient strength to directly manipulate magnetically labeled cells in deep tissue such as the GI tract. Here, it is demonstrated that a composite biomagnetic material consisting of microscale magnetic particles and probiotic bacteria, when orally administered and combined with an externally applied magnetic field, enables the trapping and retention of probiotic bacteria within the GI tract of mice. This technology improves the ability of these probiotic agents to accumulate at specific locations and stably colonize without antibiotic treatment. By enhancing the ability of GI\u2010targeted probiotics to be at the right place at the right time, cellular localization assisted by magnetic particles (CLAMP) adds external physical control to an important emerging class of microbial theranostics.", "date": "2021-04-28", "date_type": "published", "publication": "Advanced Materials", "volume": "33", "number": "17", "publisher": "Wiley", "pagerange": "Art. No. 2007473", "id_number": "CaltechAUTHORS:20210315-102208370", "issn": "0935-9648", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210315-102208370", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Pew Charitable Trust", "grant_number": "91127025" }, { "agency": "David and Lucile Packard Foundation" }, { "agency": "Heritage Medical Research Institute" }, { "agency": "NSF Graduate Research Fellowship" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" } ] }, "local_group": { "items": [ { "id": "Heritage-Medical-Research-Institute" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1002/adma.202007473", "primary_object": { "basename": "adma202007473-sup-0001-suppmat.pdf", "url": "https://authors.library.caltech.edu/records/nbgy3-d7q65/files/adma202007473-sup-0001-suppmat.pdf" }, "pub_year": "2021", "author_list": "Buss, Marjorie T.; Ramesh, Pradeep; et el." }, { "id": "https://authors.library.caltech.edu/records/xpcdw-5m989", "eprint_id": 107987, "eprint_status": "archive", "datestamp": "2023-08-22 09:04:48", "lastmod": "2023-10-23 16:22:59", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zheng-Guoan", "name": { "family": "Zheng", "given": "Guoan" }, "orcid": "0000-0002-4268-2690" }, { "id": "Shen-Cheng", "name": { "family": "Shen", "given": "Cheng" }, "orcid": "0000-0001-7136-4715" }, { "id": "Jiang-Shaowei", "name": { "family": "Jiang", "given": "Shaowei" } }, { "id": "Song-Pengming", "name": { "family": "Song", "given": "Pengming" } }, { "id": "Yang-Changhuei", "name": { "family": "Yang", "given": "Changhuei" }, "orcid": "0000-0001-8791-0354" } ] }, "title": "Concept, implementations and applications of Fourier ptychography", "ispublished": "pub", "full_text_status": "public", "keywords": "Biophotonics; Imaging and sensing", "note": "\u00a9 2021 Springer Nature Limited. \n\nAccepted 07 January 2021; Published 10 February 2021. \n\nG.Z. acknowledges the support of NSF 1510077, NSF 2012140 and the UConn SPARK grant. P.S. acknowledges the support of the Thermo Fisher Scientific Fellowship. C.Y. acknowledges the support of the Rosen Bioengineering Center Endowment Fund (9900050). \n\nCode availability: Example Fourier ptychography codes and datasets are available at https://github.com/SmartImagingLabUConn/Fourier-Ptychography. \n\nAuthor Contributions: G.Z. prepared the display items. S.J. prepared the initial draft of the Supplementary Note. All authors contributed to all aspects of manuscript preparation, revision and editing. \n\nThe authors declare no competing interests. \n\nPeer review information: Nature Reviews Physics thanks Ashok Veeraraghavan and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.\n\nSupplemental Material - 42254_2021_280_MOESM1_ESM.pdf
", "abstract": "The competition between resolution and the imaging field of view is a long-standing problem in traditional imaging systems \u2014 they can produce either an image of a small area with fine details or an image of a large area with coarse details. Fourier ptychography (FP) is an approach for tackling this intrinsic trade-off in imaging systems. It takes the challenge of high-throughput and high-resolution imaging from the domain of improving the physical limitations of optics to the domain of computation. It also enables post-measurement computational correction of optical aberrations. We present the basic concept of FP, compare it to related imaging modalities and then discuss experimental implementations, such as aperture-scanning FP, macroscopic camera-scanning FP, reflection mode, single-shot set-up, X-ray FP, speckle-scanning scheme and deep-learning-related implementations. Various applications of FP are discussed, including quantitative phase imaging in 2D and 3D, digital pathology, high-throughput cytometry, aberration metrology, long-range imaging and coherent X-ray nanoscopy. A collection of datasets and reconstruction codes is provided for readers interested in implementing FP themselves.", "date": "2021-03", "date_type": "published", "publication": "Nature Reviews Physics", "volume": "3", "number": "3", "publisher": "Springer Nature", "pagerange": "207-223", "id_number": "CaltechAUTHORS:20210210-120447617", "issn": "2522-5820", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210210-120447617", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CBET-1510077" }, { "agency": "NSF", "grant_number": "DMS-2012140" }, { "agency": "University of Connecticut" }, { "agency": "Thermo Fisher Scientific" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center", "grant_number": "9900050" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1038/s42254-021-00280-y", "primary_object": { "basename": "42254_2021_280_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/xpcdw-5m989/files/42254_2021_280_MOESM1_ESM.pdf" }, "pub_year": "2021", "author_list": "Zheng, Guoan; Shen, Cheng; et el." }, { "id": "https://authors.library.caltech.edu/records/1w7k5-09830", "eprint_id": 106966, "eprint_status": "archive", "datestamp": "2023-08-22 09:02:12", "lastmod": "2023-10-23 15:13:22", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Laccetti-Benjamin", "name": { "family": "Laccetti", "given": "Benjamin" }, "orcid": "0000-0002-0399-1204" }, { "id": "Kornfield-J-A", "name": { "family": "Kornfield", "given": "Julia" }, "orcid": "0000-0001-6746-8634" } ] }, "title": "Ballistic delivery of compounds to inner layers of the cornea is limited by tough mechanical properties of stromal tissue", "ispublished": "pub", "full_text_status": "public", "keywords": "Cornea; Drug-delivery; Keratoconus; Gelatin; Penetration", "note": "\u00a9 2020 Published by Elsevier. \n\nReceived 10 July 2020, Revised 19 November 2020, Accepted 29 November 2020, Available online 5 December 2020. \n\nWe would like to acknowledge Professor Alex Groisman for getting our group started with technology for ballistics research. Also, we would like to thank Professor Guruswamy Ravichandran for fruitful discussions regarding impact mechanics. \n\nWe would like to thank Sakura Finetek for funding to complete this research. Also, we would like to thank The Jacobs Institute for Molecular Medicine for funding and the Rosen Center for Bioengineering. We would also like to thank the Caltech Biotechnology Leadership Program (a pre-doctoral program focusing on Micro/Nano medicine) for their support through NIH grant T32GM112592. \n\nData availability statement: The data that support the findings of this study are available from the corresponding author upon request. \n\nCRediT authorship contribution statement: Benjamin Laccetti: Methodology, Software, Validation, Formal analysis, Investigation, Data curation, Writing - original draft, Visualization. Julia Kornfield: Conceptualization, Writing - review & editing, Supervision, Project administration, Funding acquisition. \n\nThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\n\nSupplemental Material - 1-s2.0-S1751616120307852-mmc1.docx
", "abstract": "The barrier characteristics of the cornea are interrogated using the impact of micro-particles into ex vivo porcine cornea. Using a commercial gene gun (BioRad; PDS1000), microparticles were accelerated and made to embed in target materials: either ballistic gelatin as a reference or corneal tissue. Statistical analysis of penetration of polydisperse spherical microparticles (5\u201322 \u03bcm dia.) with density of 2.5 g/cc, 4.2 g/cc, and 7.8 g/cc (soda-lime glass, barium-titanate glass and stainless steel; more limited examination of 1.1 g/cc polyethylene and 19.2 g/cc tungsten) spanned almost two decades in kinetic energy. Penetration profiles in ballistic gelatin show that the particle embedding depth is sensitive to particle size and density. In the cornea, penetration is a weak function of size and density, and the corneal stroma is an effective stopping medium for high velocity microparticles. Despite the high water content of corneal tissue (76% w/w) compared to the stratum corneum of skin (40% w/w), the resistance to penetration of the cornea is comparable to what is seen in previous research of penetration in skin tissue. Using low density polymer particles with a therapeutic agent payload, it is demonstrated that bulk material can be ballistically delivered to the central 1 cm\u00b2 of the corneal epithelium in an even layer with high bioavailability of therapeutic compound.", "date": "2021-03", "date_type": "published", "publication": "Journal of the Mechanical Behavior of Biomedical Materials", "volume": "115", "publisher": "Elsevier", "pagerange": "Art. No. 104246", "id_number": "CaltechAUTHORS:20201208-105038922", "issn": "1751-6161", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201208-105038922", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Sakura Finetek" }, { "agency": "Joseph J. Jacobs Institute for Molecular Engineering for Medicine" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "T32GM112592" } ] }, "local_group": { "items": [ { "id": "Jacobs-Institute-for-Molecular-Engineering-for-Medicine" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1016/j.jmbbm.2020.104246", "primary_object": { "basename": "1-s2.0-S1751616120307852-mmc1.docx", "url": "https://authors.library.caltech.edu/records/1w7k5-09830/files/1-s2.0-S1751616120307852-mmc1.docx" }, "pub_year": "2021", "author_list": "Laccetti, Benjamin and Kornfield, Julia" }, { "id": "https://authors.library.caltech.edu/records/rdxhn-0d521", "eprint_id": 103922, "eprint_status": "archive", "datestamp": "2023-08-20 01:26:58", "lastmod": "2023-12-22 23:43:44", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Morrison-Muir-J", "name": { "family": "Morrison", "given": "Muir" }, "orcid": "0000-0002-0768-7234" }, { "id": "Razo-Mejia-Manuel", "name": { "family": "Razo-Mejia", "given": "Manuel" }, "orcid": "0000-0002-9510-0527" }, { "id": "Phillips-R", "name": { "family": "Phillips", "given": "Rob" }, "orcid": "0000-0003-3082-2809" } ] }, "title": "Reconciling kinetic and thermodynamic models of bacterial transcription", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2021 Morrison et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. \n\nReceived: June 14, 2020; Accepted: November 28, 2020; Published: January 19, 2021. \n\nWe thank Rob Brewster for providing the raw single-molecule mRNA FISH data. We thank Justin Bois for his key support with the Bayesian inference section. We would also like to thank Griffin Chure for invaluable feedback on the manuscript. \n\nThis material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1745301 (to M.J.M.). This work was also supported by La Fondation Pierre-Gilles de Gennes, the Rosen Center at Caltech, and the NIH 5R35GM118043-05 (MIRA) to R.P. M.R.M. was supported by the Caldwell CEMI fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. \n\nAuthor Contributions: \nConceptualization: Muir Morrison, Manuel Razo-Mejia, Rob Phillips.\nFormal analysis: Muir Morrison.\nFunding acquisition: Rob Phillips.\nInvestigation: Muir Morrison.\nMethodology: Muir Morrison, Rob Phillips.\nProject administration: Muir Morrison, Manuel Razo-Mejia, Rob Phillips.\nSoftware: Muir Morrison, Manuel Razo-Mejia.\nSupervision: Muir Morrison, Manuel Razo-Mejia, Rob Phillips.\nValidation: Muir Morrison, Manuel Razo-Mejia, Rob Phillips.\nVisualization: Muir Morrison, Manuel Razo-Mejia.\nWriting \u2013 original draft: Muir Morrison, Manuel Razo-Mejia, Rob Phillips.\nWriting \u2013 review & editing: Muir Morrison, Manuel Razo-Mejia, Rob Phillips. \n\nThe authors have declared that no competing interests exist. \n\nData Availability Statement: All data and custom scripts were collected and stored using Git version control. Code for Bayesian inference and figure generation is available on the GitHub repository (https://github.com/RPGroup-PBoC/bursty_transcription).\n\nPublished - journal.pcbi.1008572.pdf
Submitted - 2020.06.13.150292v1.full.pdf
Supplemental Material - journal.pcbi.1008572.s001.pdf
", "abstract": "The study of transcription remains one of the centerpieces of modern biology with implications in settings from development to metabolism to evolution to disease. Precision measurements using a host of different techniques including fluorescence and sequencing readouts have raised the bar for what it means to quantitatively understand transcriptional regulation. In particular our understanding of the simplest genetic circuit is sufficiently refined both experimentally and theoretically that it has become possible to carefully discriminate between different conceptual pictures of how this regulatory system works. This regulatory motif, originally posited by Jacob and Monod in the 1960s, consists of a single transcriptional repressor binding to a promoter site and inhibiting transcription. In this paper, we show how seven distinct models of this so-called simple-repression motif, based both on thermodynamic and kinetic thinking, can be used to derive the predicted levels of gene expression and shed light on the often surprising past success of the thermodynamic models. These different models are then invoked to confront a variety of different data on mean, variance and full gene expression distributions, illustrating the extent to which such models can and cannot be distinguished, and suggesting a two-state model with a distribution of burst sizes as the most potent of the seven for describing the simple-repression motif.", "date": "2021-01-19", "date_type": "published", "publication": "PLOS Computational Biology", "volume": "17", "number": "1", "publisher": "Public Library of Science", "pagerange": "Art. No. e1008572", "id_number": "CaltechAUTHORS:20200615-130249775", "issn": "1553-7358", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200615-130249775", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1745301" }, { "agency": "Fondation Pierre Gilles de Gennes" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH", "grant_number": "5R35GM118043-05" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" } ] }, "local_group": { "items": [ { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1371/journal.pcbi.1008572", "pmcid": "PMC7845990", "primary_object": { "basename": "2020.06.13.150292v1.full.pdf", "url": "https://authors.library.caltech.edu/records/rdxhn-0d521/files/2020.06.13.150292v1.full.pdf" }, "related_objects": [ { "basename": "journal.pcbi.1008572.pdf", "url": "https://authors.library.caltech.edu/records/rdxhn-0d521/files/journal.pcbi.1008572.pdf" }, { "basename": "journal.pcbi.1008572.s001.pdf", "url": "https://authors.library.caltech.edu/records/rdxhn-0d521/files/journal.pcbi.1008572.s001.pdf" } ], "pub_year": "2021", "author_list": "Morrison, Muir; Razo-Mejia, Manuel; et el." }, { "id": "https://authors.library.caltech.edu/records/he0pf-p3x16", "eprint_id": 107330, "eprint_status": "archive", "datestamp": "2023-08-20 01:13:51", "lastmod": "2023-10-20 23:05:01", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Xu-Jian-EE", "name": { "family": "Xu", "given": "Jian" }, "orcid": "0000-0002-4743-2471" }, { "id": "Jahromi-Ali-K", "name": { "family": "Jahromi", "given": "Ali K." }, "orcid": "0000-0001-9205-7853" }, { "id": "Yang-Changhuei", "name": { "family": "Yang", "given": "Changhuei" }, "orcid": "0000-0001-8791-0354" } ] }, "title": "Diffusing wave spectroscopy: A unified treatment on temporal sampling and speckle ensemble methods", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2021 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). \n\nSubmitted: 22 October 2020; Accepted: 23 December 2020; Published Online: 19 January 2021. \n\nWe thank Professor Yanbei Chen for helpful discussions. This work was supported by the Rosen Bioengineering Center Endowment Fund (Grant No. 9900050). \n\nData Availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.\n\nJian Xu, Ali K. Jahromi, and Changhuei Yang, \"Erratum: \"Diffusing wave spectroscopy: A unified treatment on temporal sampling and speckle ensemble methods\" [APL Photonics 6, 016105 (2021)]\", APL Photonics 7, 059901 (2022) https://doi.org/10.1063/5.0096261;\n\nJian Xu, Ali K. Jahromi, and Changhuei Yang , \"Erratum: \"Diffusing wave spectroscopy: A unified treatment on temporal sampling and speckle ensemble methods\" [APL Photonics 6, 016105 (2021)]\", APL Photonics 6, 099901 (2021) https://doi.org/10.1063/5.0070547\n\nPublished - 5.0034576.pdf
Submitted - 2010.13979.pdf
Erratum - 5.0070547.pdf
Erratum - 5.0096261.pdf
", "abstract": "Diffusing wave spectroscopy (DWS) is a well-known set of methods to measure the temporal dynamics of dynamic samples. In DWS, dynamic samples scatter the incident coherent light, and the information of the temporal dynamics is encoded in the scattered light. To record and analyze the light signal, there exist two types of methods\u2014temporal sampling methods and speckle ensemble methods. Temporal sampling methods, including diffuse correlation spectroscopy, use one or multiple large bandwidth detectors to sample well and analyze the temporal light signal to infer the sample temporal dynamics. Speckle ensemble methods, including speckle visibility spectroscopy, use a high-pixel-count camera sensor to capture a speckle pattern and use the speckle contrast to infer sample temporal dynamics. In this paper, we theoretically and experimentally demonstrate that the decorrelation time (\u03c4) measurement accuracy or signal-to-noise ratio (SNR) of the two types of methods has a unified and similar fundamental expression based on the number of independent observables (NIO) and the photon flux. Given a time measurement duration, the NIO in temporal sampling methods is constrained by the measurement duration, while speckle ensemble methods can outperform by using simultaneous sampling channels to scale up the NIO significantly. In the case of optical brain monitoring, the interplay of these factors favors speckle ensemble methods. We illustrate that this important engineering consideration is consistent with the previous research on blood pulsatile flow measurements, where a speckle ensemble method operating at 100-fold lower photon flux than a conventional temporal sampling system can achieve a comparable SNR.", "date": "2021-01", "date_type": "published", "publication": "APL Photonics", "volume": "6", "number": "1", "publisher": "American Institute of Physics", "pagerange": "Art. No. 016105", "id_number": "CaltechAUTHORS:20210105-133437784", "issn": "2378-0967", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210105-133437784", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Donna and Benjamin M. Rosen Bioengineering Center", "grant_number": "9900050" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1063/5.0034576", "primary_object": { "basename": "2010.13979.pdf", "url": "https://authors.library.caltech.edu/records/he0pf-p3x16/files/2010.13979.pdf" }, "related_objects": [ { "basename": "5.0034576.pdf", "url": "https://authors.library.caltech.edu/records/he0pf-p3x16/files/5.0034576.pdf" }, { "basename": "5.0070547.pdf", "url": "https://authors.library.caltech.edu/records/he0pf-p3x16/files/5.0070547.pdf" }, { "basename": "5.0096261.pdf", "url": "https://authors.library.caltech.edu/records/he0pf-p3x16/files/5.0096261.pdf" } ], "pub_year": "2021", "author_list": "Xu, Jian; Jahromi, Ali K.; et el." }, { "id": "https://authors.library.caltech.edu/records/4h68q-ep636", "eprint_id": 98655, "eprint_status": "archive", "datestamp": "2023-08-20 01:10:35", "lastmod": "2023-12-22 23:34:01", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Bannon-Dylan", "name": { "family": "Bannon", "given": "Dylan" } }, { "id": "Moen-Erick", "name": { "family": "Moen", "given": "Erick" }, "orcid": "0000-0002-5947-7044" }, { "id": "Schwartz-Morgan-S", "name": { "family": "Schwartz", "given": "Morgan" }, "orcid": "0000-0001-8131-9125" }, { "id": "Borba-Enrico", "name": { "family": "Borba", "given": "Enrico" } }, { "id": "Kudo-Takamasa", "name": { "family": "Kudo", "given": "Takamasa" }, "orcid": "0000-0002-9709-5549" }, { "id": "Greenwald-Noah", "name": { "family": "Greenwald", "given": "Noah" } }, { "id": "Vijayakumar-Vibha", "name": { "family": "Vijayakumar", "given": "Vibha" } }, { "id": "Chang-Brian-T-A", "name": { "family": "Chang", "given": "Brian" } }, { "id": "Pao-Edward", "name": { "family": "Pao", "given": "Edward" } }, { "id": "Osterman-Erik", "name": { "family": "Osterman", "given": "Erik" } }, { "id": "Graf-William", "name": { "family": "Graf", "given": "William" } }, { "id": "Van-Valen-D", "name": { "family": "Van Valen", "given": "David" }, "orcid": "0000-0001-7534-7621" } ] }, "title": "DeepCell Kiosk: scaling deep learning\u2013enabled cellular image analysis with Kubernetes", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 The Author(s), under exclusive licence to Springer Nature America, Inc. 2021. \n\nReceived 15 October 2019; Accepted 23 November 2020; Published 04 January 2021. \n\nWe thank numerous colleagues including A. Anandkumar, M. Angelo, J. Bois, I. Brown, A. Butkovic, L. Cai, I. Camplisson, M. Covert, M. Elowitz, J. Freeman, C. Frick, L. Geontoro, A. Ho, K. Huang, K. C. Huang, G. Johnson, L. Keren, D. Litovitz, D. Macklin, U. Manor, S. Patel, A. Raj, N. Pelaez Restrepo, C. Pavelchek, S. Shah and M. Thomson for helpful discussions and contributing data. We gratefully acknowledge support from the Shurl and Kay Curci Foundation, the Rita Allen Foundation, the Paul Allen Family Foundation through the Allen Discovery Center at Stanford University, the Rosen Center for Bioengineering at Caltech, Google Research Cloud, Figure 8's AI For Everyone award, and a subaward from NIH U24-CA224309-01. \n\nData availability: All data that were used to generate the figures in this paper are available at https://deepcell.org/data and at https://github.com/vanvalenlab/deepcell-tf under the deepcell.datasets module. \n\nCode availability: We used Kubernetes and TensorFlow, along with the scientific computing stack for Python. A persistent deployment of the software described can be accessed at https://deepcell.org/. All source code, including version requirements and explicit usage, is under a modified Apache license and is available at https://github.com/vanvalenlab. Detailed instructions are available at https://deepcell-kiosk.readthedocs.io. \n\nAuthor Contributions: D.B., W.G. and D.V.V. conceived the project; D.B., W.G., E.O. and D.V.V. designed the software architecture; D.B., E.O. and W.G. wrote the core components of the software; D.B., E.M., M.S., E.B., V.V., B.C., E.O., W.G. and D.V.V. contributed to the code base; T.K. and E.P. collected data for annotation; E.M., M.S., N.G., D.B., W.G. and D.V.V. wrote documentation; D.B., E.M., W.G. and D.V.V. wrote the paper; D.V.V. supervised the project. \n\nCompeting interests: The authors have filed a provisional patent for the described work; the software described here is available under a modified Apache license and is free for non-commercial uses. \n\nPeer review information: Nature Methods thanks Ola Spjuth and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Rita Strack was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.\n\nBannon, D., Moen, E., Schwartz, M. et al. Publisher Correction: DeepCell Kiosk: scaling deep learning\u2013enabled cellular image analysis with Kubernetes. Nat Methods (2021). https://doi.org/10.1038/s41592-021-01059-w\n\nSubmitted - 505032v4.full.pdf
Supplemental Material - 41592_2020_1023_MOESM1_ESM.pdf
Supplemental Material - 41592_2020_1023_MOESM2_ESM.pdf
", "abstract": "Deep learning is transforming the analysis of biological images, but applying these models to large datasets remains challenging. Here we describe the DeepCell Kiosk, cloud-native software that dynamically scales deep learning workflows to accommodate large imaging datasets. To demonstrate the scalability and affordability of this software, we identified cell nuclei in 10\u2076 1-megapixel images in ~5.5\u2009h for ~US$250, with a cost below US$100 achievable depending on cluster configuration. The DeepCell Kiosk can be downloaded at https://github.com/vanvalenlab/kiosk-console; a persistent deployment is available at https://deepcell.org/.", "date": "2021-01", "date_type": "published", "publication": "Nature Methods", "volume": "18", "number": "1", "publisher": "Nature Publishing Group", "pagerange": "43-45", "id_number": "CaltechAUTHORS:20190916-101510993", "issn": "1548-7091", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190916-101510993", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Shurl and Kay Curci Foundation" }, { "agency": "Rita Allen Foundation" }, { "agency": "Paul Allen Family Foundation" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Google Research Cloud" }, { "agency": "Figure 8's AI for Everyone" }, { "agency": "NIH", "grant_number": "U24-CA224309-01" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1038/s41592-020-01023-0", "primary_object": { "basename": "41592_2020_1023_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/4h68q-ep636/files/41592_2020_1023_MOESM1_ESM.pdf" }, "related_objects": [ { "basename": "41592_2020_1023_MOESM2_ESM.pdf", "url": "https://authors.library.caltech.edu/records/4h68q-ep636/files/41592_2020_1023_MOESM2_ESM.pdf" }, { "basename": "505032v4.full.pdf", "url": "https://authors.library.caltech.edu/records/4h68q-ep636/files/505032v4.full.pdf" } ], "pub_year": "2021", "author_list": "Bannon, Dylan; Moen, Erick; et el." }, { "id": "https://authors.library.caltech.edu/records/zb2t4-acw40", "eprint_id": 104223, "eprint_status": "archive", "datestamp": "2023-08-20 00:25:37", "lastmod": "2023-10-20 19:11:16", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Wu-Zhiguang", "name": { "family": "Wu", "given": "Zhiguang" } }, { "id": "Chen-Ye", "name": { "family": "Chen", "given": "Ye" } }, { "id": "Mukasa-Daniel", "name": { "family": "Mukasa", "given": "Daniel" }, "orcid": "0000-0001-8379-3648" }, { "id": "Pak-On-Shun", "name": { "family": "Pak", "given": "On Shun" } }, { "id": "Gao-Wei", "name": { "family": "Gao", "given": "Wei" }, "orcid": "0000-0002-8503-4562" } ] }, "title": "Medical micro/nanorobots in complex media", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2020 The Royal Society of Chemistry. \n\nSubmitted 31 Mar 2020; First published\t29 Jun 2020. \n\nThis work was supported by National Science Foundation grants 1931214 (to W. G.), 1830958 and 1931292 (to O. S. P.) and the Donna and Benjamin M. Rosen Bioengineering Center at California Institute of Technology (to W. G.). \n\nConflicts of interest: There are no conflicts to declare.", "abstract": "Medical micro/nanorobots have received tremendous attention over the past decades owing to their potential to be navigated into hard-to-reach tissues for a number of biomedical applications ranging from targeted drug/gene delivery, bio-isolation, detoxification, to nanosurgery. Despite the great promise, the majority of the past demonstrations are primarily under benchtop or in vitro conditions. Many developed micro/nanoscale propulsion mechanisms are based on the assumption of a homogeneous, Newtonian environment, while realistic biological environments are substantially more complex. Moving toward practical medical use, the field of micro/nanorobotics must overcome several major challenges including propulsion through complex media (such as blood, mucus, and vitreous) as well as deep tissue imaging and control in vivo. In this review article, we summarize the recent research efforts on investigating how various complexities in biological environments impact the propulsion of micro/nanoswimmers. We also highlight the emerging technological approaches to enhance the locomotion of micro/nanorobots in complex environments. The recent demonstrations of in vivo imaging, control and therapeutic medical applications of such micro/nanorobots are introduced. We envision that continuing materials and technological innovations through interdisciplinary collaborative efforts can bring us steps closer to the fantasy of \"swallowing a surgeon\".", "date": "2020-11-21", "date_type": "published", "publication": "Chemical Society Reviews", "volume": "49", "number": "22", "publisher": "Royal Society of Chemistry", "pagerange": "8088-8112", "id_number": "CaltechAUTHORS:20200706-101709396", "issn": "0306-0012", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200706-101709396", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "CBET-1931214" }, { "agency": "NSF", "grant_number": "EFMA-1830958" }, { "agency": "NSF", "grant_number": "CBET-1931292" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1039/d0cs00309c", "pub_year": "2020", "author_list": "Wu, Zhiguang; Chen, Ye; et el." }, { "id": "https://authors.library.caltech.edu/records/41jwe-p6r62", "eprint_id": 104391, "eprint_status": "archive", "datestamp": "2023-08-22 07:04:11", "lastmod": "2023-10-20 20:24:52", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Cua-Michelle", "name": { "family": "Cua", "given": "Michelle" } }, { "id": "Martin-Daniel", "name": { "family": "Martin", "given": "Daniel" } }, { "id": "Meza-Patricia", "name": { "family": "Meza", "given": "Patricia" } }, { "id": "Torraca-Gianni", "name": { "family": "Torraca", "given": "Gianni" } }, { "id": "Pearson-Thomas", "name": { "family": "Pearson", "given": "Thomas" } }, { "id": "Cao-Shawn", "name": { "family": "Cao", "given": "Shawn" }, "orcid": "0000-0002-4366-9965" }, { "id": "Yang-Changhuei", "name": { "family": "Yang", "given": "Changhuei" }, "orcid": "0000-0001-8791-0354" } ] }, "title": "Method to Determine Syringe Silicone Oil Layer Heterogeneity and Investigation of its Impact on Product Particle Counts", "ispublished": "pub", "full_text_status": "public", "keywords": "particle size; drug delivery system(s); image analysis; imaging methods(s); injectables", "note": "\u00a9 2020 Published by Elsevier Inc. on behalf of the American Pharmacists Association. \n\nReceived 25 February 2020, Revised 7 July 2020, Accepted 7 July 2020, Available online 15 July 2020. \n\nThis work was supported by Amgen (2016740555). M. Cua acknowledges the support from the Natural Sciences and Engineering Research Council of Canada (NSERC). D. Martin acknowledges the support from the Predoctoral Biotechnology Leadership Training from the National Institute of Health (NIH 1T32GM112592) and the Donna and Benjamin M. Rosen Bioengineering Center Fund (9900050).\n\nAccepted Version - nihms-1616991.pdf
", "abstract": "Pre-filled syringes (PFSs) are commonly used for parenteral delivery of protein therapeutics. In PFSs, the inner surface of the syringe barrel is typically coated with silicone oil for lubrication. The total amount of silicone oil as well as its distribution can impact syringe functionality and particle formation. However, methods to non-destructively characterize the silicone oil distribution are limited. In this paper, we developed a method to visualize and quantify the relative distribution of silicone oil in unfilled syringes using a custom-built multi-color interferometric imaging system. We then applied the system in a preliminary study to investigate the impact of the silicone oil distribution on the number of particles formed in solution after filling and extrusion for two different types of syringes. The syringe type with significantly lower particle counts also exhibited significantly more homogeneous silicone oil distributions. Within syringe types, no significant association was found between silicone oil distribution and particle formation. Our method can be used in further studies that investigate the impact of syringe siliconization on PFS functionality and particle formation.", "date": "2020-11", "date_type": "published", "publication": "Journal of Pharmaceutical Sciences", "volume": "109", "number": "11", "publisher": "Elsevier", "pagerange": "3292-3299", "id_number": "CaltechAUTHORS:20200715-152735840", "issn": "0022-3549", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200715-152735840", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Amgen", "grant_number": "2016740555" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "1T32GM112592" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center", "grant_number": "9900050" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1016/j.xphs.2020.07.012", "pmcid": "PMC7572663", "primary_object": { "basename": "nihms-1616991.pdf", "url": "https://authors.library.caltech.edu/records/41jwe-p6r62/files/nihms-1616991.pdf" }, "pub_year": "2020", "author_list": "Cua, Michelle; Martin, Daniel; et el." }, { "id": "https://authors.library.caltech.edu/records/21m8x-s8281", "eprint_id": 106143, "eprint_status": "archive", "datestamp": "2023-08-22 06:57:32", "lastmod": "2023-10-20 23:08:05", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rabut-C", "name": { "family": "Rabut", "given": "Claire" } }, { "id": "Yoo-Sangjin", "name": { "family": "Yoo", "given": "Sangjin" }, "orcid": "0000-0002-0449-4242" }, { "id": "Hurt-R-C", "name": { "family": "Hurt", "given": "Robert C." }, "orcid": "0000-0002-4347-6901" }, { "id": "Jin-Zhiyang", "name": { "family": "Jin", "given": "Zhiyang" }, "orcid": "0000-0002-4411-6991" }, { "id": "Li-Hongyi", "name": { "family": "Li", "given": "Hongyi" }, "orcid": "0000-0001-6970-0230" }, { "id": "Guo-Hongsun", "name": { "family": "Guo", "given": "Hongsun" } }, { "id": "Ling-Bill", "name": { "family": "Ling", "given": "Bill" }, "orcid": "0000-0002-1276-7204" }, { "id": "Shapiro-M-G", "name": { "family": "Shapiro", "given": "Mikhail G." }, "orcid": "0000-0002-0291-4215" } ] }, "title": "Ultrasound Technologies for Imaging and Modulating Neural Activity", "ispublished": "pub", "full_text_status": "public", "keywords": "ultrasound; focused ultrasound; neuroscience; functional imaging; molecular imaging; neuromodulation; sonogenetics", "note": "\u00a9 2020 Elsevier Inc. \n\nAvailable online 14 October 2020. \n\nThe authors thank members of the Shapiro, Andersen, Tsao, Tanter, and Caskey laboratories for helpful discussions. C.R. is supported by the Human Frontier Science Program Cross-Disciplinary Fellowship. S.Y. is supported by the Brain and Behavior Research Foundation NARSAD Young Investigator Award. Related research in the Shapiro laboratory was supported by the National Institutes of Health (R01EB018975, UG3MH120102, U01NS099724, and RF1MH117080), the Defense Advanced Research Projects Agency (W911NF-14-1-0111 and D14AP00050), the David and Lucille Packard Foundation, the Sontag Foundation, the Burroughs Wellcome Fund, the Jacobs Institute of Molecular Engineering in Medicine, the Rosen Center for Bioengineering, the Tianqiao and Chrissy Chen Institute for Neuroscience, and the Heritage Medical Research Institute. \n\nAuthor Contributions: All authors wrote the manuscript and prepared figures. \n\nDeclaration of Interests: The California Institute of Technology owns patents and patent applications related to some of the technologies described in this article.\n\nSupplemental Material - 1-s2.0-S0896627320307030-mmc1.pdf
", "abstract": "Visualizing and perturbing neural activity on a brain-wide scale in model animals and humans is a major goal of neuroscience technology development. Established electrical and optical techniques typically break down at this scale due to inherent physical limitations. In contrast, ultrasound readily permeates the brain, and in some cases the skull, and interacts with tissue with a fundamental resolution on the order of 100 \u03bcm and 1 ms. This basic ability has motivated major efforts to harness ultrasound as a modality for large-scale brain imaging and modulation. These efforts have resulted in already-useful neuroscience tools, including high-resolution hemodynamic functional imaging, focused ultrasound neuromodulation, and local drug delivery. Furthermore, recent breakthroughs promise to connect ultrasound to neurons at the genetic level for biomolecular imaging and sonogenetic control. In this article, we review the state of the art and ongoing developments in ultrasonic neurotechnology, building from fundamental principles to current utility, open questions, and future potential.", "date": "2020-10-14", "date_type": "published", "publication": "Neuron", "volume": "108", "number": "1", "publisher": "Cell Press", "pagerange": "93-110", "id_number": "CaltechAUTHORS:20201019-101559925", "issn": "0896-6273", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201019-101559925", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Human Frontier Science Program" }, { "agency": "Brain and Behavior Research Foundation" }, { "agency": "NIH", "grant_number": "R01EB018975" }, { "agency": "NIH", "grant_number": "UG3MH120102" }, { "agency": "NIH", "grant_number": "U01NS099724" }, { "agency": "NIH", "grant_number": "RF1MH117080" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "W911NF-14-1-0111" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "D14AP00050" }, { "agency": "David and Lucille Packard Foundation" }, { "agency": "Sontag Foundation" }, { "agency": "Burroughs Wellcome Fund" }, { "agency": "Jacobs Institute for Molecular Engineering for Medicine" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Tianqiao and Chrissy Chen Institute for Neuroscience" }, { "agency": "Heritage Medical Research Institute" } ] }, "local_group": { "items": [ { "id": "Heritage-Medical-Research-Institute" }, { "id": "Rosen-Bioengineering-Center" }, { "id": "Tianqiao-and-Chrissy-Chen-Institute-for-Neuroscience" } ] }, "doi": "10.1016/j.neuron.2020.09.003", "primary_object": { "basename": "1-s2.0-S0896627320307030-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/21m8x-s8281/files/1-s2.0-S0896627320307030-mmc1.pdf" }, "pub_year": "2020", "author_list": "Rabut, Claire; Yoo, Sangjin; et el." }, { "id": "https://authors.library.caltech.edu/records/qtd0v-e8n18", "eprint_id": 100293, "eprint_status": "archive", "datestamp": "2023-08-22 06:05:40", "lastmod": "2023-12-22 23:45:18", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Saunders-Scott-H", "name": { "family": "Saunders", "given": "Scott H." }, "orcid": "0000-0003-4224-9106" }, { "id": "Tse-Edmund-Chun-Ming", "name": { "family": "Tse", "given": "Edmund C. M." }, "orcid": "0000-0002-9313-1290" }, { "id": "Yates-Matthew-D", "name": { "family": "Yates", "given": "Matthew D." }, "orcid": "0000-0003-4373-3864" }, { "id": "Jim\u00e9nez-Otero-F", "name": { "family": "Jim\u00e9nez Otero", "given": "Fernanda" }, "orcid": "0000-0003-1583-6495" }, { "id": "Trammell-Scott-A", "name": { "family": "Trammell", "given": "Scott A." }, "orcid": "0000-0002-7996-590X" }, { "id": "Stemp-Eric-D-A", "name": { "family": "Stemp", "given": "Eric D. A." }, "orcid": "0000-0003-2098-4214" }, { "id": "Barton-J-K", "name": { "family": "Barton", "given": "Jacqueline K." }, "orcid": "0000-0001-9883-1600" }, { "id": "Tender-Leonard-M", "name": { "family": "Tender", "given": "Leonard M." }, "orcid": "0000-0001-8784-991X" }, { "id": "Newman-D-K", "name": { "family": "Newman", "given": "Dianne K." }, "orcid": "0000-0003-1647-1918" } ] }, "title": "Extracellular DNA Promotes Efficient Extracellular Electron Transfer by Pyocyanin in Pseudomonas aeruginosa Biofilms", "ispublished": "pub", "full_text_status": "public", "keywords": "biofilm; phenazine; extracellular electron transfer; Pseudomonas aeruginosa; pyocyanin; extracellular DNA; biofilm matrix; bacterial metabolism; DNA charge transfer", "note": "\u00a9 2020 Elsevier Inc. \n\nReceived 12 December 2019, Revised 19 May 2020, Accepted 9 July 2020, Available online 6 August 2020. \n\nWe thank Jeanyoung Jo, Lars Dietrich, and Matthew Parsek for providing strains and the Biological Imaging Center, GPS Division Analytical Facility, and Beckman Institute Laser Resource Center at Caltech for supporting confocal imaging, SEM imaging, and time resolved spectroscopy, respectively. We also thank three anonymous reviewers for their constructive comments. This work was supported by NIH (1R01AI127850-01A1 to D.K.N. and GM126904 to J.K.B.); ARO (W911NF-17-1-0024 to D.K.N.); ONR (N0001418WX00436 to M.D.Y., S.A.T., and L.M.T.); and Rosen Bioengineering Center at Caltech (to S.H.S., D.K.N., and J.K.B.). E.C.M.T. was supported by a Croucher Foundation Research Fellowship. \n\nAuthor Contributions: Conceptualization, S.H.S., J.K.B., L.M.T., and D.K.N.; Methodology, S.H.S., E.C.M.T., M.D.Y., F.J.O., S.A.T., E.D.A.S., J.K.B., L.M.T., and D.K.N.; Formal Analysis, S.H.S. and L.M.T.; Investigation, S.H.S., E.C.M.T., M.D.Y., F.J.O., S.A.T., and E.D.A.S.; Resources, J.K.B., L.M.T., and D.K.N.; Writing \u2013 Original Draft, S.H.S. and D.K.N.; Writing \u2013 Review & Editing, S.H.S., E.C.M.T., M.D.Y., F.J.O., S.A.T., E.D.A.S., J.K.B., L.M.T., and D.K.N.; Visualization, S.H.S.; Supervision, J.K.B., L.M.T., and D.K.N.; Funding Acquisition, J.K.B., L.M.T., and D.K.N. \n\nThe authors declare no competing interests.\n\nPublished - 1-s2.0-S0092867420308710-main.pdf
Submitted - 2019.12.12.872085v1.full.pdf
Supplemental Material - media-1.pdf
", "abstract": "Redox cycling of extracellular electron shuttles can enable the metabolic activity of subpopulations within multicellular bacterial biofilms that lack direct access to electron acceptors or donors. How these shuttles catalyze extracellular electron transfer (EET) within biofilms without being lost to the environment has been a long-standing question. Here, we show that phenazines mediate efficient EET through interactions with extracellular DNA (eDNA) in Pseudomonas aeruginosa biofilms. Retention of pyocyanin (PYO) and phenazine carboxamide in the biofilm matrix is facilitated by eDNA binding. In vitro, different phenazines can exchange electrons in the presence or absence of DNA and can participate directly in redox reactions through DNA. In vivo, biofilm eDNA can also support rapid electron transfer between redox active intercalators. Together, these results establish that PYO:eDNA interactions support an efficient redox cycle with rapid EET that is faster than the rate of PYO loss from the biofilm.", "date": "2020-08-20", "date_type": "published", "publication": "Cell", "volume": "182", "number": "4", "publisher": "Cell Press", "pagerange": "919-932", "id_number": "CaltechAUTHORS:20191213-144717393", "issn": "0092-8674", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191213-144717393", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "1R01AI127850-01A1" }, { "agency": "NIH", "grant_number": "GM126904" }, { "agency": "Army Research Office (ARO)", "grant_number": "W911NF-17-1-0024" }, { "agency": "Office of Naval Research (ONR)", "grant_number": "N0001418WX00436" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Croucher Foundation" } ] }, "local_group": { "items": [ { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Geological-and-Planetary-Sciences" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1016/j.cell.2020.07.006", "pmcid": "PMC7457544", "primary_object": { "basename": "1-s2.0-S0092867420308710-main.pdf", "url": "https://authors.library.caltech.edu/records/qtd0v-e8n18/files/1-s2.0-S0092867420308710-main.pdf" }, "related_objects": [ { "basename": "2019.12.12.872085v1.full.pdf", "url": "https://authors.library.caltech.edu/records/qtd0v-e8n18/files/2019.12.12.872085v1.full.pdf" }, { "basename": "media-1.pdf", "url": "https://authors.library.caltech.edu/records/qtd0v-e8n18/files/media-1.pdf" } ], "pub_year": "2020", "author_list": "Saunders, Scott H.; Tse, Edmund C. M.; et el." }, { "id": "https://authors.library.caltech.edu/records/43wg1-fmv92", "eprint_id": 102075, "eprint_status": "archive", "datestamp": "2023-08-22 05:51:42", "lastmod": "2023-10-19 23:48:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ruan-Haowen", "name": { "family": "Ruan", "given": "Haowen" }, "orcid": "0000-0002-4917-4509" }, { "id": "Liu-Yan", "name": { "family": "Liu", "given": "Yan" }, "orcid": "0000-0002-5837-4908" }, { "id": "Xu-Jian", "name": { "family": "Xu", "given": "Jian" }, "orcid": "0000-0002-4743-2471" }, { "id": "Huang-Yujia", "name": { "family": "Huang", "given": "Yujia" }, "orcid": "0000-0001-7667-8342" }, { "id": "Yang-Changhuei", "name": { "family": "Yang", "given": "Changhuei" }, "orcid": "0000-0001-8791-0354" } ] }, "title": "Fluorescence imaging through dynamic scattering media with speckle-encoded ultrasound-modulated light correlation", "ispublished": "pub", "full_text_status": "public", "keywords": "Adaptive optics; Biophotonics; Fluorescence imaging; Imaging and sensing", "note": "\u00a9 2020 Springer Nature Limited. \n\nReceived 28 January 2020; Accepted 30 March 2020; Published 11 May 2020. \n\nThis work was supported by the Kernel\u2013Brain Research and Technologies fund (FS 13520230) and the Rosen Bioengineering Center Endowment Fund (9900050). \n\nData availability: The data that support the plots within this paper and other findings of this study are available from the corresponding authors upon reasonable request. \n\nCode availability: The code that supports the plots within this paper and other findings of this study is available from the corresponding authors upon reasonable request. \n\nAuthor Contributions: H.R. conceived the idea. H.R., Y.L. and C.Y. developed the idea and designed the experiments. Y.L. and H.R. developed the experimental protocol and set-up. Y.L. constructed the samples and conducted the imaging experiments. H.R. and Y.L. analysed the data. C.Y., J.X., H.R., Y.L. and Y.H. conducted the theoretical analysis. All authors contributed to the preparation of the manuscript. \n\nThe authors declare no competing interests.\n\nSupplemental Material - 41566_2020_630_MOESM1_ESM.pdf
", "abstract": "Fluorescence imaging is indispensable to biomedical research, and yet it remains challenging to image through dynamic scattering samples. Techniques that combine ultrasound and light as exemplified by ultrasound-assisted wavefront shaping have enabled fluorescence imaging through scattering media. However, the translation of these techniques into in vivo applications has been hindered by the lack of high-speed solutions to counter the fast speckle decorrelation of dynamic tissue. Here, we report an ultrasound-enabled optical imaging method that instead leverages the dynamic nature to perform imaging. The method utilizes the correlation between the dynamic speckle-encoded fluorescence and ultrasound-modulated light signal that originate from the same location within a sample. We image fluorescent targets with an improved resolution of \u226475\u2009\u00b5m (versus a resolution of 1.3\u2009mm with direct optical imaging) within a scattering medium with 17\u2009ms decorrelation time. This new imaging modality paves the way for fluorescence imaging in highly scattering tissue in vivo.", "date": "2020-08", "date_type": "published", "publication": "Nature Photonics", "volume": "14", "number": "8", "publisher": "Nature Publishing Group", "pagerange": "511-516", "id_number": "CaltechAUTHORS:20200324-095704695", "issn": "1749-4885", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200324-095704695", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Kernel-Brain Research and Technologies", "grant_number": "FS 13520230" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center", "grant_number": "9900050" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1038/s41566-020-0630-0", "primary_object": { "basename": "41566_2020_630_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/43wg1-fmv92/files/41566_2020_630_MOESM1_ESM.pdf" }, "pub_year": "2020", "author_list": "Ruan, Haowen; Liu, Yan; et el." }, { "id": "https://authors.library.caltech.edu/records/5mnm9-ry303", "eprint_id": 94350, "eprint_status": "archive", "datestamp": "2023-08-19 22:34:59", "lastmod": "2023-12-22 23:43:46", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Razo-Mejia-M", "name": { "family": "Razo-Mejia", "given": "Manuel" }, "orcid": "0000-0002-9510-0527" }, { "id": "Marzen-S", "name": { "family": "Marzen", "given": "Sarah" }, "orcid": "0000-0001-5386-1101" }, { "id": "Chure-G", "name": { "family": "Chure", "given": "Griffin" }, "orcid": "0000-0002-2216-2057" }, { "id": "Taubman-R", "name": { "family": "Taubman", "given": "Rachel" }, "orcid": "0000-0002-7779-5185" }, { "id": "Morrison-Muir", "name": { "family": "Morrison", "given": "Muir" }, "orcid": "0000-0002-0768-7234" }, { "id": "Phillips-R", "name": { "family": "Phillips", "given": "Rob" }, "orcid": "0000-0003-3082-2809" } ] }, "title": "First-principles prediction of the information processing capacity of a simple genetic circuit", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2020 American Physical Society. \n\nReceived 6 May 2020; revised 29 June 2020; accepted 2 July 2020; published 13 August 2020. \n\nWe would like to thank Nathan Belliveau, Michael Betancourt, William Bialek, Justin Bois, Emanuel Flores, Hernan Garcia, Alejandro Granados, Porfirio Quintero, Catherine Triandafillou, and Ned Wingreen for useful advice and discussion. We would especially like to thank Alvaro Sanchez, Ga\u0161per Tka\u010dik, and Jane Kondev for critical observations on the manuscript. We thank Rob Brewster for providing the raw mRNA FISH data for inferences, and David Drabold for advice on the maximum entropy inferences. We are grateful to Heun Jin Lee for his key support with the quantitative microscopy. This work was supported by La Fondation Pierre\u2013Gilles de Gennes, the Rosen Center at Caltech, and the NIH 5R35GM118043-05 (MIRA). M.R.M. was supported by the Caldwell CEMI fellowship.\n\nPublished - PhysRevE.102.022404.pdf
Submitted - 594325.full.pdf
Supplemental Material - ES11876_SI.pdf
", "abstract": "Given the stochastic nature of gene expression, genetically identical cells exposed to the same environmental inputs will produce different outputs. This heterogeneity has been hypothesized to have consequences for how cells are able to survive in changing environments. Recent work has explored the use of information theory as a framework to understand the accuracy with which cells can ascertain the state of their surroundings. Yet the predictive power of these approaches is limited and has not been rigorously tested using precision measurements. To that end, we generate a minimal model for a simple genetic circuit in which all parameter values for the model come from independently published data sets. We then predict the information processing capacity of the genetic circuit for a suite of biophysical parameters such as protein copy number and protein-DNA affinity. We compare these parameter-free predictions with an experimental determination of protein expression distributions and the resulting information processing capacity of E. coli cells. We find that our minimal model captures the scaling of the cell-to-cell variability in the data and the inferred information processing capacity of our simple genetic circuit up to a systematic deviation.", "date": "2020-08", "date_type": "published", "publication": "Physical Review E", "volume": "102", "number": "2", "publisher": "American Physical Society", "pagerange": "Art. No. 022404", "id_number": "CaltechAUTHORS:20190402-080512452", "issn": "2470-0045", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190402-080512452", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "La Fondation Pierre-Gilles de Gennes" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH", "grant_number": "R35GM118043-05" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" }, { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1103/PhysRevE.102.022404", "primary_object": { "basename": "594325.full.pdf", "url": "https://authors.library.caltech.edu/records/5mnm9-ry303/files/594325.full.pdf" }, "related_objects": [ { "basename": "ES11876_SI.pdf", "url": "https://authors.library.caltech.edu/records/5mnm9-ry303/files/ES11876_SI.pdf" }, { "basename": "PhysRevE.102.022404.pdf", "url": "https://authors.library.caltech.edu/records/5mnm9-ry303/files/PhysRevE.102.022404.pdf" } ], "pub_year": "2020", "author_list": "Razo-Mejia, Manuel; Marzen, Sarah; et el." }, { "id": "https://authors.library.caltech.edu/records/41xr7-92q84", "eprint_id": 99592, "eprint_status": "archive", "datestamp": "2023-08-22 05:39:29", "lastmod": "2023-12-22 23:44:10", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Quintero-Cadena-P", "name": { "family": "Quintero-Cadena", "given": "Porfirio" }, "orcid": "0000-0003-0067-5844" }, { "id": "Lenstra-T-L", "name": { "family": "Lenstra", "given": "Tineke L." }, "orcid": "0000-0002-4440-9962" }, { "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173" } ] }, "title": "RNA Pol II Length and Disorder Enable Cooperative Scaling of Transcriptional Bursting", "ispublished": "pub", "full_text_status": "public", "keywords": "transcriptional bursting; RNA Pol II; CTD length; phase separation; transcription scaling", "note": "\u00a9 2020 Elsevier Inc. \n\nReceived 30 October 2019, Revised 9 April 2020, Accepted 19 May 2020, Available online 15 June 2020. \n\nWe thank Mitchell Guttman, Matt Thomson, and members of the Sternberg laboratory for helpful discussions; Heun J. Lee, Andres Collazo, and Giada Spigolon for imaging assistance; Igor Antoshechkin and Vijaya Kumar for RNA-seq experiments; and Steven Mcknight and Masato Kato for reagents. This work was supported by the Howard Hughes Medical Institute, with which P.W.S. was an investigator; the Gordon Ross Medical Foundation and Benjamin M. Rosen graduate fellowships; the Biological Imaging Center at the Caltech Beckman Institute; and the Millard and Muriel Jacobs Genetics and Genomics Laboratory. \n\nAuthor Contributions: Conceptualization, P.Q.-C. and P.W.S.; Methodology, P.Q.-C., P.W.S., and T.L.L.; Software, P.Q.-C.; Formal Analysis, P.Q.-C. and T.L.L.; Investigation, P.Q.-C.; Data Curation, P.Q.-C.; Writing \u2013 Original Draft, P.Q.-C. and P.W.S.; Writing \u2013 Review & Editing, P.Q.-C., P.W.S., and T.L.L.; Visualization, P.Q.-C.; Supervision, P.W.S.; Funding Acquisition, P.W.S. \n\nThe authors declare no competing interests.\n\nSubmitted - 825299.full.pdf
Supplemental Material - 1-s2.0-S1097276520303506-mmc1.pdf
Supplemental Material - 1-s2.0-S1097276520303506-mmc2.csv
", "abstract": "RNA polymerase II (RNA Pol II) contains a disordered C-terminal domain (CTD) whose length enigmatically correlates with genome size. The CTD is crucial to eukaryotic transcription, yet the functional and evolutionary relevance of this variation remains unclear. Here, we investigate how CTD length and disorder influence transcription. We find that length modulates the size and frequency of transcriptional bursting. Disorder is highly conserved and facilitates CTD-CTD interactions, an ability we show is separable from protein sequence and necessary for efficient transcription. We build a data-driven quantitative model, simulations of which recapitulate experiments and support that CTD length promotes initial polymerase recruitment to the promoter and slows down its release from it and that CTD-CTD interactions enable recruitment of multiple polymerases. Our results reveal how these parameters provide access to a range of transcriptional activity, offering a new perspective for the mechanistic significance of CTD length and disorder in transcription across eukaryotes.", "date": "2020-07-16", "date_type": "published", "publication": "Molecular Cell", "volume": "79", "number": "2", "publisher": "Elsevier", "pagerange": "207-220", "id_number": "CaltechAUTHORS:20191031-131636300", "issn": "1097-2765", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191031-131636300", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Gordon Ross Medical Foundation" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Millard and Muriel Jacobs Genetics and Genomics Laboratory" } ] }, "local_group": { "items": [ { "id": "Millard-and-Muriel-Jacobs-Genetics-and-Genomics-Laboratory" }, { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1016/j.molcel.2020.05.030", "primary_object": { "basename": "825299.full.pdf", "url": "https://authors.library.caltech.edu/records/41xr7-92q84/files/825299.full.pdf" }, "related_objects": [ { "basename": "1-s2.0-S1097276520303506-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/41xr7-92q84/files/1-s2.0-S1097276520303506-mmc1.pdf" }, { "basename": "1-s2.0-S1097276520303506-mmc2.csv", "url": "https://authors.library.caltech.edu/records/41xr7-92q84/files/1-s2.0-S1097276520303506-mmc2.csv" } ], "pub_year": "2020", "author_list": "Quintero-Cadena, Porfirio; Lenstra, Tineke L.; et el." }, { "id": "https://authors.library.caltech.edu/records/6famx-f0654", "eprint_id": 101678, "eprint_status": "archive", "datestamp": "2023-08-19 21:30:45", "lastmod": "2023-12-22 23:33:07", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Barlow-Jacob-T", "name": { "family": "Barlow", "given": "Jacob T." }, "orcid": "0000-0002-1842-4835" }, { "id": "Bogatyrev-Said-R", "name": { "family": "Bogatyrev", "given": "Said R." }, "orcid": "0000-0003-0486-9451" }, { "id": "Ismagilov-R-F", "name": { "family": "Ismagilov", "given": "Rustem F." }, "orcid": "0000-0002-3680-4399" } ] }, "title": "A Quantitative Sequencing Framework for Absolute Abundance Measurements of Mucosal and Lumenal Microbial Communities", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. \n\nReceived 15 March 2020; Accepted 20 April 2020; Published 22 May 2020. \n\nThis work was supported in part by the Kenneth Rainin Foundation (2018\u20131207), the Army Research Office (ARO) Multidisciplinary University Research Initiative (MURI #W911NF-17-1-0402), and a National Institutes of Health Biotechnology Leadership Pre-doctoral Training Program (BLP) fellowship from Caltech's Donna and Benjamin M. Rosen Bioengineering Center (T32GM112592, to J.T.B.). We thank Elaine Hsiao and Christine Olson for helpful discussions and input on the experimental design and diets; we thank the Caltech Bioinformatics Resource Center for assistance with statistical analyses; we acknowledge the Caltech animal facility for experimental resources; we thank the Caltech Office of Laboratory Animal Resources and the veterinary technicians at Caltech for technical support; and Natasha Shelby for contributions to writing and editing this manuscript. \n\nData availability: The complete sequencing data generated during this study are available in the National Center for Biotechnology Information Sequence Read Archive repository under study accession number PRJNA575097. Raw data for all figures are provided as Source data file. \n\nAuthor Contributions: J.T.B. validated limits of digital PCR assay with mock microbial communities in germ-free tissues; designed, performed, and analyzed experiments to validate accuracy of quantitative sequencing with dPCR anchoring; established the quantitative limits of an individual taxon's absolute abundance; conducted the ketogenic animal study; analyzed all data; created all figures; and wrote the paper. S.R.B. co-developed the idea of quantitative sequencing with dPCR anchoring for absolute quantification of total microbial loads and taxa absolute abundances in lumenal and mucosal samples; contributed the method for quantitative sequencing with dPCR anchoring in lumenal and mucosal samples; contributed ideas and provided support for animal study design; contributed ideas for data-analysis and representation. R.F.I. contributed to study design and manuscript preparation. \n\nThe authors declare no competing interests.\n\nPublished - s41467-020-16224-6.pdf
Submitted - 2020.02.28.970087v1.full.pdf
Supplemental Material - 41467_2020_16224_MOESM1_ESM.pdf
Supplemental Material - 41467_2020_16224_MOESM2_ESM.pdf
Supplemental Material - 41467_2020_16224_MOESM3_ESM.zip
Erratum - s41467-020-17055-1.pdf
", "abstract": "A fundamental goal in microbiome studies is determining which microbes affect host physiology. Standard methods for determining changes in microbial taxa measure relative, rather than absolute abundances. Moreover, studies often analyze only stool, despite microbial diversity differing substantially among gastrointestinal (GI) locations. Here, we develop a quantitative framework to measure absolute abundances of individual bacterial taxa by combining the precision of digital PCR with the high-throughput nature of 16S rRNA gene amplicon sequencing. In a murine ketogenic-diet study, we compare microbial loads in lumenal and mucosal samples along the GI tract. Quantitative measurements of absolute (but not relative) abundances reveal decreases in total microbial loads on the ketogenic diet and enable us to determine the differential effects of diet on each taxon in stool and small-intestine mucosa samples. This rigorous quantitative microbial analysis framework, appropriate for diverse GI locations enables mapping microbial biogeography of the mammalian GI tract and more accurate analyses of changes in microbial taxa in microbiome studies.", "date": "2020-05-22", "date_type": "published", "publication": "Nature Communications", "volume": "11", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 2590", "id_number": "CaltechAUTHORS:20200303-103834329", "issn": "2041-1723", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200303-103834329", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Kenneth Rainin Foundation", "grant_number": "2018-1207" }, { "agency": "Army Research Office (ARO)", "grant_number": "W911NF-17-1-0402" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "T32GM112592" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1038/s41467-020-16224-6", "pmcid": "PMC7244552", "primary_object": { "basename": "41467_2020_16224_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/6famx-f0654/files/41467_2020_16224_MOESM1_ESM.pdf" }, "related_objects": [ { "basename": "41467_2020_16224_MOESM2_ESM.pdf", "url": "https://authors.library.caltech.edu/records/6famx-f0654/files/41467_2020_16224_MOESM2_ESM.pdf" }, { "basename": "41467_2020_16224_MOESM3_ESM.zip", "url": "https://authors.library.caltech.edu/records/6famx-f0654/files/41467_2020_16224_MOESM3_ESM.zip" }, { "basename": "s41467-020-16224-6.pdf", "url": "https://authors.library.caltech.edu/records/6famx-f0654/files/s41467-020-16224-6.pdf" }, { "basename": "s41467-020-17055-1.pdf", "url": "https://authors.library.caltech.edu/records/6famx-f0654/files/s41467-020-17055-1.pdf" }, { "basename": "2020.02.28.970087v1.full.pdf", "url": "https://authors.library.caltech.edu/records/6famx-f0654/files/2020.02.28.970087v1.full.pdf" } ], "pub_year": "2020", "author_list": "Barlow, Jacob T.; Bogatyrev, Said R.; et el." }, { "id": "https://authors.library.caltech.edu/records/zfvxt-ccc70", "eprint_id": 102576, "eprint_status": "archive", "datestamp": "2023-08-19 20:50:20", "lastmod": "2023-10-20 00:18:55", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Xu-Jian", "name": { "family": "Xu", "given": "Jian" }, "orcid": "0000-0002-4743-2471" }, { "id": "Cao-Ruizhi", "name": { "family": "Cao", "given": "Ruizhi" }, "orcid": "0000-0003-3385-446X" }, { "id": "Cua-Michelle", "name": { "family": "Cua", "given": "Michelle" } }, { "id": "Yang-Changhuei", "name": { "family": "Yang", "given": "Changhuei" }, "orcid": "0000-0001-8791-0354" } ] }, "title": "Single-shot surface 3D imaging by optical coherence factor", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2020 Optical Society of America. \n\nReceived 29 November 2019; revised 20 February 2020; accepted 21 February 2020; posted 25 February 2020 (Doc. ID 384551);\npublished 18 March 2020. \n\nWe thank Cheng Shen and Dr. Yan Liu for their help with sample preparation, and Dr. Baptiste Blochet for helpful discussions. \n\nFunding: Donna and Benjamin M. Rosen Bioengineering Center, California Institute of Technology (9900050). \n\nThe authors declare no conflicts of interest.", "abstract": "We report a single-shot three-dimensional (3D) topographical imaging method, optical coherence factor (OCF) imaging, which uses optical coherence as the contrast mechanism to acquire the surface height (z-direction) information of an object. A 4-f imaging system records the light field reflected from the surface of the object. The illumination of the imaging system comes from a laser source with the optical coherence length comparable to the depth of field (DoF) of the optical system. Off-axis holographic recording is used to retrieve the coherence factor from the interference fringes, which is then converted to z-direction information. In this experiment, we validate our 3D imaging results comparing them to axial scanning full-field optical coherence tomography images. We also analyze the contrast mechanism of OCF and show that it is able to provide additional information over conventional coherent and incoherent imaging using the same imaging setup. This single-shot computationally efficient method may have potential applications in industrial quality control inspection.", "date": "2020-04-01", "date_type": "published", "publication": "Optics Letters", "volume": "45", "number": "7", "publisher": "Optical Society of America", "pagerange": "1734-1737", "id_number": "CaltechAUTHORS:20200416-121840939", "issn": "0146-9592", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200416-121840939", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Donna and Benjamin M. Rosen Bioengineering Center", "grant_number": "9900050" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1364/ol.384551", "pub_year": "2020", "author_list": "Xu, Jian; Cao, Ruizhi; et el." }, { "id": "https://authors.library.caltech.edu/records/wpzbn-cfv90", "eprint_id": 98678, "eprint_status": "archive", "datestamp": "2023-08-22 04:28:26", "lastmod": "2023-10-18 17:33:32", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Min-Jihong", "name": { "family": "Min", "given": "Jihong" }, "orcid": "0000-0002-5788-1473" }, { "id": "Yang-Yiran", "name": { "family": "Yang", "given": "Yiran" }, "orcid": "0000-0001-8770-8746" }, { "id": "Wu-Zhiguang", "name": { "family": "Wu", "given": "Zhiguang" } }, { "id": "Gao-Wei", "name": { "family": "Gao", "given": "Wei" }, "orcid": "0000-0002-8503-4562" } ] }, "title": "Robotics in the Gut", "ispublished": "pub", "full_text_status": "restricted", "keywords": "capsule endoscopy; drug delivery; gastrointestinal tract; robotics; sensors", "note": "\u00a9 2019 Wiley\u2010VCH Verlag GmbH & Co. KGaA, Weinheim. \n\nIssue Online: 17 April 2020; Version of Record online: 17 September 2019; Manuscript revised: 13 August 2019; Manuscript received: 30 June 2019. \n\nThis work was sponsored by the startup funds from California Institute of Technology (Caltech), the Donna and Benjamin M. Rosen Bioengineering Center at Caltech, and Caltech\u2014City of Hope Biomedical Research Initiative.\n\nThe authors declare no conflict of interest.", "abstract": "Since the advent of ingestible temperature sensors and capsule endoscopes, rapid advances in electronics, robotics, nanotechnology, and material sciences have opened the door for the development of novel medical ingestible robots. The untethered robots provide direct, non\u2010invasive access to the entire gastrointestinal (GI) tract. Furthermore, the tissues, gases, and fluids of the gastrointestinal lumen contain a multitude of biomarkers indicative of gut diseases and health. Ingestible medical robots equipped with advanced imaging and sensing techniques can enable the diagnosis and monitoring of diseases, while providing a better pathophysiological understanding of gastrointestinal disorders. In addition, various robotic actuation mechanisms in the macro\u2010 and microscale can realize enhanced drug delivery and surgical interventions for the treatment of diseases. In this paper, an overview of recent advances in ingestible robots toward imaging, sensing, drug delivery, and surgical applications in the GI tract is provided. Key challenges and strategies for the development of novel ingestible robots and future directions of ingestible robots toward precision medicine are also discussed.", "date": "2020-04", "date_type": "published", "publication": "Advanced Therapeutics", "volume": "3", "number": "4", "publisher": "Wiley", "pagerange": "Art. No. 1900125", "id_number": "CaltechAUTHORS:20190917-132535911", "issn": "2366-3987", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190917-132535911", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Caltech" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Caltech-City of Hope Biomedical Initiative" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1002/adtp.201900125", "pub_year": "2020", "author_list": "Min, Jihong; Yang, Yiran; et el." }, { "id": "https://authors.library.caltech.edu/records/0tqzf-em128", "eprint_id": 101055, "eprint_status": "archive", "datestamp": "2023-08-19 20:37:28", "lastmod": "2023-10-19 22:23:59", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Davis-H-C", "name": { "family": "Davis", "given": "Hunter C." }, "orcid": "0000-0003-1655-692X" }, { "id": "Kang-Sunghwi", "name": { "family": "Kang", "given": "Sunghwi" } }, { "id": "Lee-Jae-Hyun", "name": { "family": "Lee", "given": "Jae-Hyun" } }, { "id": "Shin-Tae-Hyun", "name": { "family": "Shin", "given": "Tae-Hyun" } }, { "id": "Putterman-H", "name": { "family": "Putterman", "given": "Harry" } }, { "id": "Cheon-Jinwoo", "name": { "family": "Cheon", "given": "Jinwoo" } }, { "id": "Shapiro-M-G", "name": { "family": "Shapiro", "given": "Mikhail G." }, "orcid": "0000-0002-0291-4215" } ] }, "title": "Nanoscale Heat Transfer from Magnetic Nanoparticles and Ferritin in an Alternating Magnetic Field", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2020 Biophysical Society. \n\nReceived 11 November 2019, Accepted 21 January 2020, Available online 1 February 2020. \n\nThe authors thank Polina Anikeeva, Arnd Pralle, Michael Christiansen, George Varnavides, Pradeep Ramesh, and Markus Meister for helpful discussions and Yuxing Yao for assistance with electron microscopy. \n\nThis research was supported by the Burroughs Wellcome Career Award at the Scientific Interface, the Packard Fellowship in Science and Engineering, the Rosen Center for Bioengineering, and the Center for Environmental Microbial Interactions at Caltech. \n\nAuthor Contributions: H.C.D. and M.G.S. conceived the study. H.C.D. constructed the experimental apparatus, prepared the reagents, acquired the data, and analyzed the data. H.P. assisted in apparatus construction and data acquisition. S.K., J.-H.L., T.-H.S., and J.C. synthesized and functionalized magnetic nanoparticles. H.C.D. and M.G.S. wrote the manuscript with input from all other authors. M.G.S. supervised the research.\n\nSupplemental Material - 1-s2.0-S0006349520301016-mmc1.pdf
", "abstract": "Recent suggestions of nanoscale heat confinement on the surface of synthetic and biogenic magnetic nanoparticles during heating by radio frequency-alternating magnetic fields have generated intense interest because of the potential utility of this phenomenon for noninvasive control of biomolecular and cellular function. However, such confinement would represent a significant departure from the classical heat transfer theory. Here, we report an experimental investigation of nanoscale heat confinement on the surface of several types of iron oxide nanoparticles commonly used in biological research, using an all-optical method devoid of the potential artifacts present in previous studies. By simultaneously measuring the fluorescence of distinct thermochromic dyes attached to the particle surface or dissolved in the surrounding fluid during radio frequency magnetic stimulation, we found no measurable difference between the nanoparticle surface temperature and that of the surrounding fluid for three distinct nanoparticle types. Furthermore, the metalloprotein ferritin produced no temperature increase on the protein surface nor in the surrounding fluid. Experiments mimicking the designs of previous studies revealed potential sources of the artifacts. These findings inform the use of magnetic nanoparticle hyperthermia in engineered cellular and molecular systems.", "date": "2020-03-24", "date_type": "published", "publication": "Biophysical Journal", "volume": "118", "number": "6", "publisher": "Biophysical Society", "pagerange": "1502-1510", "id_number": "CaltechAUTHORS:20200203-092720672", "issn": "0006-3495", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200203-092720672", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Burroughs Wellcome Fund" }, { "agency": "David and Lucile Packard Foundation" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" } ] }, "local_group": { "items": [ { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1016/j.bpj.2020.01.028", "pmcid": "PMC7091488", "primary_object": { "basename": "1-s2.0-S0006349520301016-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/0tqzf-em128/files/1-s2.0-S0006349520301016-mmc1.pdf" }, "pub_year": "2020", "author_list": "Davis, Hunter C.; Kang, Sunghwi; et el." }, { "id": "https://authors.library.caltech.edu/records/q6jbr-zad07", "eprint_id": 99410, "eprint_status": "archive", "datestamp": "2023-08-22 03:03:31", "lastmod": "2023-10-18 18:17:07", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Einav-Tal", "name": { "family": "Einav", "given": "Tal" }, "orcid": "0000-0003-0777-1193" }, { "id": "Yazdi-Shahrzad", "name": { "family": "Yazdi", "given": "Shahrzad" }, "orcid": "0000-0003-1988-4320" }, { "id": "Coey-Aaaron", "name": { "family": "Coey", "given": "Aaron" } }, { "id": "Bjorkman-P-J", "name": { "family": "Bjorkman", "given": "Pamela J." }, "orcid": "0000-0002-2277-3990" }, { "id": "Phillips-R", "name": { "family": "Phillips", "given": "Rob" }, "orcid": "0000-0003-3082-2809" } ] }, "title": "Harnessing Avidity: Quantifying the Entropic and Energetic Effects of Linker Length and Rigidity for Multivalent Binding of Antibodies to HIV-1", "ispublished": "pub", "full_text_status": "public", "keywords": "HIV-1; avidity; neutralizing antibodies; statistical mechanics", "note": "\u00a9 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). \n\nReceived 22 May 2019, Revised 10 September 2019, Accepted 17 September 2019, Available online 23 October 2019. \n\nWe thank Anthony Bartolotta, Justin Bois, Jim Eisenstein, Vahe Galstyan, Peng He, Willem Kegel, David Hsieh, Giacomo Koszegi, Pankaj Mehta, Jiseon Min, Olexei Motrunich, Noah Olsman, Vahe Singh, and Richard Zhu for useful discussions; Christopher Barnes for measuring modeled 3BNC60-Env complexes; and Marta Murphy for help preparing figures. This research was supported by NIH NIAID grants 1R01AI129784 and HIVRAD P01 AI100148 (P.J.B.), the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery grant 1040753 (P.J.B.), La Fondation Pierre-Gilles de Gennes (R.P.), the Rosen Center at Caltech (R.P.), 1R35 GM118043-01 Maximizing Investigators' Research Award (MIRA), United States, and R01 GM085286 (R.P.), and a Caltech-COH Biomedical Research Initiative (P.J.B.). We thank the Burroughs Wellcome Fund for their support through the Career Award at the Scientific Interface (S.Y.) as well as for the Physiology Course at the Marine Biological Laboratory where part of this work was done. \n\nAuthor Contributions: T.E., A.P.W., R.P., and P.J.B. conceived the project. T.E., S.Y., and R.P. developed the model and performed analyses. T.E., R.P., and P.J.B. wrote the paper with input from other authors. \n\nThe authors declare no competing interests.\n\nPublished - 1-s2.0-S2405471219303151-main.pdf
Supplemental Material - 1-s2.0-S2405471219303151-mmc1.pdf
Supplemental Material - 1-s2.0-S2405471219303151-mmc2.zip
Supplemental Material - 1-s2.0-S2405471219303151-mmc3.mp4
", "abstract": "IgG antibodies increase their apparent affinities by using both of their Fabs to simultaneously attach to antigens. HIV-1 foils this strategy by having few, and highly separated, Envelope (Env) spike targets for antibodies, forcing most IgGs to bind monovalently. Here, we develop a statistical mechanics model of synthetic diFabs joined by DNA linkers of different lengths and flexibilities. This framework enables us to translate the energetic and entropic effects of the linker into the neutralization potency of a diFab. We demonstrate that the strongest neutralization potencies are predicted to require a rigid linker that optimally spans the distance between two Fab binding sites on an Env trimer and that avidity can be further boosted by incorporating more Fabs into these constructs. These results inform the design of multivalent anti-HIV-1 therapeutics that utilize avidity effects to remain potent against HIV-1 in the face of the rapid mutation of Env spikes.", "date": "2019-11-27", "date_type": "published", "publication": "Cell Systems", "volume": "9", "number": "5", "publisher": "Cell Press", "pagerange": "466-474", "id_number": "CaltechAUTHORS:20191023-142258650", "issn": "2405-4712", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191023-142258650", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "1R01AI129784" }, { "agency": "NIH", "grant_number": "P01 AI100148" }, { "agency": "Bill and Melinda Gates Foundation", "grant_number": "1040753" }, { "agency": "La Fondation Pierre-Gilles de Gennes" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH", "grant_number": "1R35 GM118043-01" }, { "agency": "NIH", "grant_number": "R01 GM085286" }, { "agency": "Caltech-City of Hope Biomedical Initiative" }, { "agency": "Burroughs Wellcome Fund" }, { "agency": "Marine Biological Laboratory" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1016/j.cels.2019.09.007", "pmcid": "PMC6892280", "primary_object": { "basename": "1-s2.0-S2405471219303151-main.pdf", "url": "https://authors.library.caltech.edu/records/q6jbr-zad07/files/1-s2.0-S2405471219303151-main.pdf" }, "related_objects": [ { "basename": "1-s2.0-S2405471219303151-mmc1.pdf", "url": "https://authors.library.caltech.edu/records/q6jbr-zad07/files/1-s2.0-S2405471219303151-mmc1.pdf" }, { "basename": "1-s2.0-S2405471219303151-mmc2.zip", "url": "https://authors.library.caltech.edu/records/q6jbr-zad07/files/1-s2.0-S2405471219303151-mmc2.zip" }, { "basename": "1-s2.0-S2405471219303151-mmc3.mp4", "url": "https://authors.library.caltech.edu/records/q6jbr-zad07/files/1-s2.0-S2405471219303151-mmc3.mp4" } ], "pub_year": "2019", "author_list": "Einav, Tal; Yazdi, Shahrzad; et el." }, { "id": "https://authors.library.caltech.edu/records/vg8sg-xdk72", "eprint_id": 99845, "eprint_status": "archive", "datestamp": "2023-08-19 18:48:38", "lastmod": "2023-10-18 18:51:24", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Song-Yu", "name": { "family": "Song", "given": "Yu" }, "orcid": "0000-0002-4185-2256" }, { "id": "Min-Jihong", "name": { "family": "Min", "given": "Jihong" }, "orcid": "0000-0002-5788-1473" }, { "id": "Gao-Wei", "name": { "family": "Gao", "given": "Wei" }, "orcid": "0000-0002-8503-4562" } ] }, "title": "Wearable and Implantable Electronics: Moving toward Precision Therapy", "ispublished": "pub", "full_text_status": "restricted", "note": "\u00a9 2019 American Chemical Society. \n\nPublished: November 14, 2019. \n\nThis work was supported by the Rothenberg Innovation Initiative (RI\u00b2) program, Donna and Benjamin M. Rosen Bioengineering Center at the California Institute of Technology (Caltech), Caltech-City of Hope Biomedical Research Initiative, and American Heart Association Grant No. 19TPA34850157 (all to W.G.). \n\nThe authors declare no competing financial interest.", "abstract": "Soft wearable and implantable electronic systems have attracted tremendous attention due to their flexibility, conformability, and biocompatibility. Such favorable features are critical for reliably monitoring key biomedical and physiological information (including both biophysical and biochemical signals) and effective treatment and management of specific chronic diseases. Miniaturized, fully integrated self-powered bioelectronic devices that can harvest energy from the human body represent promising and emerging solutions for long-term, intimate, and personalized therapies. In this Perspective, we offer a brief overview of recent advances in wearable/implantable soft electronic devices and their therapeutic applications ranging from drug delivery to tissue regeneration. We also discuss the key opportunities, challenges, and future directions in this important area needed to fulfill the vision of personalized medicine.", "date": "2019-11-26", "date_type": "published", "publication": "ACS Nano", "volume": "13", "number": "11", "publisher": "American Chemical Society", "pagerange": "12280-12286", "id_number": "CaltechAUTHORS:20191114-134816642", "issn": "1936-0851", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20191114-134816642", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Rothenberg Innovation Initiative (RI2)" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Caltech-City of Hope Biomedical Initiative" }, { "agency": "American Heart Association", "grant_number": "19TPA34850157" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1021/acsnano.9b08323", "pub_year": "2019", "author_list": "Song, Yu; Min, Jihong; et el." }, { "id": "https://authors.library.caltech.edu/records/91xgk-csy72", "eprint_id": 98147, "eprint_status": "archive", "datestamp": "2023-08-19 18:13:38", "lastmod": "2023-10-18 17:05:33", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhukov-D-V", "name": { "family": "Zhukov", "given": "Dmitriy V." }, "orcid": "0000-0002-4834-3147" }, { "id": "Khorosheva-E-M", "name": { "family": "Khorosheva", "given": "Eugenia M." }, "orcid": "0000-0003-3620-4884" }, { "id": "Khazaei-Tahmineh", "name": { "family": "Khazaei", "given": "Tahmineh" }, "orcid": "0000-0002-4743-2383" }, { "id": "Du-Wenbin", "name": { "family": "Du", "given": "Wenbin" }, "orcid": "0000-0002-7401-1410" }, { "id": "Selck-D-A", "name": { "family": "Selck", "given": "David A." } }, { "id": "Shishkin-A-A", "name": { "family": "Shishkin", "given": "Alexander A." } }, { "id": "Ismagilov-R-F", "name": { "family": "Ismagilov", "given": "Rustem F." }, "orcid": "0000-0002-3680-4399" } ] }, "title": "Microfluidic SlipChip device for multistep multiplexed biochemistry on a nanoliter scale", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 The Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. \n\nThe article was received on 06 Jun 2019, accepted on 29 Jul 2019 and first published on 23 Aug 2019. \n\nData availability: Any data not in the ESI will be made available upon request to the corresponding author. \n\nConflicts of interest: This paper is the subject of a patent application filed by Caltech. R. F. I. has a financial interest in Talis Biomedical Corp. \n\nThis research was supported in part by a seed grant from the Donna & Benjamin M. Rosen Bioengineering Center (Caltech), an NSF Graduate Research Fellowship [DGE-1144469] to D. V. Z., a Natural Sciences and Engineering Research Council of Canada (NSERC) fellowship [PGSD3-438474-2013] to T. K., an NIH Director's Pioneer Award [DP50D012190], an Achievement Rewards for College Scientists (ARCS) fellowship to D. A. S., and an NIH NRSA [5T32GM07616NSF] to D. A. S. We thank Andres Collazo at Caltech's Beckman Institute Biological Imaging Facility for imaging advice, and Igor Antoshechkin at Caltech's Millard and Muriel Jacobs Genetics and Genomics Laboratory for cDNA library sequencing. We also thank Mitchell Guttman for advice on total transcriptome sequencing, Mario Blanco and Jacob Barlow for helpful consultations on sequencing data processing, Erik B. Jue for helpful advice on 3D rendering of devices in CAD, and Natasha Shelby for contributions to writing and editing this manuscript.\n\nPublished - c9lc00541b.pdf
Supplemental Material - c9lc00541b2_si2.pdf
", "abstract": "We have developed a multistep microfluidic device that expands the current SlipChip capabilities by enabling multiple steps of droplet merging and multiplexing. Harnessing the interfacial energy between carrier and sample phases, this manually operated device accurately meters nanoliter volumes of reagents and transfers them into on-device reaction wells. Judiciously shaped microfeatures and surface-energy traps merge droplets in a parallel fashion. Wells can be tuned for different volumetric capacities and reagent types, including for pre-spotted reagents that allow for unique identification of original well contents even after their contents are pooled. We demonstrate the functionality of the multistep SlipChip by performing RNA transcript barcoding on-device for synthetic spiked-in standards and for biologically derived samples. This technology is a good candidate for a wide range of biological applications that require multiplexing of multistep reactions in nanoliter volumes, including single-cell analyses.", "date": "2019-10-07", "date_type": "published", "publication": "Lab on a Chip", "volume": "19", "number": "19", "publisher": "Royal Society of Chemistry", "pagerange": "3200-3211", "id_number": "CaltechAUTHORS:20190823-090755927", "issn": "1473-0197", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190823-090755927", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1144469" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)", "grant_number": "PGSD3-438474-2013" }, { "agency": "NIH", "grant_number": "DP50D012190" }, { "agency": "ARCS Foundation" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "5T32GM07616NSF" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1039/c9lc00541b", "primary_object": { "basename": "c9lc00541b2_si2.pdf", "url": "https://authors.library.caltech.edu/records/91xgk-csy72/files/c9lc00541b2_si2.pdf" }, "related_objects": [ { "basename": "c9lc00541b.pdf", "url": "https://authors.library.caltech.edu/records/91xgk-csy72/files/c9lc00541b.pdf" } ], "pub_year": "2019", "author_list": "Zhukov, Dmitriy V.; Khorosheva, Eugenia M.; et el." }, { "id": "https://authors.library.caltech.edu/records/e3khm-sn905", "eprint_id": 98881, "eprint_status": "archive", "datestamp": "2023-08-19 17:50:56", "lastmod": "2023-10-18 17:42:25", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ramirez-Zamora-A", "name": { "family": "Ramirez-Zamora", "given": "Adolfo" } }, { "id": "Gradinaru-V", "name": { "family": "Gradinaru", "given": "Viviana" }, "orcid": "0000-0001-5868-348X" } ] }, "title": "Proceedings of the Sixth Deep Brain Stimulation Think Tank Modulation of Brain Networks and Application of Advanced Neuroimaging, Neurophysiology, and Optogenetics", "ispublished": "pub", "full_text_status": "public", "keywords": "deep brain stimulation, neuromodulation, epilepsy, Parkinson's disease, tremor, optogenetics, Tourette syndrome, temporal dispersion", "note": "\u00a9 2019 Ramirez-Zamora, Giordano, Boyden, Gradinaru, Gunduz, Starr, Sheth, McIntyre, Fox, Vitek, Vedam-Mai, Akbar, Almeida, Bronte-Stewart, Mayberg, Pouratian, Gittis, Singer, Creed, Lazaro-Munoz, Richardson, Rossi, Cendejas-Zaragoza, D'Haese, Chiong, Gilron, Chizeck, Ko, Baker, Wagenaar, Harel, Deeb, Foote and Okun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. \n\nReceived: 05 February 2019; Accepted: 21 August 2019; Published: 12 September 2019. \n\nEthics Statement: Individual studies were approved by the local Institutional Review Board of participating institutions in this technical report and written informed consent was obtained from all participants. \n\nAuthor Contributions: AR-Z, JG, EB, VG, AG, PS, SS, CM, MF, JV, VV-M, UA, LA, HB-S, HM, NP, AHG, AS, MC, GL-M, MR, MAR, LC-Z, P-FD, WC, RG, HC, AK, KB, JW, WD, NH, WD, KF, and MO fulfilled the authorship criteria by substantial contributions to the conception of the work, providing data for the work, revisiting it critically for important intellectual content, approving the final version, and agreeing to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. \n\nConflict of Interest Statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. \n\nThe reviewer VV-V declared a past co-authorship with one of the authors MO to the handling Editor. \n\nAR-Z serves as a consultant for the National Parkinson Foundation, and has received consulting honoraria from Medtronic, Boston Scientific, and Wilson Therapeutics and has participated as a site PI and/or co-PI for several NIH, Foundation, and industry sponsored trials over the years but has not received honoraria. JG work was supported in part by the European Union's Horizon 2020 Research and Innovation Programme under grant agreement 720270: HBP SGA1; by federal funds UL1TR001409 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through the Clinical and Translational Science Awards Program (CTSA), a trademark of the Department of Health and Human Services, part of the Roadmap Initiative, \"Re-Engineering the Clinical Research Enterprise\"; by funding from the AEHS Foundation, in conjunction with Project Neuro-HOPE; and from the Austin and Ann O'Malley Visiting Chair in Bioethics of Loyola Marymount University. EB was supported by J. Doerr, the HHMI-Simons Faculty Scholars Program, the Open Philanthropy Project, Human Frontier Science Program (RGP0015/2016), US Army Research Laboratory and the US Army Research Office (W911NF1510548), US-Israel Binational Science Foundation (2014509), and NIH (2R01-DA029639 and 1R01-GM104948). VG work was primarily supported by the National Institutes of Health (NIH) Director's New Innovator grant DP2NS087949 and PECASE, National Institute on Aging grant R01AG047664, BRAIN grant U01NS090577, SPARC grant OT2OD023848-01, and the Defense Advanced Research Projects Agency (DARPA) Biological Technologies Office. Additional funding included the NSF NeuroNex Technology Hub grant 1707316 and funds from the Curci Foundation, the Beckman Institute, and the Rosen Center at Caltech. AG is supported by the NIH/NCATS Clinical and Translational Science Awards to the University of Florida UL1TR001427, KL2TR001429, and TL1TR001428. PS is a recipient of funding from the National Institutes of Health (R01 NS090913 and UH3 NS 100544) and from the Defense Advanced Research Projects Agency (DARPA). SS acknowledges support from the DARPA Restoring Active Memory (RAM) program (Co-operative Agreement N66001-14-2-4032) and NIH Grants MH104606 and 1S10OD018211-01. CM work was supported by the National Institutes of Health Grants R01 MH106173 and R01 NS086100. CM is a paid consultant for Boston Scientific Neuromodulation and Kernel, as well as a shareholder in the following companies: Surgical Information Sciences, Autonomic Technologies, Cardionomic, Enspire DBS, and Neuros Medical. MF work was supported by the NIH National Institute of Neurological Disorders and Stroke (K23NS083741) and Dystonia Medical Research Foundation. HB-S work was supported by the NINDS Grant 5 R21 NS096398-02, the Michael J. Fox Foundation, the Robert and Ruth Halperin Foundation, the John A. Blume Foundation, the Helen M. Cahill Award for Research in Parkinson's Disease, and Medtronic, Inc., who provided the devices used in this study but no additional financial support. HM work was supported by the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative (UH3NS103550) and the Hope for Depression Research Foundation. NP reports support by grants UH3NS103549, R01NS097782, and U01NS098961 from the National Institute of Neurological Disorders and Stroke (NINDS). AHG work was supported by grants from the Brain and Behavior Research Foundation (National Alliance for Research on Schizophrenia and Depression Young Investigator Grant), the Parkinson's Disease Foundation, and the NIH Intramural Research Program. MC work was funded by a Whitehall Research grant (Grant ID# 2017-12-54). GL-M work has been funded by the National Institutes of Health (NIH) grant R00HG008689. MR work has been supported by the National Institutes of Health through Grant Number UL1-TR-001857. P-FD acknowledges the National Institutes of Health (NIH) for their support of Neurotargetting LLC and their CranialSuite clinical software (R01-EB006136 and R01-NS095291). NH is a shareholder of Surgical Information Sciences, Inc. and holds a patent related to high-resolution brain image system (U.S. Patent 9600778). This study was partially supported by the National Institutes of Health (R01-NS085188, P41 EB015894, and P30 NS076408) and the University of Minnesota Udall center (P50NS098573). JW acknowledges grant support by NIH 1K01ES025436. KB reports support from NIH NINDS NS092730. AK and HC work was supported by National Institutes of Health grant T90 DA032436, National Science Foundation grant EEC-1028725, the Department of Defense through the National Defense and Engineering Graduate Fellowship program, and a donation by Medtronic. RG work was supported by NIH grants (NS090913-01 and NS100544-02) and the UC President's Postdoctoral Fellowship. MO serves as a consultant for the National Parkinson Foundation, and has received research grants from NIH, NPF, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. MO's DBS research is supported by grants R01 NR014852 and R01NS096008 from the National Institutes of Health. MO has previously received honoraria, but in the past >60 months has received no support from industry. MO has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4Patients, and Cambridge (movement disorders books). MO is an associate editor for New England Journal of Medicine Journal Watch Neurology. MO has participated in CME and educational activities on movement disorders (in the last 36 months) sponsored by PeerView, Prime, QuantiaMD, WebMD, Medicus, MedNet, Henry Stewart, and by Vanderbilt University. The institution and not MO receives grants from Medtronic, Abbvie, Allergan, and ANS/St. Jude, and the PI has no financial interest in these grants. MO has participated as a site PI and/or co-PI for several NIH, Foundation, and industry sponsored trials over the years but has not received honoraria. \n\nMO acknowledges the support of Tyler's Hope for a Dystonia Cure and the Parkinson's Foundation Center of Excellence. AS acknowledges the Packard Foundation, Friends and Alumni of Georgia Tech, and the Lane Family.\n\nPublished - fnins-13-00936.pdf
", "abstract": "The annual deep brain stimulation (DBS) Think Tank aims to create an opportunity for a multidisciplinary discussion in the field of neuromodulation to examine developments, opportunities and challenges in the field. The proceedings of the Sixth Annual Think Tank recapitulate progress in applications of neurotechnology, neurophysiology, and emerging techniques for the treatment of a range of psychiatric and neurological conditions including Parkinson's disease, essential tremor, Tourette syndrome, epilepsy, cognitive disorders, and addiction. Each section of this overview provides insight about the understanding of neuromodulation for specific disease and discusses current challenges and future directions. This year's report addresses key issues in implementing advanced neurophysiological techniques, evolving use of novel modulation techniques to deliver DBS, ans improved neuroimaging techniques. The proceedings also offer insights into the new era of brain network neuromodulation and connectomic DBS to define and target dysfunctional brain networks. The proceedings also focused on innovations in applications and understanding of adaptive DBS (closed-loop systems), the use and applications of optogenetics in the field of neurostimulation and the need to develop databases for DBS indications. Finally, updates on neuroethical, legal, social, and policy issues relevant to DBS research are discussed.", "date": "2019-09-12", "date_type": "published", "publication": "Frontiers in Neuroscience", "volume": "13", "publisher": "Frontiers", "pagerange": "Art. No. 936", "id_number": "CaltechAUTHORS:20190926-135813898", "issn": "1662-453X", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190926-135813898", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "European Research Council (ERC)", "grant_number": "720270" }, { "agency": "NIH", "grant_number": "UL1TR001409" }, { "agency": "AEHS Foundation" }, { "agency": "Loyola Marymount University" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Simons Foundation" }, { "agency": "Open Philanthropy Project" }, { "agency": "Human Frontier Science Program", "grant_number": "RGP0015/2016" }, { "agency": "Army Research Laboratory" }, { "agency": "Army Research Office (ARO)", "grant_number": "W911NF1510548" }, { "agency": "Binational Science Foundation (USA-Israel)", "grant_number": "2014509" }, { "agency": "NIH", "grant_number": "2R01-DA029639" }, { "agency": "NIH", "grant_number": "1R01-GM104948" }, { "agency": "NIH", "grant_number": "DP2NS087949" }, { "agency": "Presidential Early Career Awards for Scientists and Engineers (PECASE)" }, { "agency": "NIH", "grant_number": "R01AG047664" }, { "agency": "NIH", "grant_number": "U01NS090577" }, { "agency": "Stimulating Peripheral Activity to Relieve Conditions (SPARC)", "grant_number": "OT2OD023848-01" }, { "agency": "NSF", "grant_number": "DBI-1707316" }, { "agency": "Curci Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH", "grant_number": "UL1TR001427" }, { "agency": "NIH", "grant_number": "KL2TR001429" }, { "agency": "NIH", "grant_number": "TL1TR001428" }, { "agency": "NIH", "grant_number": "R01 NS090913" }, { "agency": "NIH", "grant_number": "UH3 NS 100544" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "N66001-14-2-4032" }, { "agency": "NIH", "grant_number": "MH104606" }, { "agency": "NIH", "grant_number": "1S10OD018211-01" }, { "agency": "NIH", "grant_number": "R01 MH106173" }, { "agency": "NIH", "grant_number": "R01 NS086100" }, { "agency": "NIH", "grant_number": "K23NS083741" }, { "agency": "Dystonia Medical Research Foundation" }, { "agency": "NIH", "grant_number": "5 R21 NS096398-02" }, { "agency": "Michael J. Fox Foundation" }, { "agency": "Robert and Ruth Halperin Foundation" }, { "agency": "John A. Blume Foundation" }, { "agency": "Helen M. Cahill Award" }, { "agency": "NIH", "grant_number": "UH3NS103550" }, { "agency": "Hope for Depression Research Foundation" }, { "agency": "NIH", "grant_number": "UH3NS103549" }, { "agency": "NIH", "grant_number": "R01NS097782" }, { "agency": "NIH", "grant_number": "U01NS098961" }, { "agency": "Brain and Behavior Research Foundation" }, { "agency": "Parkinson's Disease Foundation" }, { "agency": "Whitehall Research", "grant_number": "2017-12-54" }, { "agency": "NIH", "grant_number": "R00HG008689" }, { "agency": "NIH", "grant_number": "UL1-TR-001857" }, { "agency": "NIH", "grant_number": "R01-EB006136" }, { "agency": "NIH", "grant_number": "R01-NS095291" }, { "agency": "NIH", "grant_number": "R01-NS085188" }, { "agency": "NIH", "grant_number": "P41 EB015894" }, { "agency": "NIH", "grant_number": "P30 NS076408" }, { "agency": "University of Minnesota" }, { "agency": "NIH", "grant_number": "P50NS098573" }, { "agency": "NIH", "grant_number": "1K01ES025436" }, { "agency": "NIH", "grant_number": "NS092730" }, { "agency": "NIH", "grant_number": "T90 DA032436" }, { "agency": "NSF", "grant_number": "EEC-1028725" }, { "agency": "National Defense Science and Engineering Graduate (NDSEG) Fellowship" }, { "agency": "Medtronic Corp." }, { "agency": "NIH", "grant_number": "NS090913-01" }, { "agency": "NIH", "grant_number": "NS100544-02" }, { "agency": "University of California" }, { "agency": "National Psoriasis Foundation" }, { "agency": "Parkinson Alliance" }, { "agency": "Smallwood Foundation" }, { "agency": "Bachmann-Strauss Foundation" }, { "agency": "Tourette Syndrome Association" }, { "agency": "UF Foundation" }, { "agency": "NIH", "grant_number": "R01 NR014852" }, { "agency": "NIH", "grant_number": "R01NS096008" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.3389/fnins.2019.00936", "pmcid": "PMC6751331", "primary_object": { "basename": "fnins-13-00936.pdf", "url": "https://authors.library.caltech.edu/records/e3khm-sn905/files/fnins-13-00936.pdf" }, "pub_year": "2019", "author_list": "Ramirez-Zamora, Adolfo and Gradinaru, Viviana" }, { "id": "https://authors.library.caltech.edu/records/c9geb-11h23", "eprint_id": 98252, "eprint_status": "archive", "datestamp": "2023-08-19 17:49:26", "lastmod": "2023-10-18 17:11:55", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Chure-G", "name": { "family": "Chure", "given": "Griffin" }, "orcid": "0000-0002-2216-2057" }, { "id": "Razo-Mejia-M", "name": { "family": "Razo-Mejia", "given": "Manuel" }, "orcid": "0000-0002-9510-0527" }, { "id": "Belliveau-N-M", "name": { "family": "Belliveau", "given": "Nathan M." }, "orcid": "0000-0002-1536-1963" }, { "id": "Einav-T", "name": { "family": "Einav", "given": "Tal" }, "orcid": "0000-0003-0777-1193" }, { "id": "Kaczmarek-Z-A", "name": { "family": "Kaczmarek", "given": "Zofii A." }, "orcid": "0000-0002-4887-3121" }, { "id": "Barnes-S-L", "name": { "family": "Barnes", "given": "Stephanie L." }, "orcid": "0000-0002-5237-603X" }, { "id": "Lewis-M", "name": { "family": "Lewis", "given": "Mitchell" } }, { "id": "Phillips-R", "name": { "family": "Phillips", "given": "Rob" }, "orcid": "0000-0003-3082-2809" } ] }, "title": "Predictive shifts in free energy couple mutations to their phenotypic consequences", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY). \n\nEdited by Ned S. Wingreen, Princeton University, Princeton, NJ, and accepted by Editorial Board Member David Baker July 29, 2019 (received for review May 15, 2019). \n\nData and Code Availability: All data were collected, stored, and preserved by using the Git version control software. Code for data processing, analysis, and figure generation is available on the GitHub repository (https://github.com/rpgroup-pboc/mwc_mutants; DOI:10.5281/zenodo.3366376) or can be accessed via the paper website (https://www.rpgroup.caltech.edu/mwc_mutants/) (17). Raw flow cytometry data are stored on the CaltechDATA data repository and can be accessed via DOI 10.22002/D1.1241. \n\nWe thank Pamela Bj\u00f6rkman, Rachel Galimidi, and Priyanthi Gnanapragasam for access and training for the use of the Miltenyi Biotec MACSQuant flow cytometer. The experimental efforts first took place at the Physiology summer course at the Marine Biological Laboratory in Woods Hole, MA, operated by the University of Chicago. We thank Ambika Nadkarni and Damian Dudka for their work on the project during the course. We also thank Suzannah Beeler, Justin Bois, Robert Brewster, Soichi Hirokawa, Michael L\u00e4ssig, Heun Jin Lee, Muir Morrison, and Ned Wingreen for thoughtful advice and discussion. This work was supported by La Fondation Pierre-Gilles de Gennes; the Rosen Center at Caltech; and NIH Grants DP1 OD0002179 (Director's Pioneer Award), R01 GM085286, and 1R35 GM118043 Maximizing Investigators' Research Award (MIRA). N.M.B. was supported by a Howard Hughes Medical Institute International Student Research fellowship. \n\nAuthor contributions: G.C., M.R.-M., N.M.B., T.E., Z.A.K., S.L.B., M.L., and R.P. designed research; G.C., M.R.-M., N.M.B., T.E., Z.A.K., and S.L.B. performed research; G.C., M.R.-M., and N.M.B. analyzed data; M.L. and R.P. provided critical feedback and guidance; and G.C. and R.P. wrote the paper. \n\nThe authors declare no conflict of interest. \n\nThis article is a PNAS Direct Submission. N.S.W. is a guest editor invited by the Editorial Board. \n\nData deposition: Raw-flow cytometry files can be found on the CaltechDATA research data repository, https://data.caltech.edu/ (DOI: 10.22002/D1.1241). Processed data files and computer code used to perform all steps of the analysis are available on the project GitHub repository (https://github.com/rpgroup-pboc/mwc_mutants) and are registered with Zenodo, https://zenodo.org/ (DOI:10.5281/zenodo.3366376). All files, along with instructions on how to generate each figure, are available on the paper webpage, accessible through https://www.rpgroup.caltech.edu/mwc_mutants/. \n\nThis article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1907869116/-/DCSupplemental.\n\nPublished - 18275.full.pdf
Supplemental Material - pnas.1907869116.sapp.pdf
", "abstract": "Mutation is a critical mechanism by which evolution explores the functional landscape of proteins. Despite our ability to experimentally inflict mutations at will, it remains difficult to link sequence-level perturbations to systems-level responses. Here, we present a framework centered on measuring changes in the free energy of the system to link individual mutations in an allosteric transcriptional repressor to the parameters which govern its response. We find that the energetic effects of the mutations can be categorized into several classes which have characteristic curves as a function of the inducer concentration. We experimentally test these diagnostic predictions using the well-characterized LacI repressor of Escherichia coli, probing several mutations in the DNA binding and inducer binding domains. We find that the change in gene expression due to a point mutation can be captured by modifying only the model parameters that describe the respective domain of the wild-type protein. These parameters appear to be insulated, with mutations in the DNA binding domain altering only the DNA affinity and those in the inducer binding domain altering only the allosteric parameters. Changing these subsets of parameters tunes the free energy of the system in a way that is concordant with theoretical expectations. Finally, we show that the induction profiles and resulting free energies associated with pairwise double mutants can be predicted with quantitative accuracy given knowledge of the single mutants, providing an avenue for identifying and quantifying epistatic interactions.", "date": "2019-09-10", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "116", "number": "37", "publisher": "National Academy of Sciences", "pagerange": "18275-18284", "id_number": "CaltechAUTHORS:20190826-153157241", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190826-153157241", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "La Fondation Pierre Gilles de Gennes" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH", "grant_number": "DP1 OD0002179" }, { "agency": "NIH", "grant_number": "R01 GM085286" }, { "agency": "NIH", "grant_number": "1R35 GM118043" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1073/pnas.1907869116", "pmcid": "PMC6744869", "primary_object": { "basename": "18275.full.pdf", "url": "https://authors.library.caltech.edu/records/c9geb-11h23/files/18275.full.pdf" }, "related_objects": [ { "basename": "pnas.1907869116.sapp.pdf", "url": "https://authors.library.caltech.edu/records/c9geb-11h23/files/pnas.1907869116.sapp.pdf" } ], "pub_year": "2019", "author_list": "Chure, Griffin; Razo-Mejia, Manuel; et el." }, { "id": "https://authors.library.caltech.edu/records/q4kvd-j2b75", "eprint_id": 97142, "eprint_status": "archive", "datestamp": "2023-08-22 02:09:32", "lastmod": "2023-10-20 21:59:40", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yang-Kevin-K", "name": { "family": "Yang", "given": "Kevin K." }, "orcid": "0000-0001-9045-6826" }, { "id": "Wu-Zachary", "name": { "family": "Wu", "given": "Zachary" } }, { "id": "Arnold-F-H", "name": { "family": "Arnold", "given": "Frances H." }, "orcid": "0000-0002-4027-364X" } ] }, "title": "Machine-learning-guided directed evolution for protein engineering", "ispublished": "pub", "full_text_status": "public", "keywords": "Machine learning; Proteins", "note": "\u00a9 2019 Springer Nature Publishing AG. \n\nReceived 25 October 2018; Accepted 17 June 2019; Published 15 July 2019. \n\nThe authors thank Y. Chen, K. Johnston, B. Wittmann, and H. Yang for comments on early versions of the manuscript, as well as members of the Arnold lab, J. Bois, and Y. Yue for general advice and discussions on protein engineering and machine learning. This work was supported by the US Army Research Office Institute for Collaborative Biotechnologies (W911F-09-0001 to F.H.A.), the Donna and Benjamin M. Rosen Bioengineering Center (to K.K.Y.), and the National Science Foundation (GRF2017227007 to Z.W.). \n\nAuthor Contributions: K.K.Y., Z.W., and F.H.A. conceptualized the project. K.K.Y. wrote the manuscript with input and editing from all authors. \n\nThe authors declare no competing interests.\n\nSubmitted - 1811.10775.pdf
", "abstract": "Protein engineering through machine-learning-guided directed evolution enables the optimization of protein functions. Machine-learning approaches predict how sequence maps to function in a data-driven manner without requiring a detailed model of the underlying physics or biological pathways. Such methods accelerate directed evolution by learning from the properties of characterized variants and using that information to select sequences that are likely to exhibit improved properties. Here we introduce the steps required to build machine-learning sequence\u2013function models and to use those models to guide engineering, making recommendations at each stage. This review covers basic concepts relevant to the use of machine learning for protein engineering, as well as the current literature and applications of this engineering paradigm. We illustrate the process with two case studies. Finally, we look to future opportunities for machine learning to enable the discovery of unknown protein functions and uncover the relationship between protein sequence and function.", "date": "2019-08", "date_type": "published", "publication": "Nature Methods", "volume": "16", "number": "8", "publisher": "Nature Publishing Group", "pagerange": "687-694", "id_number": "CaltechAUTHORS:20190715-092459913", "issn": "1548-7091", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190715-092459913", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Army Research Office (ARO)", "grant_number": "W911F-09-0001" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "GRF2017227007" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1038/s41592-019-0496-6", "primary_object": { "basename": "1811.10775.pdf", "url": "https://authors.library.caltech.edu/records/q4kvd-j2b75/files/1811.10775.pdf" }, "pub_year": "2019", "author_list": "Yang, Kevin K.; Wu, Zachary; et el." }, { "id": "https://authors.library.caltech.edu/records/x8rgk-9ze64", "eprint_id": 92430, "eprint_status": "archive", "datestamp": "2023-08-19 16:50:14", "lastmod": "2023-10-20 22:05:08", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Hanewich-Hollatz-Mikhail-H", "name": { "family": "Hanewich-Hollatz", "given": "Mikhail H." } }, { "id": "Chen-Zhewei", "name": { "family": "Chen", "given": "Zhewei" } }, { "id": "Hochrein-Lisa-M", "name": { "family": "Hochrein", "given": "Lisa M." } }, { "id": "Huang-Jining", "name": { "family": "Huang", "given": "Jining" } }, { "id": "Pierce-N-A", "name": { "family": "Pierce", "given": "Niles A." }, "orcid": "0000-0003-2367-4406" } ] }, "title": "Conditional Guide RNAs: Programmable Conditional Regulation of CRISPR/Cas Function in Bacterial and Mammalian Cells via Dynamic RNA Nanotechnology", "ispublished": "pub", "full_text_status": "public", "keywords": "small conditional RNA (scRNA), programmable conditional regulators, allosteric regulators, CRISPR/Cas, dynamic RNA nanotechnology, molecular programming", "note": "\u00a9 2019 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: April 3, 2019; Published: June 4, 2019. \n\nWe thank S. Qi for the gift of E. coli expressing mRFP and sfGFP, N. J. Porubsky for assistance with reaction pathway engineering using NUPACK, J. S. Bois for discussions on data analysis, A. Hou and J. Kishi for performing preliminary studies, and R. Phillips for discussions on allosteric regulation. This work was funded by the Defense Advanced Research Projects Agency (HR0011-17-2-0008; the findings are those of the authors and should not be interpreted as representing the official views or policies of the US Government), by the Caltech Center for Environmental Microbial Interactions (CEMI), by the National Institutes of Health (5T32GM112592), by the Rosen Bioengineering Center at Caltech, by the Natural Sciences and Engineering Research Council (NSERC) of Canada, by the National Science Foundation Molecular Programming Project (NSF-CCF-1317694), by a Professorial Fellowship at Balliol College (University of Oxford), and by the Eastman Visiting Professorship at the University of Oxford. \n\nAuthor Contributions: M.H.H.-H. and Z.C. contributed equally. cgRNA project conceived by N.A.P. cgRNA mechanism invention by all coauthors. Exploratory mechanism studies by M.H.H.-H., Z.C., and J.H. in bacteria. Computational sequence design by M.H.H.-H. (splinted switch and toehold switch for bacteria, terminator switch for mammalian) and Z.C. (terminator switch for bacteria). Experimental design and data presentation approach developed by all coauthors. Presented cgRNA mechanisms prototyped and optimized in bacteria by Z.C. (terminator switch and toehold switch) and M.H.H.-H. (splinted switch and toehold switch), extended to mammalian cells by L.M.H. (terminator switch). Final data collected by M.H.H.-H. (bacterial) and L.M.H. (mammalian). Paper written by M.H.H.-H. and N.A.P. Supporting Information written by M.H.H.-H., L.M.H., and N.A.P. Paper edited and approved by all coauthors. \n\nThe authors declare the following competing financial interest(s): Filed patents.\n\nPublished - acscentsci.9b00340.pdf
Submitted - 525857.full.pdf
Supplemental Material - oc9b00340_si_001.pdf
", "abstract": "A guide RNA (gRNA) directs the function of a CRISPR protein effector to a target gene of choice, providing a versatile programmable platform for engineering diverse modes of synthetic regulation (edit, silence, induce, bind). However, the fact that gRNAs are constitutively active places limitations on the ability to confine gRNA activity to a desired location and time. To achieve programmable control over the scope of gRNA activity, here we apply principles from dynamic RNA nanotechnology to engineer conditional guide RNAs (cgRNAs) whose activity is dependent on the presence or absence of an RNA trigger. These cgRNAs are programmable at two levels, with the trigger-binding sequence controlling the scope of the effector activity and the target-binding sequence determining the subject of the effector activity. We demonstrate molecular mechanisms for both constitutively active cgRNAs that are conditionally inactivated by an RNA trigger (ON \u2192 OFF logic) and constitutively inactive cgRNAs that are conditionally activated by an RNA trigger (OFF \u2192 ON logic). For each mechanism, automated sequence design is performed using the reaction pathway designer within NUPACK to design an orthogonal library of three cgRNAs that respond to different RNA triggers. In E. coli expressing cgRNAs, triggers, and silencing dCas9 as the protein effector, we observe a median conditional response of \u22484-fold for an ON \u2192 OFF \"terminator switch\" mechanism, \u224815-fold for an ON \u2192 OFF \"splinted switch\" mechanism, and \u22483-fold for an OFF \u2192 ON \"toehold switch\" mechanism; the median crosstalk within each cgRNA/trigger library is <2%, \u22482%, and \u224820% for the three mechanisms. To test the portability of cgRNA mechanisms prototyped in bacteria to mammalian cells, as well as to test generalizability to different effector functions, we implemented the terminator switch in HEK 293T cells expressing inducing dCas9 as the protein effector, observing a median ON \u2192 OFF conditional response of \u22484-fold with median crosstalk of \u224830% for three orthogonal cgRNA/trigger pairs. By providing programmable control over both the scope and target of protein effector function, cgRNA regulators offer a promising platform for synthetic biology.", "date": "2019-07-24", "date_type": "published", "publication": "ACS Central Science", "volume": "5", "number": "7", "publisher": "American Chemical Society", "pagerange": "1241-1249", "id_number": "CaltechAUTHORS:20190123-124341981", "issn": "2374-7943", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190123-124341981", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "HR0011-17-2-0008" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "5T32GM112592" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Natural Sciences and Engineering Research Council (NSERC)" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "University of Oxford" } ] }, "local_group": { "items": [ { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1021/acscentsci.9b00340", "pmcid": "PMC6661866", "primary_object": { "basename": "525857.full.pdf", "url": "https://authors.library.caltech.edu/records/x8rgk-9ze64/files/525857.full.pdf" }, "related_objects": [ { "basename": "acscentsci.9b00340.pdf", "url": "https://authors.library.caltech.edu/records/x8rgk-9ze64/files/acscentsci.9b00340.pdf" }, { "basename": "oc9b00340_si_001.pdf", "url": "https://authors.library.caltech.edu/records/x8rgk-9ze64/files/oc9b00340_si_001.pdf" } ], "pub_year": "2019", "author_list": "Hanewich-Hollatz, Mikhail H.; Chen, Zhewei; et el." }, { "id": "https://authors.library.caltech.edu/records/0jam3-d5733", "eprint_id": 97391, "eprint_status": "archive", "datestamp": "2023-08-19 16:51:23", "lastmod": "2023-10-20 22:17:55", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Wu-Zhiguang", "name": { "family": "Wu", "given": "Zhiguang" } }, { "id": "Li-Lei", "name": { "family": "Li", "given": "Lei" }, "orcid": "0000-0001-6164-2646" }, { "id": "Yang-Yiran", "name": { "family": "Yang", "given": "Yiran" }, "orcid": "0000-0001-8770-8746" }, { "id": "Hu-Peng", "name": { "family": "Hu", "given": "Peng" }, "orcid": "0000-0002-2933-1239" }, { "id": "Li-Yang", "name": { "family": "Li", "given": "Yang" }, "orcid": "0000-0002-4939-8174" }, { "id": "Yang-So-Yoon", "name": { "family": "Yang", "given": "So-Yoon" } }, { "id": "Wang-Lihong-V", "name": { "family": "Wang", "given": "Lihong V." }, "orcid": "0000-0001-9783-4383" }, { "id": "Gao-Wei", "name": { "family": "Gao", "given": "Wei" }, "orcid": "0000-0002-8503-4562" } ] }, "title": "A microrobotic system guided by photoacoustic computed tomography for targeted navigation in intestines in vivo", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 The Authors, some rights reserved; exclusive licensee\nAmerican Association for the Advancement of Science. No claim\nto original U.S. Government Works. This is an article distributed under the terms of the Science Journals Default License. \n\nSubmitted 22 April 2019; Accepted 19 June 2019; Published 24 July 2019. \n\nThis work was sponsored by the Startup funds from California Institute of Technology (to W.G.), the Donna and Benjamin M. Rosen Bioengineering Center (to W.G. and L.V.W.), and the NIH grants CA186567 (NIH Director's Transformative Research Award), NS090579, and NS099717 (all to L.V.W.). We gratefully acknowledge critical support and infrastructure provided for this work by the Kavli Nanoscience Institute at Caltech. \n\nAuthor contributions: W.G. and L.V.W. conceived the project. W.G. and L.V.W. supervised the studies. Z.W., Y.Y., and S.-Y.Y. prepared and characterized the micromotors and MCs. L.L. and Z.W. performed PA experiments. Y.L. drew the schematic illustrations. L.L., P.H., and Y.L. analyzed the PA imaging data. Z.W., L.L., Y.Y., W.G., and L.V.W. interpreted data and wrote the manuscript. All authors reviewed the manuscript. \n\nCompeting interests: L.V.W. has a financial interest in Microphotoacoustics Inc., CalPACT LLC, and Union Photoacoustic Technologies Ltd., which, however, did not support this work. The other authors declare that they have no competing financial interests. \n\nData and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper or the Supplementary Materials.\n\nAccepted Version - nihms-1047257.pdf
Supplemental Material - aax0613_Movie_S1.avi
Supplemental Material - aax0613_Movie_S2.avi
Supplemental Material - aax0613_Movie_S3.avi
Supplemental Material - aax0613_Movie_S4.avi
Supplemental Material - aax0613_Movie_S5.avi
Supplemental Material - aax0613_Movie_S6.avi
Supplemental Material - aax0613_SM.pdf
", "abstract": "Recently, tremendous progress in synthetic micro/nanomotors in diverse environment has been made for potential biomedical applications. However, existing micro/nanomotor platforms are inefficient for deep tissue imaging and motion control in vivo. Here, we present a photoacoustic computed tomography (PACT)\u2013guided investigation of micromotors in intestines in vivo. The micromotors enveloped in microcapsules are stable in the stomach and exhibit efficient propulsion in various biofluids once released. The migration of micromotor capsules toward the targeted regions in intestines has been visualized by PACT in real time in vivo. Near-infrared light irradiation induces disintegration of the capsules to release the cargo-loaded micromotors. The intensive propulsion of the micromotors effectively prolongs the retention in intestines. The integration of the newly developed microrobotic system and PACT enables deep imaging and precise control of the micromotors in vivo and promises practical biomedical applications, such as drug delivery.", "date": "2019-07-24", "date_type": "published", "publication": "Science Robotics", "volume": "4", "number": "32", "publisher": "American Association for the Advancement of Science", "pagerange": "Art. No. eaax0613", "id_number": "CaltechAUTHORS:20190724-151755826", "issn": "2470-9476", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190724-151755826", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Caltech" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH", "grant_number": "CA186567" }, { "agency": "NIH", "grant_number": "NS090579" }, { "agency": "NIH", "grant_number": "NS099717" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" }, { "id": "Kavli-Nanoscience-Institute" } ] }, "doi": "10.1126/scirobotics.aax0613", "pmcid": "PMC7337196", "primary_object": { "basename": "aax0613_Movie_S2.avi", "url": "https://authors.library.caltech.edu/records/0jam3-d5733/files/aax0613_Movie_S2.avi" }, "related_objects": [ { "basename": "aax0613_Movie_S3.avi", "url": "https://authors.library.caltech.edu/records/0jam3-d5733/files/aax0613_Movie_S3.avi" }, { "basename": "aax0613_Movie_S4.avi", "url": "https://authors.library.caltech.edu/records/0jam3-d5733/files/aax0613_Movie_S4.avi" }, { "basename": "aax0613_Movie_S5.avi", "url": "https://authors.library.caltech.edu/records/0jam3-d5733/files/aax0613_Movie_S5.avi" }, { "basename": "aax0613_Movie_S6.avi", "url": "https://authors.library.caltech.edu/records/0jam3-d5733/files/aax0613_Movie_S6.avi" }, { "basename": "aax0613_SM.pdf", "url": "https://authors.library.caltech.edu/records/0jam3-d5733/files/aax0613_SM.pdf" }, { "basename": "nihms-1047257.pdf", "url": "https://authors.library.caltech.edu/records/0jam3-d5733/files/nihms-1047257.pdf" }, { "basename": "aax0613_Movie_S1.avi", "url": "https://authors.library.caltech.edu/records/0jam3-d5733/files/aax0613_Movie_S1.avi" } ], "pub_year": "2019", "author_list": "Wu, Zhiguang; Li, Lei; et el." }, { "id": "https://authors.library.caltech.edu/records/2gxy3-7a647", "eprint_id": 94497, "eprint_status": "archive", "datestamp": "2023-08-22 02:02:04", "lastmod": "2023-10-23 16:11:14", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Einav-Tal", "name": { "family": "Einav", "given": "Tal" }, "orcid": "0000-0003-0777-1193" }, { "id": "Phillips-R", "name": { "family": "Phillips", "given": "Rob" }, "orcid": "0000-0003-3082-2809" } ] }, "title": "How the avidity of polymerase binding to the \u201335/\u201310 promoter sites affects gene expression", "ispublished": "pub", "full_text_status": "public", "keywords": "transcription regulation; avidity; statistical mechanics", "note": "\u00a9 2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). \n\nEdited by Ken A. Dill, Stony Brook University, Stony Brook, NY, and approved May 16, 2019 (received for review April 3, 2019). PNAS first published June 13, 2019. \n\nWe thank Suzy Beeler, Vahe Galstyan, Peng (Brian) He, and Zofii Kaczmarek for helpful discussions. This work was supported by the Rosen Center at the California Institute of Technology and the National Institutes of Health through Grant 1R35 GM118043-01. \n\nAuthor contributions: T.E. designed research; T.E. and R.P. performed research; T.E. analyzed data; and T.E. and R.P. wrote the paper. \n\nThe authors declare no conflict of interest. \n\nThis article is a PNAS Direct Submission. \n\nThis article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1905615116/-/DCSupplemental.\n\nPublished - 13340.full.pdf
Submitted - 1904.01847.pdf
Submitted - 597989.full.pdf
Supplemental Material - pnas.1905615116.sapp.pdf
", "abstract": "Although the key promoter elements necessary to drive transcription in Escherichia coli have long been understood, we still cannot predict the behavior of arbitrary novel promoters, hampering our ability to characterize the myriad sequenced regulatory architectures as well as to design new synthetic circuits. This work builds upon a beautiful recent experiment by Urtecho et al. [G. Urtecho, et al., Biochemistry, 68, 1539\u20131551 (2019)] who measured the gene expression of over 10,000 promoters spanning all possible combinations of a small set of regulatory elements. Using these data, we demonstrate that a central claim in energy matrix models of gene expression\u2014that each promoter element contributes independently and additively to gene expression\u2014contradicts experimental measurements. We propose that a key missing ingredient from such models is the avidity between the \u201335 and \u201310 RNA polymerase binding sites and develop what we call a multivalent model that incorporates this effect and can successfully characterize the full suite of gene expression data. We explore several applications of this framework, namely, how multivalent binding at the \u201335 and \u201310 sites can buffer RNA polymerase (RNAP) kinetics against mutations and how promoters that bind overly tightly to RNA polymerase can inhibit gene expression. The success of our approach suggests that avidity represents a key physical principle governing the interaction of RNA polymerase to its promoter.", "date": "2019-07-02", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "116", "number": "27", "publisher": "National Academy of Sciences", "pagerange": "13340-13345", "id_number": "CaltechAUTHORS:20190405-094702005", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190405-094702005", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH", "grant_number": "1R35 GM118043-01" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1073/pnas.1905615116", "pmcid": "PMC6613100", "primary_object": { "basename": "13340.full.pdf", "url": "https://authors.library.caltech.edu/records/2gxy3-7a647/files/13340.full.pdf" }, "related_objects": [ { "basename": "1904.01847.pdf", "url": "https://authors.library.caltech.edu/records/2gxy3-7a647/files/1904.01847.pdf" }, { "basename": "597989.full.pdf", "url": "https://authors.library.caltech.edu/records/2gxy3-7a647/files/597989.full.pdf" }, { "basename": "pnas.1905615116.sapp.pdf", "url": "https://authors.library.caltech.edu/records/2gxy3-7a647/files/pnas.1905615116.sapp.pdf" } ], "pub_year": "2019", "author_list": "Einav, Tal and Phillips, Rob" }, { "id": "https://authors.library.caltech.edu/records/8xbxe-vsk78", "eprint_id": 96204, "eprint_status": "archive", "datestamp": "2023-08-19 16:23:27", "lastmod": "2023-10-20 20:58:39", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhang-Juner", "name": { "family": "Zhang", "given": "Juner" }, "orcid": "0000-0001-8181-1187" }, { "id": "Huang-Xiongyi", "name": { "family": "Huang", "given": "Xiongyi" }, "orcid": "0000-0001-7156-8881" }, { "id": "Zhang-Ruijie-K", "name": { "family": "Zhang", "given": "Ruijie K." }, "orcid": "0000-0002-7251-5527" }, { "id": "Arnold-F-H", "name": { "family": "Arnold", "given": "Frances H." }, "orcid": "0000-0002-4027-364X" } ] }, "title": "Enantiodivergent \u03b1-Amino C\u2013H Fluoroalkylation Catalyzed by Engineered Cytochrome P450s", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 American Chemical Society. \n\nReceived: April 22, 2019; Published: June 7, 2019. \n\nThis work was supported by the National Science Foundation (NSF), Division of Molecular and Cellular Biosciences (grant MCB-1513007). X.H. is supported by an NIH pathway to independence award (Grant K99GM129419). R.K.Z. acknowledges support from the NSF Graduate Research Fellowship (grant DGE-1144469) and the Donna and Benjamin M. Rosen Bioengineering Center. We thank S. Brinkmann-Chen, K. Chen, Z. Jia, S. B. J. Kan, A. M. Knight, L. J. Schaus, D. J. Wackelin, E. J. Watkins, and Y. Yang for helpful discussion and comments. We also thank N. Torian, M. Shahoholi and the Caltech Mass Spectrometry Laboratory, and L. M. Henling and the Caltech X-ray Crystallography Facility for analytical support. \n\nAuthor Contributions: J.Z. and X.H. contributed equally. \n\nThe authors declare no competing financial interest.\n\nAccepted Version - nihms-1038275.pdf
Supplemental Material - ja9b04344_si_001.pdf
Supplemental Material - ja9b04344_si_002.cif
Supplemental Material - ja9b04344_si_003.cif
", "abstract": "The introduction of fluoroalkyl groups into organic compounds can significantly alter pharmacological characteristics. One enabling but underexplored approach for the installation of fluoroalkyl groups is selective C(sp^3)\u2013H functionalization due to the ubiquity of C\u2013H bonds in organic molecules. We have engineered heme enzymes that can insert fluoroalkyl carbene intermediates into \u03b1-amino C(sp3)\u2013H bonds and enable enantiodivergent synthesis of fluoroalkyl-containing molecules. Using directed evolution, we engineered cytochrome P450 enzymes to catalyze this abiological reaction under mild conditions with total turnovers (TTN) up to 4070 and enantiomeric excess (ee) up to 99%. The iron-heme catalyst is fully genetically encoded and configurable by directed evolution so that just a few mutations to the enzyme completely inverted product enantioselectivity. These catalysts provide a powerful method for synthesis of chiral organofluorine molecules that is currently not possible with small-molecule catalysts.", "date": "2019-06-26", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "141", "number": "25", "publisher": "American Chemical Society", "pagerange": "9798-9802", "id_number": "CaltechAUTHORS:20190607-130827085", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190607-130827085", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "MCB-1513007" }, { "agency": "NIH", "grant_number": "K99GM129419" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1144469" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1021/jacs.9b04344", "pmcid": "PMC6666315", "primary_object": { "basename": "ja9b04344_si_001.pdf", "url": "https://authors.library.caltech.edu/records/8xbxe-vsk78/files/ja9b04344_si_001.pdf" }, "related_objects": [ { "basename": "ja9b04344_si_002.cif", "url": "https://authors.library.caltech.edu/records/8xbxe-vsk78/files/ja9b04344_si_002.cif" }, { "basename": "ja9b04344_si_003.cif", "url": "https://authors.library.caltech.edu/records/8xbxe-vsk78/files/ja9b04344_si_003.cif" }, { "basename": "nihms-1038275.pdf", "url": "https://authors.library.caltech.edu/records/8xbxe-vsk78/files/nihms-1038275.pdf" } ], "pub_year": "2019", "author_list": "Zhang, Juner; Huang, Xiongyi; et el." }, { "id": "https://authors.library.caltech.edu/records/bmacn-7y974", "eprint_id": 90698, "eprint_status": "archive", "datestamp": "2023-08-19 15:31:24", "lastmod": "2023-10-20 21:58:45", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rajendran-Pradeep-S", "name": { "family": "Rajendran", "given": "Pradeep S." }, "orcid": "0000-0001-9790-0408" }, { "id": "Challis-Rosemary-C", "name": { "family": "Challis", "given": "Rosemary C." }, "orcid": "0000-0003-3086-6553" }, { "id": "Fowlkes-Charless-C", "name": { "family": "Fowlkes", "given": "Charless C." }, "orcid": "0000-0002-2990-1780" }, { "id": "Hanna-Peter", "name": { "family": "Hanna", "given": "Peter" } }, { "id": "Tompkins-John-D", "name": { "family": "Tompkins", "given": "John D." } }, { "id": "Jordan-Maria-C", "name": { "family": "Jordan", "given": "Maria C." } }, { "id": "Hiyari-Sarah", "name": { "family": "Hiyari", "given": "Sarah" } }, { "id": "Gabris-Weber-Beth-A", "name": { "family": "Gabris-Weber", "given": "Beth A." } }, { "id": "Greenbaum-Alon", "name": { "family": "Greenbaum", "given": "Alon" }, "orcid": "0000-0002-2897-876X" }, { "id": "Chan-Ken-Y", "name": { "family": "Chan", "given": "Ken Y." }, "orcid": "0000-0002-8853-5186" }, { "id": "Deverman-Benjamin-E", "name": { "family": "Deverman", "given": "Benjamin E." }, "orcid": "0000-0002-6223-9303" }, { "id": "Munzberg-Heike", "name": { "family": "Munzberg", "given": "Heike" } }, { "id": "Ardell-Jeffrey-L", "name": { "family": "Ardell", "given": "Jeffrey L." } }, { "id": "Salama-Guy", "name": { "family": "Salama", "given": "Guy" }, "orcid": "0000-0002-5306-8178" }, { "id": "Gradinaru-V", "name": { "family": "Gradinaru", "given": "Viviana" }, "orcid": "0000-0001-5868-348X" }, { "id": "Shivkumar-Kalyanam", "name": { "family": "Shivkumar", "given": "Kalyanam" }, "orcid": "0000-0002-4121-1766" } ] }, "title": "Identification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. \n\nReceived 09 October 2018; Accepted 27 March 2019; Published 26 April 2019. \n\nData availability: The data that support the findings of this study are available from the corresponding authors upon reasonable request. Viral vectors and protocols are available through Addgene or Beckman Institute for CLARITY, Optogenetics, and Vector Engineering Research for technology development and broad dissemination: http://www.beckmaninstitute.caltech.edu/clover.shtml. \n\nCode availability: Nerve fiber visualization and analysis algorithms used in this study are available are available at: https://www.ics.uci.edu/~fowlkes/SPARC/volume/. \n\nWe thank the entire Shivkumar and Gradinaru group for discussions. This work was supported by a NIH Stimulating Peripheral Activity to Relieve Conditions (SPARC) awards (OT2OD023848 to K.S. and V.G.; OT2OD23864 to H.M.). The K.S. laboratory is also supported by a NIH National Heart, Lung, and Blood Institute (NHLBI) grant (R01HL084261) and a NIH SPARC award (U01EB025138-01 to K.S. and J.L.A.). The V.G. laboratory is also supported by a NIH Director's New Innovator Award (DP2NS087949), a NIH Presidential Early Career Award for Scientists and Engineers, a NIH National Institute on Aging grant (R01AG047664), a NIH BRAIN Initiative award (U01NS090577), the Defense Advanced Research Projects Agency (DARPA) Biological Technologies Office, the National Science Foundation NeuroNex Technology Hub (1707316), the Curci Foundation, the Beckman Institute, and the Rosen Bioengineering Center at Caltech. V.G. is a Heritage Principal Investigator supported by the Heritage Medical Research Institute. P.S.R. was supported by a NIH NHLBI F31 Predoctoral Fellowship (F31HL127974). R.C.C. was supported by an American Heart Association Postdoctoral Fellowship (17POST33410404). P.S.R. is a part of the UCLA-Caltech Medical Scientist Training Program. We thank Drs. Marmar Vaseghi (UCLA), Olujimi A. Ajijola (UCLA), and Ching Zhu (UCLA) for their comments on the manuscript. \n\nAuthor Contributions: P.S.R., R.C.C., J.L.A., V.G., and K.S. designed the study. P.S.R, S.H., and R.C.C. performed heart clearing. A.G. and P.S.R. performed lightsheet imaging of cleared hearts. K.Y.C., B.E.D., R.C.C., and V.G. designed viral constructs. R.C.C. and K.Y.C. produced viruses. R.C.C. and P.S.R. performed retro-orbital injections. C.C.F. developed computational pipeline, performed fiber tracing, and analyzed stellate ganglia CTB data. P.S.R. and R.C.C. performed immunohistochemistry. P.S.R. performed optogenetic experiments. J.D.T. helped with optogenetic experiments. M.C.J. performed cardiac CTB injections. P.S.R., P.H., S.H., B.A.G-.W., and G.S. analyzed data. H.M. provided guidance on TH mouse line selection. P.S.R. and R.C.C. prepared the figures. P.S.R. and K.S. wrote the manuscript. All coauthors contributed to the final version of the manuscript. \n\nThe authors declare no competing interests.\n\nPublished - s41467-019-09770-1.pdf
Submitted - 456483.full.pdf
Supplemental Material - 41467_2019_9770_MOESM10_ESM.mp4
Supplemental Material - 41467_2019_9770_MOESM11_ESM.mp4
Supplemental Material - 41467_2019_9770_MOESM1_ESM.pdf
Supplemental Material - 41467_2019_9770_MOESM2_ESM.pdf
Supplemental Material - 41467_2019_9770_MOESM3_ESM.pdf
Supplemental Material - 41467_2019_9770_MOESM4_ESM.pdf
Supplemental Material - 41467_2019_9770_MOESM5_ESM.mp4
Supplemental Material - 41467_2019_9770_MOESM6_ESM.mp4
Supplemental Material - 41467_2019_9770_MOESM7_ESM.mp4
Supplemental Material - 41467_2019_9770_MOESM8_ESM.mp4
Supplemental Material - 41467_2019_9770_MOESM9_ESM.mp4
", "abstract": "Heart rate is under the precise control of the autonomic nervous system. However, the wiring of peripheral neural circuits that regulate heart rate is poorly understood. Here, we develop a clearing-imaging-analysis pipeline to visualize innervation of intact hearts in 3D and employed a multi-technique approach to map parasympathetic and sympathetic neural circuits that control heart rate in mice. We identify cholinergic neurons and noradrenergic neurons in an intrinsic cardiac ganglion and the stellate ganglia, respectively, that project to the sinoatrial node. We also report that the heart rate response to optogenetic versus electrical stimulation of the vagus nerve displays different temporal characteristics and that vagal afferents enhance parasympathetic and reduce sympathetic tone to the heart via central mechanisms. Our findings provide new insights into neural regulation of heart rate, and our methodology to study cardiac circuits can be readily used to interrogate neural control of other visceral organs.", "date": "2019-04-26", "date_type": "published", "publication": "Nature Communications", "volume": "10", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 1944", "id_number": "CaltechAUTHORS:20181107-092306925", "issn": "2041-1723", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181107-092306925", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "OT2OD023848" }, { "agency": "NIH", "grant_number": "OT2OD23864" }, { "agency": "NIH", "grant_number": "R01HL084261" }, { "agency": "NIH", "grant_number": "U01EB025138-01" }, { "agency": "NIH", "grant_number": "DP2NS087949" }, { "agency": "NIH", "grant_number": "R01AG047664" }, { "agency": "NIH", "grant_number": "U01NS090577" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)" }, { "agency": "NSF", "grant_number": "DBI-1707316" }, { "agency": "Curci Foundation" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Heritage Medical Research Institute" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "F31HL127974" }, { "agency": "American Heart Association", "grant_number": "17POST33410404" }, { "agency": "UCLA-Caltech Medical Scientist Training Program" } ] }, "local_group": { "items": [ { "id": "Heritage-Medical-Research-Institute" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1038/s41467-019-09770-1", "pmcid": "PMC6486614", "primary_object": { "basename": "s41467-019-09770-1.pdf", "url": "https://authors.library.caltech.edu/records/bmacn-7y974/files/s41467-019-09770-1.pdf" }, "related_objects": [ { "basename": "41467_2019_9770_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/bmacn-7y974/files/41467_2019_9770_MOESM1_ESM.pdf" }, { "basename": "41467_2019_9770_MOESM2_ESM.pdf", "url": "https://authors.library.caltech.edu/records/bmacn-7y974/files/41467_2019_9770_MOESM2_ESM.pdf" }, { "basename": "41467_2019_9770_MOESM3_ESM.pdf", "url": "https://authors.library.caltech.edu/records/bmacn-7y974/files/41467_2019_9770_MOESM3_ESM.pdf" }, { "basename": "41467_2019_9770_MOESM4_ESM.pdf", "url": "https://authors.library.caltech.edu/records/bmacn-7y974/files/41467_2019_9770_MOESM4_ESM.pdf" }, { "basename": "41467_2019_9770_MOESM7_ESM.mp4", "url": "https://authors.library.caltech.edu/records/bmacn-7y974/files/41467_2019_9770_MOESM7_ESM.mp4" }, { "basename": "41467_2019_9770_MOESM9_ESM.mp4", "url": "https://authors.library.caltech.edu/records/bmacn-7y974/files/41467_2019_9770_MOESM9_ESM.mp4" }, { "basename": "41467_2019_9770_MOESM8_ESM.mp4", "url": "https://authors.library.caltech.edu/records/bmacn-7y974/files/41467_2019_9770_MOESM8_ESM.mp4" }, { "basename": "41467_2019_9770_MOESM10_ESM.mp4", "url": "https://authors.library.caltech.edu/records/bmacn-7y974/files/41467_2019_9770_MOESM10_ESM.mp4" }, { "basename": "41467_2019_9770_MOESM11_ESM.mp4", "url": "https://authors.library.caltech.edu/records/bmacn-7y974/files/41467_2019_9770_MOESM11_ESM.mp4" }, { "basename": "41467_2019_9770_MOESM5_ESM.mp4", "url": "https://authors.library.caltech.edu/records/bmacn-7y974/files/41467_2019_9770_MOESM5_ESM.mp4" }, { "basename": "456483.full.pdf", "url": "https://authors.library.caltech.edu/records/bmacn-7y974/files/456483.full.pdf" }, { "basename": "41467_2019_9770_MOESM6_ESM.mp4", "url": "https://authors.library.caltech.edu/records/bmacn-7y974/files/41467_2019_9770_MOESM6_ESM.mp4" } ], "pub_year": "2019", "author_list": "Rajendran, Pradeep S.; Challis, Rosemary C.; et el." }, { "id": "https://authors.library.caltech.edu/records/cz0xm-bfr24", "eprint_id": 91986, "eprint_status": "archive", "datestamp": "2023-08-19 15:20:12", "lastmod": "2023-10-20 22:00:47", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Galstyan-Vahe", "name": { "family": "Galstyan", "given": "Vahe" }, "orcid": "0000-0001-7073-9175" }, { "id": "Funk-Luke", "name": { "family": "Funk", "given": "Luke" } }, { "id": "Einav-Tal", "name": { "family": "Einav", "given": "Tal" }, "orcid": "0000-0003-0777-1193" }, { "id": "Phillips-R", "name": { "family": "Phillips", "given": "Rob" }, "orcid": "0000-0003-3082-2809" } ] }, "title": "Combinatorial Control through Allostery", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 American Chemical Society. \n\nReceived: December 28, 2018; Revised: February 5, 2019; Published: February 15, 2019. \n\nIt is a great pleasure to acknowledge the contributions of Bill Eaton to our understanding of allostery. We thank Chandana Gopalakrishnappa and Parijat Sil for their input on this work, and Michael Elowitz for his insights and valuable feedback on the manuscript. This research was supported by La Fondation Pierre-Gilles de Gennes, the Rosen Center at Caltech, the Department of Defense through the National Defense Science & Engineering Graduate Fellowship (NDSEG) Program (LF), and the National Institutes of Health DP1 OD000217 (Director's Pioneer Award), R01 GM085286, and 1R35 GM118043-01 (MIRA). We are grateful to the Burroughs Wellcome Fund for its support of the Physical Biology of the Cell Course at the Marine Biological Laboratory, where part of this work was completed. \n\nAuthor Contributions: V.G. and L.F. contributed equally to this work. \n\nThe authors declare no competing financial interest.\n\nAccepted Version - nihms-1015047.pdf
Submitted - 1812.11290.pdf
Submitted - 508226.full.pdf
Supplemental Material - jp8b12517_si_001.zip
Supplemental Material - jp8b12517_si_002.pdf
Supplemental Material - jp8b12517_si_003.zip
", "abstract": "Many instances of cellular signaling and transcriptional regulation involve switch-like molecular responses to the presence or absence of input ligands. To understand how these responses come about and how they can be harnessed, we develop a statistical mechanical model to characterize the types of Boolean logic that can arise from allosteric molecules following the Monod\u2013Wyman\u2013Changeux (MWC) model. Building upon previous work, we show how an allosteric molecule regulated by two inputs can elicit AND, OR, NAND, and NOR responses but is unable to realize XOR or XNOR gates. Next, we demonstrate the ability of an MWC molecule to perform ratiometric sensing\u2014a response behavior where activity depends monotonically on the ratio of ligand concentrations. We then extend our analysis to more general schemes of combinatorial control involving either additional binding sites for the two ligands or an additional third ligand and show how these additions can cause a switch in the logic behavior of the molecule. Overall, our results demonstrate the wide variety of control schemes that biological systems can implement using simple mechanisms.", "date": "2019-04-04", "date_type": "published", "publication": "Journal of Physical Chemistry B", "volume": "123", "number": "13", "publisher": "American Chemical Society", "pagerange": "2792-2800", "id_number": "CaltechAUTHORS:20190102-135256302", "issn": "1520-6106", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190102-135256302", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "La Fondation Pierre-Gilles de Gennes" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "National Defense Science and Engineering Graduate (NDSEG) Fellowship" }, { "agency": "NIH", "grant_number": "DP1 OD000217" }, { "agency": "NIH", "grant_number": "R01 GM085286" }, { "agency": "NIH", "grant_number": "1R35 GM118043-01" }, { "agency": "Burroughs-Wellcome Fund" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1021/acs.jpcb.8b12517", "pmcid": "PMC6467274", "primary_object": { "basename": "jp8b12517_si_003.zip", "url": "https://authors.library.caltech.edu/records/cz0xm-bfr24/files/jp8b12517_si_003.zip" }, "related_objects": [ { "basename": "nihms-1015047.pdf", "url": "https://authors.library.caltech.edu/records/cz0xm-bfr24/files/nihms-1015047.pdf" }, { "basename": "1812.11290.pdf", "url": "https://authors.library.caltech.edu/records/cz0xm-bfr24/files/1812.11290.pdf" }, { "basename": "508226.full.pdf", "url": "https://authors.library.caltech.edu/records/cz0xm-bfr24/files/508226.full.pdf" }, { "basename": "jp8b12517_si_001.zip", "url": "https://authors.library.caltech.edu/records/cz0xm-bfr24/files/jp8b12517_si_001.zip" }, { "basename": "jp8b12517_si_002.pdf", "url": "https://authors.library.caltech.edu/records/cz0xm-bfr24/files/jp8b12517_si_002.pdf" } ], "pub_year": "2019", "author_list": "Galstyan, Vahe; Funk, Luke; et el." }, { "id": "https://authors.library.caltech.edu/records/2q6yr-aag28", "eprint_id": 93932, "eprint_status": "archive", "datestamp": "2023-08-22 01:19:25", "lastmod": "2023-10-20 17:32:17", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhang-Xuan", "name": { "family": "Zhang", "given": "Xuan" }, "orcid": "0000-0003-1548-8021" }, { "id": "Vyatskikh-Andrey", "name": { "family": "Vyatskikh", "given": "Andrey" }, "orcid": "0000-0002-6917-6931" }, { "id": "Gao-Huajian", "name": { "family": "Gao", "given": "Huajian" }, "orcid": "0000-0002-8656-846X" }, { "id": "Greer-J-R", "name": { "family": "Greer", "given": "Julia R." }, "orcid": "0000-0002-9675-1508" }, { "id": "Li-Xiaoyan", "name": { "family": "Li", "given": "Xiaoyan" }, "orcid": "0000-0002-2953-9267" } ] }, "title": "Lightweight, flaw-tolerant, and ultrastrong nanoarchitected carbon", "ispublished": "pub", "full_text_status": "public", "keywords": "nanolattices; pyrolytic carbon; octet-truss; iso-truss; specific strength", "note": "\u00a9 2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). \n\nContributed by Huajian Gao, February 9, 2019 (sent for review October 8, 2018; reviewed by Yonggang Huang and Christopher M. Spadaccini). PNAS published ahead of print March 18, 2019. \n\nThis work was supported by the Department of Defense through a Vannevar-Bush Faculty Fellowship (to J.R.G.), National Natural Science Foundation of China Grants 11522218 and 11720101002 (to X.L.), National Basic Research of China Grant 2015CB932500 (to X.L.), and National Science Foundation Grant DMR-1709318 (to H.G.).\n\nPublished - 6665.full.pdf
Supplemental Material - pnas.1817309116.sapp.pdf
Supplemental Material - pnas.1817309116.sm01.avi
Supplemental Material - pnas.1817309116.sm02.avi
", "abstract": "It has been a long-standing challenge in modern material design to create low-density, lightweight materials that are simultaneously robust against defects and can withstand extreme thermomechanical environments, as these properties are often mutually exclusive: The lower the density, the weaker and more fragile the material. Here, we develop a process to create nanoarchitected carbon that can attain specific strength (strength-to-density ratio) up to one to three orders of magnitude above that of existing micro- and nanoarchitected materials. We use two-photon lithography followed by pyrolysis in a vacuum at 900 \u00b0C to fabricate pyrolytic carbon in two topologies, octet- and iso-truss, with unit-cell dimensions of \u223c2 \u03bcm, beam diameters between 261 nm and 679 nm, and densities of 0.24 to 1.0 g/cm^3. Experiments and simulations demonstrate that for densities higher than 0.95 g/cm^3 the nanolattices become insensitive to fabrication-induced defects, allowing them to attain nearly theoretical strength of the constituent material. The combination of high specific strength, low density, and extensive deformability before failure lends such nanoarchitected carbon to being a particularly promising candidate for applications under harsh thermomechanical environments.", "date": "2019-04-02", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "116", "number": "14", "publisher": "National Academy of Sciences", "pagerange": "6665-6672", "id_number": "CaltechAUTHORS:20190318-133734983", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190318-133734983", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Vannever Bush Faculty Fellowship" }, { "agency": "National Natural Science Foundation of China", "grant_number": "11522218" }, { "agency": "National Natural Science Foundation of China", "grant_number": "11720101002" }, { "agency": "National Basic Research of China", "grant_number": "2015CB932500" }, { "agency": "NSF", "grant_number": "DMR-1709318" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1073/pnas.1817309116", "pmcid": "PMC6452738", "primary_object": { "basename": "pnas.1817309116.sapp.pdf", "url": "https://authors.library.caltech.edu/records/2q6yr-aag28/files/pnas.1817309116.sapp.pdf" }, "related_objects": [ { "basename": "pnas.1817309116.sm01.avi", "url": "https://authors.library.caltech.edu/records/2q6yr-aag28/files/pnas.1817309116.sm01.avi" }, { "basename": "pnas.1817309116.sm02.avi", "url": "https://authors.library.caltech.edu/records/2q6yr-aag28/files/pnas.1817309116.sm02.avi" }, { "basename": "6665.full.pdf", "url": "https://authors.library.caltech.edu/records/2q6yr-aag28/files/6665.full.pdf" } ], "pub_year": "2019", "author_list": "Zhang, Xuan; Vyatskikh, Andrey; et el." }, { "id": "https://authors.library.caltech.edu/records/hfyt9-r7438", "eprint_id": 98455, "eprint_status": "archive", "datestamp": "2023-08-19 15:16:22", "lastmod": "2023-10-18 17:22:55", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yang-Kevin-K", "name": { "family": "Yang", "given": "Kevin K." }, "orcid": "0000-0001-9045-6826" }, { "id": "Chen-Yuxin", "name": { "family": "Chen", "given": "Yuxin" } }, { "id": "Lee-Alycia-Y", "name": { "family": "Lee", "given": "Alycia" }, "orcid": "0000-0001-5972-807X" }, { "id": "Yue-Yisong", "name": { "family": "Yue", "given": "Yisong" }, "orcid": "0000-0001-9127-1989" } ] }, "title": "Batched Stochastic Bayesian Optimization via Combinatorial Constraints Design", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 by the author(s). \n\nThis work was supported in part by the Donna and Benjamin M. Rosen Bioengineering Center, the U.S. Army Research Office Institute for Collaborative Biotechnologies, NSF Award #1645832, Northrop Grumman, Bloomberg, PIMCO, and a Swiss NSF Early Mobility Postdoctoral Fellowship.\n\nPublished - yang19c.pdf
Submitted - 1904.08102.pdf
Supplemental Material - yang19c-supp.pdf
", "abstract": "In many high-throughput experimental design settings, such as those common in biochemical engineering, batched queries are often more cost effective than one-by-one sequential queries. Furthermore, it is often not possible to directly choose items to query. Instead, the experimenter specifies a set of constraints that generates a library of possible items, which are then selected stochastically. Motivated by these considerations, we investigate \\emph{Batched Stochastic Bayesian Optimization} (BSBO), a novel Bayesian optimization scheme for choosing the constraints in order to guide exploration towards items with greater utility. We focus on \\emph{site-saturation mutagenesis}, a prototypical setting of BSBO in biochemical engineering, and propose a natural objective function for this problem. Importantly, we show that our objective function can be efficiently decomposed as a difference of submodular functions (DS), which allows us to employ DS optimization tools to greedily identify sets of constraints that increase the likelihood of finding items with high utility. Our experimental results show that our algorithm outperforms common heuristics on both synthetic and two real protein datasets.", "date": "2019-04", "date_type": "published", "publication": "Proceedings of Machine Learning Research", "volume": "89", "publisher": "PMLR", "pagerange": "3410-3419", "id_number": "CaltechAUTHORS:20190905-154254753", "issn": "2640-3498", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190905-154254753", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Army Research Office (ARO)" }, { "agency": "NSF", "grant_number": "CNS-1645832" }, { "agency": "Northrop Grumman Corporation" }, { "agency": "Bloomberg Data Science" }, { "agency": "PIMCO" }, { "agency": "Swiss National Science Foundation (SNSF)" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.48550/arXiv.1904.08102", "primary_object": { "basename": "1904.08102.pdf", "url": "https://authors.library.caltech.edu/records/hfyt9-r7438/files/1904.08102.pdf" }, "related_objects": [ { "basename": "yang19c-supp.pdf", "url": "https://authors.library.caltech.edu/records/hfyt9-r7438/files/yang19c-supp.pdf" }, { "basename": "yang19c.pdf", "url": "https://authors.library.caltech.edu/records/hfyt9-r7438/files/yang19c.pdf" } ], "pub_year": "2019", "author_list": "Yang, Kevin K.; Chen, Yuxin; et el." }, { "id": "https://authors.library.caltech.edu/records/8zkw6-7ds08", "eprint_id": 90453, "eprint_status": "archive", "datestamp": "2023-08-19 15:04:34", "lastmod": "2023-10-18 23:27:33", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhang-Ruijie-K", "name": { "family": "Zhang", "given": "Ruijie K." }, "orcid": "0000-0002-7251-5527" }, { "id": "Huang-Xiongyi", "name": { "family": "Huang", "given": "Xiongyi" }, "orcid": "0000-0001-7156-8881" }, { "id": "Arnold-F-H", "name": { "family": "Arnold", "given": "Frances H." }, "orcid": "0000-0002-4027-364X" } ] }, "title": "Selective C-H bond functionalization with engineered heme proteins: new tools to generate complexity", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2018 Elsevier. \n\nAvailable online 18 October 2018. \n\nThis work was supported by the NSF, Division of Molecular and Cellular Biosciences (grant MCB-1513007). R. K. Z. acknowledges support from the NSF Graduate Research Fellowship (grant DGE-1144469) and the Donna and Benjamin M. Rosen Bioengineering Center. X. H. is supported by an NIH pathway to independence award (grant K99GM129419). \n\nConflict of interest statement: Nothing declared.\n\nAccepted Version - nihms-1510154.pdf
", "abstract": "C-H functionalization is an attractive strategy to construct and diversify molecules. Heme proteins, predominantly cytochromes P450, are responsible for an array of C-H oxidations in biology. Recent work has coupled concepts from synthetic chemistry, computation, and natural product biosynthesis to engineer heme protein systems to deliver products with tailored oxidation patterns. Heme protein catalysis has been shown to go well beyond these native reactions and now accesses new-to-nature C-H transformations, including C-N and C-C bond forming processes. Emerging work with these systems moves us along the ambitious path of building complexity from the ubiquitous C-H bond.", "date": "2019-04", "date_type": "published", "publication": "Current Opinion in Chemical Biology", "volume": "49", "publisher": "Elsevier", "pagerange": "67-75", "id_number": "CaltechAUTHORS:20181029-094838266", "issn": "1367-5931", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181029-094838266", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NSF", "grant_number": "MCB-1513007" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1144469" }, { "agency": "NIH", "grant_number": "K99GM129419" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1016/j.cbpa.2018.10.004", "pmcid": "PMC6461521", "primary_object": { "basename": "nihms-1510154.pdf", "url": "https://authors.library.caltech.edu/records/8zkw6-7ds08/files/nihms-1510154.pdf" }, "pub_year": "2019", "author_list": "Zhang, Ruijie K.; Huang, Xiongyi; et el." }, { "id": "https://authors.library.caltech.edu/records/kahnc-n5z12", "eprint_id": 91992, "eprint_status": "archive", "datestamp": "2023-08-22 01:04:31", "lastmod": "2023-10-19 23:53:01", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Cho-Inha", "name": { "family": "Cho", "given": "Inha" }, "orcid": "0000-0002-7564-5378" }, { "id": "Prier-C-K", "name": { "family": "Prier", "given": "Christopher K." }, "orcid": "0000-0003-0902-1636" }, { "id": "Jia-Zhi-Jun", "name": { "family": "Jia", "given": "Zhi-Jun" }, "orcid": "0000-0002-5143-4875" }, { "id": "Zhang-Ruijie-K", "name": { "family": "Zhang", "given": "Ruijie K." }, "orcid": "0000-0002-7251-5527" }, { "id": "G\u00f6rbe-T", "name": { "family": "G\u00f6rbe", "given": "Tam\u00e1s" } }, { "id": "Arnold-F-H", "name": { "family": "Arnold", "given": "Frances H." }, "orcid": "0000-0002-4027-364X" } ] }, "title": "Enantioselective Aminohydroxylation of Styrenyl Olefins Catalyzed by an Engineered Hemoprotein", "ispublished": "pub", "full_text_status": "public", "keywords": "alkenes; amino alcohols; biocatalysis; directed evolution; heme proteins; nitrenes", "note": "\u00a9 2019 WILEY\u2010VCH Verlag. \n\nManuscript received: November 12, 2018; Accepted manuscript online: January 2, 2019; Version of record online: January 25, 2019. \n\nWe thank Kai Chen and Dr. Xiongyi Huang for helpful discussions and assistance with ee determination. We also thank X.\u2005H. and Dr. Sabine Brinkmann\u2010Chen for proofreading the manuscript. We acknowledge the National Science Foundation, Division of Molecular and Cellular Biosciences (grant MCB\u20101513007) for supporting this work. C.K.P. thanks the Resnick Sustainability Institute for a postdoctoral fellowship. R.K.Z. was supported by a National Science Foundation Graduate Research Fellowship (DGE\u20101144469), the Caltech Biotechnology Leadership Program, and the Donna and Benjamin\u2005M. Rosen Bioengineering Center. Z.\u2010J.J. is supported by the Deutsche Forschungsgemeinschaft (JI 289/1\u20101). T.G. thanks for the financial support of the Stiftelsen Olle Engkvist Byggm\u00e4stare and the Kungl. Skogs\u2010och Lantbruksakademien. \n\nThe authors declare no conflict of interest.\n\nSupplemental Material - anie201812968-s1-supporting_information.pdf
", "abstract": "Chiral 1,2\u2010amino alcohols are widely represented in biologically active compounds from neurotransmitters to antivirals. While many synthetic methods have been developed for accessing amino alcohols, the direct aminohydroxylation of alkenes to unprotected, enantioenriched amino alcohols remains a challenge. Using directed evolution, we have engineered a hemoprotein biocatalyst based on a thermostable cytochrome c that directly transforms alkenes to amino alcohols with high enantioselectivity (up to 2500 TTN and 90\u2009% ee) under anaerobic conditions with O\u2010pivaloylhydroxylamine as an aminating reagent. The reaction is proposed to proceed via a reactive iron\u2010nitrogen species generated in the enzyme active site, enabling tuning of the catalyst's activity and selectivity by protein engineering.", "date": "2019-03-04", "date_type": "published", "publication": "Angewandte Chemie International Edition", "volume": "58", "number": "10", "publisher": "Wiley", "pagerange": "3138-3142", "id_number": "CaltechAUTHORS:20190102-135256908", "issn": "1433-7851", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190102-135256908", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "MCB-1513007" }, { "agency": "Resnick Sustainability Institute" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1144469" }, { "agency": "Caltech Biotechnology Leadership Program" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "JI 289/1\u20101" }, { "agency": "Stiftelsen Olle Engkvist Byggm\u00e4stare" }, { "agency": "Kungl. Skogs-och Lantbruksakademien" } ] }, "local_group": { "items": [ { "id": "Resnick-Sustainability-Institute" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1002/anie.201812968", "primary_object": { "basename": "anie201812968-s1-supporting_information.pdf", "url": "https://authors.library.caltech.edu/records/kahnc-n5z12/files/anie201812968-s1-supporting_information.pdf" }, "pub_year": "2019", "author_list": "Cho, Inha; Prier, Christopher K.; et el." }, { "id": "https://authors.library.caltech.edu/records/7yjfx-pw756", "eprint_id": 88862, "eprint_status": "archive", "datestamp": "2023-08-19 14:02:43", "lastmod": "2023-10-20 21:59:12", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Challis-R-C", "name": { "family": "Challis", "given": "Rosemary C." }, "orcid": "0000-0003-3086-6553" }, { "id": "Ravindra-Kumar-S", "name": { "family": "Ravindra Kumar", "given": "Sripriya" }, "orcid": "0000-0001-6033-7631" }, { "id": "Chan-Ken-Y", "name": { "family": "Chan", "given": "Ken Y." }, "orcid": "0000-0002-8853-5186" }, { "id": "Challis-Collin", "name": { "family": "Challis", "given": "Collin" }, "orcid": "0000-0003-4716-6086" }, { "id": "Beadle-K", "name": { "family": "Beadle", "given": "Keith" } }, { "id": "Jang-Min-Jee", "name": { "family": "Jang", "given": "Min J." }, "orcid": "0000-0002-1536-7177" }, { "id": "Kim-Hyun-Min", "name": { "family": "Kim", "given": "Hyun Min" } }, { "id": "Rajendran-P-S", "name": { "family": "Rajendran", "given": "Pradeep S." }, "orcid": "0000-0001-9790-0408" }, { "id": "Tompkins-J-D", "name": { "family": "Tompkins", "given": "John D." } }, { "id": "Shivkumar-K", "name": { "family": "Shivkumar", "given": "Kalyanam" }, "orcid": "0000-0002-4121-1766" }, { "id": "Deverman-B-E", "name": { "family": "Deverman", "given": "Benjamin E." }, "orcid": "0000-0002-6223-9303" }, { "id": "Gradinaru-V", "name": { "family": "Gradinaru", "given": "Viviana" }, "orcid": "0000-0001-5868-348X" } ] }, "title": "Systemic AAV vectors for widespread and targeted gene delivery in rodents", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 Springer Nature Publishing AG. \n\nPublished 09 January 2019. \n\nWe thank M. Fabiszak (W. Freiwald lab, Rockefeller University) and N.C. Flytzanis (V. Gradinaru lab) for the images in Fig. 5d and e, respectively. We also thank M.S. Ladinsky at the Biological and Cryogenic Transmission Electron Microscopy Center (California Institute of Technology (Caltech)) for preparing transmission electron microscopy samples and for acquiring the image shown in Fig. 7b. We are grateful to Y. Lei for help with cloning and K. Lencioni for performing tail-vein injections in rats. The images in Fig. 5a,b were acquired in the Biological Imaging Facility, with the support of the Caltech Beckman Institute and the Arnold and Mabel Beckman Foundation. AAV-PHP capsids are dedicated to the memory of Paul H. Patterson (P.H.P.), who passed away during the preparation of the manuscript describing AAV-PHP.B[3]. This work was primarily supported by the National Institutes of Health (NIH) through grants to V.G.: Director's New Innovator grant DP2NS087949 and PECASE; National Institute on Aging grant R01AG047664; BRAIN grant U01NS090577; SPARC grant OT2OD023848-01 (to V.G. and K.S.); and the Defense Advanced Research Projects Agency (DARPA) Biological Technologies Office (BTO). Additional funding included the NSF NeuroNex Technology Hub grant 1707316, and funds from the Curci Foundation, the Beckman Institute, and the Rosen Center at Caltech. V.G. is a Heritage Principal Investigator supported by the Heritage Medical Research Institute. R.C.C. was supported by an American Heart Association Postdoctoral Fellowship (17POST33410404). C.C. was funded by the National Institute on Aging (F32AG054101), and P.S.R. was funded by the National Heart, Lung, and Blood Institute (F31HL127974). \n\nAuthor Contributions: R.C.C. and V.G. wrote the manuscript with input from all coauthors. S.R.K., K.Y.C., K.B., and B.E.D. optimized the viral production and purification protocols. R.C.C., S.R.K., K.Y.C., C.C., H.K., P.S.R., J.D.T., K.S., B.E.D., and V.G. designed and performed the experiments, analyzed the data, and prepared the figures. M.J.J. analyzed the data in Fig. 2c. V.G. supervised all aspects of the project. All authors edited and approved the manuscript. \n\nCompeting interests: The California Institute of Technology has filed patent applications related to (but not on) this work: Recombinant AAV Capsid Protein (US patent no. 9,585,971); Selective Recovery (US patent application no. 15/422,259); Targeting Peptides for Directing Adeno-Associated Viruses (AAVs) (US patent application no. 15/374,596). The authors declare no other competing interests.\n\nDuring the production process, the authors of this paper supplied revised versions of Figs. 2\u20135, Supplementary Tables 1\u20134, and Supplementary Videos 1\u20133, but because of publisher error, these revised items were not included in the final published version of the protocol. The figures have been updated in the PDF and HTML versions of the paper, and the revised Supplementary Information files are now available online. We note that the figures have been revised to improve their resolution only; the content of the figures and the data reflected remain unchanged. Also, print requirements impose some limits on figure resolution, but the authors have made very high-resolution versions of Figs. 2\u20135 available as Source data.\n\nSubmitted - 246405.full.pdf
Supplemental Material - 41596_2018_97_MOESM1_ESM.pdf
Supplemental Material - 41596_2018_97_MOESM2_ESM.xlsx
Supplemental Material - 41596_2018_97_MOESM3_ESM.xlsx
Supplemental Material - 41596_2018_97_MOESM4_ESM.mp4
Supplemental Material - 41596_2018_97_MOESM5_ESM.mp4
Supplemental Material - 41596_2018_97_MOESM6_ESM.mp4
", "abstract": "We recently developed adeno-associated virus (AAV) capsids to facilitate efficient and noninvasive gene transfer to the central and peripheral nervous systems. However, a detailed protocol for generating and systemically delivering novel AAV variants was not previously available. In this protocol, we describe how to produce and intravenously administer AAVs to adult mice to specifically label and/or genetically manipulate cells in the nervous system and organs, including the heart. The procedure comprises three separate stages: AAV production, intravenous delivery, and evaluation of transgene expression. The protocol spans 8 d, excluding the time required to assess gene expression, and can be readily adopted by researchers with basic molecular biology, cell culture, and animal work experience. We provide guidelines for experimental design and choice of the capsid, cargo, and viral dose appropriate for the experimental aims. The procedures outlined here are adaptable to diverse biomedical applications, from anatomical and functional mapping to gene expression, silencing, and editing.", "date": "2019-02", "date_type": "published", "publication": "Nature Protocols", "volume": "14", "number": "2", "publisher": "Nature Publishing Group", "pagerange": "379-414", "id_number": "CaltechAUTHORS:20180816-125507808", "issn": "1754-2189", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180816-125507808", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Caltech Beckman Institute" }, { "agency": "Arnold and Mabel Beckman Foundation" }, { "agency": "NIH", "grant_number": "DP2NS087949" }, { "agency": "NIH", "grant_number": "R01AG047664" }, { "agency": "NIH", "grant_number": "U01NS090577" }, { "agency": "NIH", "grant_number": "OT2OD023848-01" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)" }, { "agency": "NSF", "grant_number": "DBI-1707316" }, { "agency": "Curci Foundation" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Heritage Medical Research Institute" }, { "agency": "American Heart Association", "grant_number": "17POST33410404" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32AG054101" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F31HL127974" } ] }, "local_group": { "items": [ { "id": "Heritage-Medical-Research-Institute" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1038/s41596-018-0097-3", "primary_object": { "basename": "41596_2018_97_MOESM2_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/7yjfx-pw756/files/41596_2018_97_MOESM2_ESM.xlsx" }, "related_objects": [ { "basename": "41596_2018_97_MOESM3_ESM.xlsx", "url": "https://authors.library.caltech.edu/records/7yjfx-pw756/files/41596_2018_97_MOESM3_ESM.xlsx" }, { "basename": "41596_2018_97_MOESM4_ESM.mp4", "url": "https://authors.library.caltech.edu/records/7yjfx-pw756/files/41596_2018_97_MOESM4_ESM.mp4" }, { "basename": "41596_2018_97_MOESM5_ESM.mp4", "url": "https://authors.library.caltech.edu/records/7yjfx-pw756/files/41596_2018_97_MOESM5_ESM.mp4" }, { "basename": "41596_2018_97_MOESM6_ESM.mp4", "url": "https://authors.library.caltech.edu/records/7yjfx-pw756/files/41596_2018_97_MOESM6_ESM.mp4" }, { "basename": "246405.full.pdf", "url": "https://authors.library.caltech.edu/records/7yjfx-pw756/files/246405.full.pdf" }, { "basename": "41596_2018_97_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/7yjfx-pw756/files/41596_2018_97_MOESM1_ESM.pdf" } ], "pub_year": "2019", "author_list": "Challis, Rosemary C.; Ravindra Kumar, Sripriya; et el." }, { "id": "https://authors.library.caltech.edu/records/cpgg3-3ha18", "eprint_id": 90631, "eprint_status": "archive", "datestamp": "2023-08-19 13:48:04", "lastmod": "2023-10-19 14:41:49", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Abdel-Haq-Reem", "name": { "family": "Abdel-Haq", "given": "Reem" }, "orcid": "0000-0002-7418-5736" }, { "id": "Schlachetzki-Johannes-C-M", "name": { "family": "Schlachetzki", "given": "Johannes C. M." } }, { "id": "Glass-Christopher-K", "name": { "family": "Glass", "given": "Christopher K." }, "orcid": "0000-0003-4344-3592" }, { "id": "Mazmanian-S-K", "name": { "family": "Mazmanian", "given": "Sarkis K." }, "orcid": "0000-0003-2713-1513" } ] }, "title": "Microbiome\u2013microglia connections via the gut\u2013brain axis", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2018 Abdel-Haq et al. This article is distributed under the terms of an Attribution\u2013Noncommercial\u2013Share Alike\u2013No Mirror Sites license for the first six months after the publication date (see http:// www .rupress .org/ terms/ ). After six months it is available under a Creative Commons License (Attribution\u2013Noncommercial\u2013Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). \n\nSubmitted: 29 April 2018; Revision received 8 July 2018; Accepted: 3 October 2018; Published Online: 1 November, 2018. \n\nWe would like to thank members of the Mazmanian and Glass laboratory for their critical review of this manuscript and thoughtful insight and discussion. \n\nR. Abdel-Haq is supported by the U.S. Department of Defense and the Donna and Benjamin M. Rosen Bioengineering Center. Related work in the Glass laboratory is funded by the National Institutes of Health (grants AG057706 and NS096170). Related work in the Mazmanian laboratory is funded by the Heritage Medical Research Institute, the Simons Foundation (grant 322839), the U.S. Department of Defense (PD160030), and the National Institutes of Health (grants MH100556 and NS085910) to S.K. Mazmanian. \n\nThe authors declare no competing financial interests. \n\nAuthor contributions: R. Abdel-Haq wrote the manuscript with support from J.C.M. Schlachetzki. J.C.M. Schlachetzki and C.K. Glass critically reviewed and edited the manuscript. S.K. Mazmanian contributed to the conception and design of the manuscript. All authors reviewed the manuscript before submission.\n\nPublished - 41.full.pdf
", "abstract": "Microglia, the resident immune cells in the brain, are essential for modulating neurogenesis, influencing synaptic remodeling, and regulating neuroinflammation by surveying the brain microenvironment. Microglial dysfunction has been implicated in the onset and progression of several neurodevelopmental and neurodegenerative diseases; however, the multitude of factors and signals influencing microglial activity have not been fully elucidated. Microglia not only respond to local signals within the brain but also receive input from the periphery, including the gastrointestinal (GI) tract. Recent preclinical findings suggest that the gut microbiome plays a pivotal role in regulating microglial maturation and function, and altered microbial community composition has been reported in neurological disorders with known microglial involvement in humans. Collectively, these findings suggest that bidirectional crosstalk between the gut and the brain may influence disease pathogenesis. Herein, we discuss recent studies showing a role for the gut microbiome in modulating microglial development and function in homeostatic and disease conditions and highlight possible future research to develop novel microbial treatments for disorders of the brain.", "date": "2019-01-07", "date_type": "published", "publication": "Journal of Experimental Medicine", "volume": "216", "number": "1", "publisher": "Rockefeller University Press", "pagerange": "41-59", "id_number": "CaltechAUTHORS:20181105-090651605", "issn": "0022-1007", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181105-090651605", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Department of Defense", "grant_number": "PD160030" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH", "grant_number": "AG057706" }, { "agency": "NIH", "grant_number": "NS096170" }, { "agency": "Heritage Medical Research Institute" }, { "agency": "Simons Foundation", "grant_number": "322839" }, { "agency": "NIH", "grant_number": "MH100556" }, { "agency": "NIH", "grant_number": "NS085910" } ] }, "local_group": { "items": [ { "id": "Heritage-Medical-Research-Institute" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1084/jem.20180794", "pmcid": "PMC6314531", "primary_object": { "basename": "41.full.pdf", "url": "https://authors.library.caltech.edu/records/cpgg3-3ha18/files/41.full.pdf" }, "pub_year": "2019", "author_list": "Abdel-Haq, Reem; Schlachetzki, Johannes C. M.; et el." }, { "id": "https://authors.library.caltech.edu/records/3ydkt-yyf88", "eprint_id": 90410, "eprint_status": "archive", "datestamp": "2023-08-19 13:46:51", "lastmod": "2023-10-18 23:25:54", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhang-Ruijie-K", "name": { "family": "Zhang", "given": "Ruijie K." }, "orcid": "0000-0002-7251-5527" }, { "id": "Chen-Kai", "name": { "family": "Chen", "given": "Kai" }, "orcid": "0000-0002-3325-3536" }, { "id": "Huang-Xiongyi", "name": { "family": "Huang", "given": "Xiongyi" }, "orcid": "0000-0001-7156-8881" }, { "id": "Wohlschlager-Lena", "name": { "family": "Wohlschlager", "given": "Lena" } }, { "id": "Renata-Hans", "name": { "family": "Renata", "given": "Hans" }, "orcid": "0000-0003-2468-2328" }, { "id": "Arnold-F-H", "name": { "family": "Arnold", "given": "Frances H." }, "orcid": "0000-0002-4027-364X" } ] }, "title": "Enzymatic assembly of carbon\u2013carbon bonds via iron-catalysed sp\u00b3 C\u2013H functionalization", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2019 Springer Nature Limited. \n\nReceived 18 July 2018; Accepted 01 November 2018; Published\n19 December 2018. \n\nThis work was supported by the National Science Foundation (NSF), Division of Molecular and Cellular Biosciences (grant MCB-1513007). R.K.Z. acknowledges support from the NSF Graduate Research Fellowship (grant DGE-1144469) and the Donna and Benjamin M. Rosen Bioengineering Center. X.H. is supported by a Ruth L. Kirschstein National Institutes of Health Postdoctoral Fellowship (grant F32GM125231). L.W. received support from the Austrian Marshall Plan Foundation. We thank A. Z. Zhou for experimental assistance; N. W. Goldberg, S. C. Hammer, K. E. Hernandez, Z. Jia, A. M. Knight, G. Kubik, R. D. Lewis, C. K. Prier, D. K. Romney and J. Zhang for discussions; S. Virgil, M. Shahgholi and D. VanderVelde for analytical support; and B. Stoltz for use of polarimeter and gas chromatography equipment. \n\nData availability: All relevant data are provided in Supplementary Information. Any additional information is available from the corresponding author on request. \n\nAuthor Contributions: R.K.Z. designed the overall research with F.H.A. providing guidance. R.K.Z. and H.R. designed and conducted the initial screening of haem proteins; R.K.Z. and L.W. performed the directed evolution experiments. R.K.Z., K.C. and X.H. designed and performed the substrate scope studies. R.K.Z. and F.H.A. wrote the manuscript with input from all authors. \n\nCompeting interests: A provisional patent application has been filed through the California Institute of Technology based on the results presented here.\n\nAccepted Version - nihms-1511383.pdf
Supplemental Material - 41586_2018_808_MOESM1_ESM.pdf
", "abstract": "Although abundant in organic molecules, carbon\u2013hydrogen (C\u2013H) bonds are typically considered unreactive and unavailable for chemical manipulation. Recent advances in C\u2013H functionalization technology have begun to transform this logic, while emphasizing the importance of and challenges associated with selective alkylation at a sp\u00b3 carbon. Here we describe iron-based catalysts for the enantio-, regio- and chemoselective intermolecular alkylation of sp\u00b3 C\u2013H bonds through carbene C\u2013H insertion. The catalysts, derived from a cytochrome P450 enzyme in which the native cysteine axial ligand has been substituted for serine (cytochrome P411), are fully genetically encoded and produced in bacteria, where they can be tuned by directed evolution for activity and selectivity. That these proteins activate iron, the most abundant transition metal, to perform this chemistry provides a desirable alternative to noble-metal catalysts, which have dominated the field of C\u2013H functionalization. The laboratory-evolved enzymes functionalize diverse substrates containing benzylic, allylic or \u03b1-amino C\u2013H bonds with high turnover and excellent selectivity. Furthermore, they have enabled the development of concise routes to several natural products. The use of the native iron-haem cofactor of these enzymes to mediate sp\u00b3 C\u2013H alkylation suggests that diverse haem proteins could serve as potential catalysts for this abiological transformation, and will facilitate the development of new enzymatic C\u2013H functionalization reactions for applications in chemistry and synthetic biology.", "date": "2019-01-03", "date_type": "published", "publication": "Nature", "volume": "565", "number": "7737", "publisher": "Nature Publishing Group", "pagerange": "67-72", "id_number": "CaltechAUTHORS:20181025-100754288", "issn": "0028-0836", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181025-100754288", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "MCB-1513007" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1144469" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32GM125231" }, { "agency": "Austrian Marshall Plan Foundation" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1038/s41586-018-0808-5", "pmcid": "PMC6440214", "primary_object": { "basename": "41586_2018_808_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/3ydkt-yyf88/files/41586_2018_808_MOESM1_ESM.pdf" }, "related_objects": [ { "basename": "nihms-1511383.pdf", "url": "https://authors.library.caltech.edu/records/3ydkt-yyf88/files/nihms-1511383.pdf" } ], "pub_year": "2019", "author_list": "Zhang, Ruijie K.; Chen, Kai; et el." }, { "id": "https://authors.library.caltech.edu/records/cve86-hd485", "eprint_id": 90487, "eprint_status": "archive", "datestamp": "2023-08-19 13:25:27", "lastmod": "2023-10-20 22:07:51", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Hochrein-Lisa-M", "name": { "family": "Hochrein", "given": "Lisa M." } }, { "id": "Ge-Tianjia-J", "name": { "family": "Ge", "given": "Tianjia J." } }, { "id": "Schwarzkopf-Maayan", "name": { "family": "Schwarzkopf", "given": "Maayan" }, "orcid": "0000-0001-8128-1059" }, { "id": "Pierce-N-A", "name": { "family": "Pierce", "given": "Niles A." }, "orcid": "0000-0003-2367-4406" } ] }, "title": "Signal Transduction in Human Cell Lysate via Dynamic RNA Nanotechnology", "ispublished": "pub", "full_text_status": "public", "keywords": "small conditional RNA (scRNA), conditional siRNA production, conditional RNAi, molecular programming, dynamic RNA nanotechnology, human cell lysate, RNA degradation, Dicer processing", "note": "\u00a9 2018 American Chemical Society. \n\nReceived: October 9, 2018. Publication Date (Web): December 7, 2018. \n\nWe thank K. Sakurai and J.J. Rossi for advice on preparation of human cell lysate with functional Dicer, B.R. Wolfe and N.J. Porubsky for assistance with reaction pathway engineering using NUPACK, and P.D. Carlson and J.B. Lucks for discussions on profiling mRNA accessibility. This work was funded by the National Institutes of Health (5R01CA140759), by the National Science Foundation Molecular Programming Project (NSF-CCF-1317694), by the Gordon and Betty Moore Foundation (GBMF2809), by the Rosen Bioengineering Center at Caltech, by a Professorial Fellowship at Balliol College (University of Oxford), and by the Eastman Visiting Professorship at the University of Oxford. \n\nThe authors declare the following competing financial interest(s): Patents.\n\nAccepted Version - sb8b00424.pdf
Submitted - 439273.full.pdf
Supplemental Material - sb8b00424_si_001.pdf
", "abstract": "Dynamic RNA nanotechnology with small conditional RNAs (scRNAs) offers a promising conceptual approach to introducing synthetic regulatory links into endogenous biological circuits. Here, we use human cell lysate containing functional Dicer and RNases as a testbed for engineering scRNAs for conditional RNA interference (RNAi). scRNAs perform signal transduction via conditional shape change: detection of a subsequence of mRNA input X triggers formation of a Dicer substrate that is processed to yield small interfering RNA (siRNA) output anti-Y targeting independent mRNA Y for destruction. Automated sequence design is performed using the reaction pathway designer within NUPACK to encode this conditional hybridization cascade into the scRNA sequence subject to the sequence constraints imposed by X and Y. Because it is difficult for secondary structure models to predict which subsequences of mRNA input X will be accessible for detection, here we develop the RNAhyb method to experimentally determine accessible windows within the mRNA that are provided to the designer as sequence constraints. We demonstrate the programmability of scRNA regulators by engineering scRNAs for transducing in both directions between two full-length mRNAs X and Y, corresponding to either the forward molecular logic \"if X then not Y\" (X - Y) or the reverse molecular logic \"if Y then not X\" (Y - X). In human cell lysate, we observe a strong OFF/ON conditional response with low crosstalk, corresponding to a \u224820-fold increase in production of the siRNA output in response to the cognate versus noncognate full-length mRNA input. 2\u2032OMe-RNA chemical modifications protect signal transduction reactants and intermediates against RNase degradation while enabling Dicer processing of signal transduction products. Because diverse biological pathways interact with RNA, scRNAs that transduce between detection of endogenous RNA inputs and production of biologically active RNA outputs hold great promise as a synthetic regulatory paradigm.", "date": "2018-12-21", "date_type": "published", "publication": "ACS Synthetic Biology", "volume": "7", "number": "12", "publisher": "American Chemical Society", "pagerange": "2796-2802", "id_number": "CaltechAUTHORS:20181030-075958683", "issn": "2161-5063", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181030-075958683", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "5R01CA140759" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "Gordon and Betty Moore Foundation", "grant_number": "GBMF2809" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "University of Oxford" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1021/acssynbio.8b00424", "pmcid": "PMC6305621", "primary_object": { "basename": "439273.full.pdf", "url": "https://authors.library.caltech.edu/records/cve86-hd485/files/439273.full.pdf" }, "related_objects": [ { "basename": "sb8b00424.pdf", "url": "https://authors.library.caltech.edu/records/cve86-hd485/files/sb8b00424.pdf" }, { "basename": "sb8b00424_si_001.pdf", "url": "https://authors.library.caltech.edu/records/cve86-hd485/files/sb8b00424_si_001.pdf" } ], "pub_year": "2018", "author_list": "Hochrein, Lisa M.; Ge, Tianjia J.; et el." }, { "id": "https://authors.library.caltech.edu/records/pm3gc-jx894", "eprint_id": 90073, "eprint_status": "archive", "datestamp": "2023-09-22 22:50:07", "lastmod": "2023-10-23 23:29:44", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Rapp-Peter-B", "name": { "family": "Rapp", "given": "Peter B." }, "orcid": "0000-0002-9586-2126" }, { "id": "Omar-Ahmad-K", "name": { "family": "Omar", "given": "Ahmad K." }, "orcid": "0000-0002-6404-7612" }, { "id": "Silverman-Bradley-R", "name": { "family": "Silverman", "given": "Bradley R." }, "orcid": "0000-0002-9256-8941" }, { "id": "Wang-Zhen-Gang", "name": { "family": "Wang", "given": "Zhen-Gang" }, "orcid": "0000-0002-3361-6114" }, { "id": "Tirrell-D-A", "name": { "family": "Tirrell", "given": "David A." }, "orcid": "0000-0003-3175-4596" } ] }, "title": "Mechanisms of diffusion in associative polymer networks: evidence for chain hopping", "ispublished": "pub", "full_text_status": "public", "keywords": "diffusion, mechanism, hopping, entropy, binding, hydrogel, FRAP", "note": "\u00a9 2018 American Chemical Society. \n\nReceived: July 25, 2018; Published: October 1, 2018.\n\nWe thank Andres Collazo of the Caltech Beckman Imaging Facility for expert assistance with acquisition of FRAP data. This work was supported by grant number DMR-1506483 from the Biomaterials Program of the U.S. National Science Foundation. A.K.O. acknowledges support from the National Science Foundation Graduate Research Fellowship under grant no. DGE-1144469 and an HHMI Gilliam Fellowship. B.R.S. acknowledges support from NIH predoctoral training grant 1T32GM112592 and from the Rosen Center for Bioengineering.\n\nP.B.R. and A.K.O. contributed equally to this work.\n\nThe authors declare no competing financial interest.\n\nAccepted Version - nihms-1792560.pdf
Supplemental Material - ja8b07908_si_001.pdf
", "abstract": "Networks assembled by reversible association of telechelic polymers constitute a common class of soft materials. Various mechanisms of chain migration in associative networks have been proposed; yet there remains little quantitative experimental data to discriminate among them. Proposed mechanisms for chain migration include multichain aggregate diffusion as well as single-chain mechanisms such as \"walking\" and \"hopping\", wherein diffusion is achieved by either partial (\"walking\") or complete (\"hopping\") disengagement of the associated chain segments. Here, we provide evidence that hopping can dominate the effective diffusion of chains in associative networks due to a strong entropic penalty for bridge formation imposed by local network structure; chains become conformationally restricted upon association with two or more spatially separated binding sites. This restriction decreases the effective binding strength of chains with multiple associative domains, thereby increasing the probability that a chain will hop. For telechelic chains this manifests as binding asymmetry, wherein the first association is effectively stronger than the second. We derive a simple thermodynamic model that predicts the fraction of chains that are free to hop as a function of tunable molecular and network properties. A large set of self-diffusivity measurements on a series of model associative polymers finds good agreement with this model.", "date": "2018-10-31", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "140", "number": "43", "publisher": "American Chemical Society", "pagerange": "14185-14194", "id_number": "CaltechAUTHORS:20181001-131358075", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181001-131358075", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "DMR-1506483" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1144469" }, { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "1T32GM112592" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1021/jacs.8b07908", "pmcid": "PMC8997312", "primary_object": { "basename": "ja8b07908_si_001.pdf", "url": "https://authors.library.caltech.edu/records/pm3gc-jx894/files/ja8b07908_si_001.pdf" }, "related_objects": [ { "basename": "nihms-1792560.pdf", "url": "https://authors.library.caltech.edu/records/pm3gc-jx894/files/nihms-1792560.pdf" } ], "pub_year": "2018", "author_list": "Rapp, Peter B.; Omar, Ahmad K.; et el." }, { "id": "https://authors.library.caltech.edu/records/8apf9-6sm71", "eprint_id": 90190, "eprint_status": "archive", "datestamp": "2023-08-19 11:35:39", "lastmod": "2023-10-23 15:41:58", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Einav-T", "name": { "family": "Einav", "given": "Tal" }, "orcid": "0000-0003-0777-1193" }, { "id": "Duque-J", "name": { "family": "Duque", "given": "Julia" } }, { "id": "Phillips-R", "name": { "family": "Phillips", "given": "Rob" }, "orcid": "0000-0003-3082-2809" } ] }, "title": "Theoretical analysis of inducer and operator binding for cyclic-AMP receptor protein mutants", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2018 Einav et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. \n\nReceived: July 5, 2018; Accepted: September 5, 2018; Published: September 26, 2018. \n\nData Availability Statement: All relevant data are within the paper and its Supporting Information files. \n\nThis work was supported in the RP group by La Fondation Pierre-Gilles de Gennes, the Rosen Center at Caltech (http://rosen.caltech.edu/), and the National Institutes of Health (https://www.nih.gov/) through DP1 OD000217 (Director's Pioneer Award), R01 GM085286, and 1R35 GM118043-01 (MIRA). We are grateful to the Burroughs-Wellcome Fund (https://www.bwfund.org/) for its support of the Physiology Course at the Marine Biological Laboratory, where part of the work on this work was done, and for a post-course research grant (JD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. \n\nThe authors have declared that no competing interests exist. \n\nWe thank Lacramioara Bintu for bringing the recent developments on CRP to our attention as well as Terry Hwa, Tom Kuhlman, and Michael Manhart for helpful discussions. All plots were made entirely in Mathematica using the CustomTicks package [54] with data obtained from the authors or using WebPlotDigitizer [55]. This work was supported in the RP group by La Fondation Pierre-Gilles de Gennes, the Rosen Center at Caltech, and the National Institutes of Health through DP1 OD000217 (Director's Pioneer Award), R01 GM085286, and 1R35 GM118043-01 (MIRA). We are grateful to the Burroughs-Wellcome Fund for its support of the Physiology Course at the Marine Biological Laboratory, where part of the work on this work was done, and for a post-course research grant (JD). \n\nAuthor Contributions: \nConceptualization: Tal Einav, Julia Duque, Rob Phillips.\nFormal analysis: Tal Einav, Julia Duque, Rob Phillips.\nWriting \u00b1 original draft: Tal Einav, Rob Phillips.\n\nPublished - journal.pone.0204275.pdf
Submitted - 236455.full.pdf
Supplemental Material - journal.pone.0204275.s001.pdf
Supplemental Material - journal.pone.0204275.s002.pdf
", "abstract": "Allosteric transcription factors undergo binding events at inducer binding sites as well as at distinct DNA binding domains, and it is difficult to disentangle the structural and functional consequences of these two classes of interactions. We compare the ability of two statistical mechanical models\u2014the Monod-Wyman-Changeux (MWC) and the Koshland-N\u00e9methy-Filmer (KNF) models of protein conformational change\u2014to characterize the multi-step activation mechanism of the broadly acting cyclic-AMP receptor protein (CRP). We first consider the allosteric transition resulting from cyclic-AMP binding to CRP, then analyze how CRP binds to its operator, and finally investigate the ability of CRP to activate gene expression. We use these models to examine a beautiful recent experiment that created a single-chain version of the CRP homodimer, creating six mutants using all possible combinations of the wild type, D53H, and S62F subunits. We demonstrate that the MWC model can explain the behavior of all six mutants using a small, self-consistent set of parameters whose complexity scales with the number of subunits, providing a significant benefit over previous models. In comparison, the KNF model not only leads to a poorer characterization of the available data but also fails to generate parameter values in line with the available structural knowledge of CRP. In addition, we discuss how the conceptual framework developed here for CRP enables us to not merely analyze data retrospectively, but has the predictive power to determine how combinations of mutations will interact, how double mutants will behave, and how each construct would regulate gene expression.", "date": "2018-09-26", "date_type": "published", "publication": "PLoS ONE", "volume": "13", "number": "9", "publisher": "Public Library of Science", "pagerange": "Art. No. e0204275", "id_number": "CaltechAUTHORS:20181009-105623284", "issn": "1932-6203", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20181009-105623284", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "La Fondation Pierre-Gilles de Gennes" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH", "grant_number": "DP1 OD000217" }, { "agency": "NIH", "grant_number": "R01 GM085286" }, { "agency": "NIH", "grant_number": "1R35 GM118043-01" }, { "agency": "Burroughs-Wellcome Fund" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1371/journal.pone.0204275", "pmcid": "PMC6157895", "primary_object": { "basename": "journal.pone.0204275.pdf", "url": "https://authors.library.caltech.edu/records/8apf9-6sm71/files/journal.pone.0204275.pdf" }, "related_objects": [ { "basename": "journal.pone.0204275.s001.pdf", "url": "https://authors.library.caltech.edu/records/8apf9-6sm71/files/journal.pone.0204275.s001.pdf" }, { "basename": "journal.pone.0204275.s002.pdf", "url": "https://authors.library.caltech.edu/records/8apf9-6sm71/files/journal.pone.0204275.s002.pdf" }, { "basename": "236455.full.pdf", "url": "https://authors.library.caltech.edu/records/8apf9-6sm71/files/236455.full.pdf" } ], "pub_year": "2018", "author_list": "Einav, Tal; Duque, Julia; et el." }, { "id": "https://authors.library.caltech.edu/records/6t6nv-52n04", "eprint_id": 85532, "eprint_status": "archive", "datestamp": "2023-08-19 10:55:00", "lastmod": "2023-10-23 15:44:16", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Yang-Kevin-K", "name": { "family": "Yang", "given": "Kevin K." }, "orcid": "0000-0001-9045-6826" }, { "id": "Wu-Zachary", "name": { "family": "Wu", "given": "Zachary" } }, { "id": "Bedbrook-C-N", "name": { "family": "Bedbrook", "given": "Claire N." }, "orcid": "0000-0003-3973-598X" }, { "id": "Arnold-F-H", "name": { "family": "Arnold", "given": "Frances H." }, "orcid": "0000-0002-4027-364X" } ] }, "title": "Learned Protein Embeddings for Machine Learning", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2018 The Author. Published by Oxford University Press.\nThis article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices). \n\nAvailability and Implementation: The embedding vectors and code to reproduce the results are available\nat https://github.com/fhalab/embeddings_reproduction/. \n\nThe authors wish to thank members of the Arnold lab, Justin Bois, and Yisong Yue for general advice and discussions on this project. \n\nThis work is supported by the U.S. Army Research Office Institute for Collaborative Biotechnologies [W911F-09-0001 to F.H.A., K.K.Y.], the Donna and Benjamin M. Rosen Bioengineering Center [to K.K.Y.], the National Institutes of Health [F31MH102913, to C.N.B], and the National Science Foundation [GRF2017227007 to Z.W.]. \n\nConflict of Interest: none declared.\n\nThe authors of the above paper wish to inform readers that the following article was incorrectly included as a reference: McIsaac, R.S. et al. (2014) Directed evolution of a far-red fluorescent rhodopsin. Proc. Natl. Acad. Sci. USA, 111, 13034\u201313039.\nThe article which should have appeared in its place is: Engqvist, M.K.M. et al. (2015) Directed evolution of Gloeobacter violaceus rhodopsin spectral properties. Journal of Molecular Biology 427, 205-220.\n\nSupplemental Material - bty178_supp.zip
", "abstract": "Motivation: Machine-learning models trained on protein sequences and their measured functions can infer biological properties of unseen sequences without requiring an understanding of the underlying physical or biological mechanisms. Such models enable the prediction and discovery of sequences with optimal properties. Machine-learning models generally require that their inputs be vectors, and the conversion from a protein sequence to a vector representation affects the model's ability to learn. We propose to learn embedded representations of protein sequences that take advantage of the vast quantity of unmeasured protein sequence data available. These embeddings are low-dimensional and can greatly simplify downstream modeling. \n\nResults: The predictive power of Gaussian process models trained using embeddings is comparable to those trained on existing representations, which suggests that embeddings enable accurate predictions despite having orders of magnitude fewer dimensions. Moreover, embeddings are simpler to obtain because they do not require alignments, structural data, or selection of informative amino-acid properties. Visualizing the embedding vectors shows meaningful relationships between the embedded proteins are captured.", "date": "2018-08-01", "date_type": "published", "publication": "Bioinformatics", "volume": "34", "number": "15", "publisher": "Oxford University Press", "pagerange": "2642-2648", "id_number": "CaltechAUTHORS:20180330-110704718", "issn": "1367-4803", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180330-110704718", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Army Research Office (ARO)", "grant_number": "W911F-09-0001" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "F31MH102913" }, { "agency": "NSF", "grant_number": "GRF-2017227007" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1093/bioinformatics/bty178", "pmcid": "PMC6061698", "primary_object": { "basename": "bty178_supp.zip", "url": "https://authors.library.caltech.edu/records/6t6nv-52n04/files/bty178_supp.zip" }, "pub_year": "2018", "author_list": "Yang, Kevin K.; Wu, Zachary; et el." }, { "id": "https://authors.library.caltech.edu/records/8n2xy-avm68", "eprint_id": 85547, "eprint_status": "archive", "datestamp": "2023-08-19 09:25:03", "lastmod": "2023-10-18 18:19:05", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Maresca-David", "name": { "family": "Maresca", "given": "David" }, "orcid": "0000-0002-4921-6406" }, { "id": "Lakshmanan-Anupama", "name": { "family": "Lakshmanan", "given": "Anupama" }, "orcid": "0000-0002-6702-837X" }, { "id": "Abedi-Mohamad-H", "name": { "family": "Abedi", "given": "Mohamad H." }, "orcid": "0000-0001-9717-6288" }, { "id": "Bar-Zion-Avinoam", "name": { "family": "Bar-Zion", "given": "Avinoam" }, "orcid": "0000-0002-7564-9467" }, { "id": "Farhadi-Arash", "name": { "family": "Farhadi", "given": "Arash" }, "orcid": "0000-0001-9137-8559" }, { "id": "Lu-George-Jiaozhi", "name": { "family": "Lu", "given": "George J." }, "orcid": "0000-0002-4689-9686" }, { "id": "Szablowski-Jerzy-O", "name": { "family": "Szablowski", "given": "Jerzy O." }, "orcid": "0000-0001-7851-5408" }, { "id": "Wu-Di", "name": { "family": "Wu", "given": "Di" }, "orcid": "0000-0002-6848-668X" }, { "id": "Yoo-Sangjin", "name": { "family": "Yoo", "given": "Sangjin" }, "orcid": "0000-0002-0449-4242" }, { "id": "Shapiro-M-G", "name": { "family": "Shapiro", "given": "Mikhail G." }, "orcid": "0000-0002-0291-4215" } ] }, "title": "Biomolecular Ultrasound and Sonogenetics", "ispublished": "pub", "full_text_status": "public", "keywords": "biomolecular, ultrasound, sonogenetics, gas vesicles, imaging, reporter gene", "note": "\u00a9 2018 Annual Reviews. \n\nReview in Advance first posted online on March 26, 2018. \n\nThe authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this review. \n\nThe authors thank members of the Shapiro laboratory and collaborators for helpful discussions. Related work in the Shapiro laboratory is supported by the Heritage Medical Research Institute, the National Institutes of Health, the Defense Advanced Research Projects Agency, the Jacobs Institute for Molecular Engineering in Medicine, the Caltech Center for Environmental Microbial Interactions, the Human Frontiers Science Program, the Burroughs Wellcome Fund, the Pew Scholarship in the Biomedical Sciences, the Sontag Foundation, and the Packard Fellowship for Science and Engineering. D.M. is supported by a postdoctoral fellowship from the Human Frontier Science Program. A.L. and M.A. are supported by the National Science Foundation graduate research fellowship.\n\nAccepted Version - nihms979454.pdf
", "abstract": "Visualizing and modulating molecular and cellular processes occurring deep within living organisms is fundamental to our study of basic biology and disease. Currently, the most sophisticated tools available to dynamically monitor and control cellular events rely on light-responsive proteins, which are difficult to use outside of optically transparent model systems, cultured cells, or surgically accessed regions owing to strong scattering of light by biological tissue. In contrast, ultrasound is a widely used medical imaging and therapeutic modality that enables the observation and perturbation of internal anatomy and physiology but has historically had limited ability to monitor and control specific cellular processes. Recent advances are beginning to address this limitation through the development of biomolecular tools that allow ultrasound to connect directly to cellular functions such as gene expression. Driven by the discovery and engineering of new contrast agents, reporter genes, and bioswitches, the nascent field of biomolecular ultrasound carries a wave of exciting opportunities.", "date": "2018-06", "date_type": "published", "publication": "Annual Review of Chemical and Biomolecular Engineering", "volume": "9", "publisher": "Annual Reviews", "pagerange": "229-252", "id_number": "CaltechAUTHORS:20180330-152125173", "issn": "1947-5438", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180330-152125173", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Heritage Medical Research Institute" }, { "agency": "NIH" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)" }, { "agency": "Jacobs Institute for Molecular Engineering for Medicine" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" }, { "agency": "Human Frontier Science Program" }, { "agency": "Burroughs Wellcome Fund" }, { "agency": "Pew Charitable Trust" }, { "agency": "Sontag Foundation" }, { "agency": "David and Lucile Packard Foundation" }, { "agency": "NSF Graduate Research Fellowship" } ] }, "local_group": { "items": [ { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Heritage-Medical-Research-Institute" }, { "id": "Rosen-Bioengineering-Center" }, { "id": "Jacobs-Institute-for-Molecular-Engineering-for-Medicine" } ] }, "doi": "10.1146/annurev-chembioeng-060817-084034", "pmcid": "PMC6086606", "primary_object": { "basename": "nihms979454.pdf", "url": "https://authors.library.caltech.edu/records/8n2xy-avm68/files/nihms979454.pdf" }, "pub_year": "2018", "author_list": "Maresca, David; Lakshmanan, Anupama; et el." }, { "id": "https://authors.library.caltech.edu/records/jqx4p-9he65", "eprint_id": 85200, "eprint_status": "archive", "datestamp": "2023-08-19 09:24:36", "lastmod": "2023-10-18 17:57:31", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Vyatskikh-A", "name": { "family": "Vyatskikh", "given": "Andrey" }, "orcid": "0000-0002-6917-6931" }, { "id": "Kudo-Akira", "name": { "family": "Kudo", "given": "Akira" }, "orcid": "0000-0002-0830-5509" }, { "id": "Delalande-S", "name": { "family": "Delalande", "given": "St\u00e9phane" } }, { "id": "Greer-J-R", "name": { "family": "Greer", "given": "Julia R." }, "orcid": "0000-0002-9675-1508" } ] }, "title": "Additive Manufacturing of Polymer-Derived Titania for One-Step Solar Water Purification", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2018 Elsevier Ltd. \n\nReceived 14 June 2017, Revised 1 February 2018, Accepted 10 February 2018, Available online 7 March 2018.", "abstract": "Solar disinfection of drinking water (SODIS) is an approach for water purification widely used in households with limited access to fresh water. SODIS relies on microorganism inactivation triggered by sunlight energy in the UV spectrum and requires processing times of up to 48\u202fhr. Water treatment rate is drastically increased by using photocatalytic materials, such as TiO_2, which can harvest sunlight to promote generation of reactive oxygen species (ROS) that inactivate bacteria within few hours. One main challenge that impedes the insertion of photocatalysts in most water treatment approaches is the need to populate the catalyst particles on a three-dimensional (3D) structure with a high-surface area that is stable under water flow.", "date": "2018-06", "date_type": "published", "publication": "Materials Today Communications", "volume": "15", "publisher": "Elsevier", "pagerange": "288-293", "id_number": "CaltechAUTHORS:20180308-103302974", "issn": "2352-4928", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180308-103302974", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1016/j.mtcomm.2018.02.010", "pub_year": "2018", "author_list": "Vyatskikh, Andrey; Kudo, Akira; et el." }, { "id": "https://authors.library.caltech.edu/records/xdtgs-vwm72", "eprint_id": 86235, "eprint_status": "archive", "datestamp": "2023-08-21 23:22:17", "lastmod": "2023-10-23 15:55:06", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Belliveau-Nathan-M", "name": { "family": "Belliveau", "given": "Nathan M." }, "orcid": "0000-0002-1536-1963" }, { "id": "Barnes-Stephanie-L", "name": { "family": "Barnes", "given": "Stephanie L." }, "orcid": "0000-0002-5237-603X" }, { "id": "Ireland-William-T", "name": { "family": "Ireland", "given": "William T." }, "orcid": "0000-0003-0971-2904" }, { "id": "Jones-Daniel-L", "name": { "family": "Jones", "given": "Daniel L." }, "orcid": "0000-0002-7902-996X" }, { "id": "Sweredoski-Michael-J", "name": { "family": "Sweredoski", "given": "Michael J." }, "orcid": "0000-0003-0878-3831" }, { "id": "Moradian-Annie", "name": { "family": "Moradian", "given": "Annie" }, "orcid": "0000-0002-0407-2031" }, { "id": "Hess-Sonja", "name": { "family": "Hess", "given": "Sonja" }, "orcid": "0000-0002-5904-9816" }, { "id": "Kinney-Justin-B", "name": { "family": "Kinney", "given": "Justin B." }, "orcid": "0000-0003-1897-3778" }, { "id": "Phillips-R", "name": { "family": "Phillips", "given": "Rob" }, "orcid": "0000-0003-3082-2809" } ] }, "title": "Systematic approach for dissecting the molecular mechanisms of transcriptional regulation in bacteria", "ispublished": "pub", "full_text_status": "public", "keywords": "gene regulation; massively parallel reporter assay; quantitative models; DNA affinity chromatography; mass spectrometry", "note": "\u00a9 2018 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). \n\nEdited by Curtis G. Callan Jr., Princeton University, Princeton, NJ, and approved April 6, 2018 (received for review December 19, 2017). \n\nWe thank David Tirrell, Bradley Silverman, and Seth Lieblich for access to their Beckman Coulter MoFlo XDP cell sorter. Jost Vielmetter and Nina Budaeva provided access to their Cell Disruptor. We also thank Hernan Garcia, Manuel Razo-Mejia, Griffin Chure, Suzannah Beeler, Heun Jin Lee, Justin Bois, and Soichi Hirokawa for useful discussion. This work was supported by La Fondation Pierre-Gilles de Gennes; the Rosen Center at Caltech; NIH Grants DP1 OD000217 (Director's Pioneer Award), R01 GM085286, 1R35 GM118043-01 (Maximizing Investigators' Research Award), and 1S10RR029594-01A1; the Gordon and Betty Moore Foundation through Grant GBMF227; and the Beckman Institute. N.M.B. was supported by an HHMI International Student Research Fellowship. \n\nAuthor contributions: N.M.B., D.L.J., and R.P. designed research; N.M.B., S.L.B., D.L.J., M.J.S., A.M., S.H., and J.B.K. performed research; N.M.B., W.T.I., M.J.S., A.M., and J.B.K. analyzed data; N.M.B., S.L.B., and R.P. provided conceptualization; N.M.B., S.L.B., W.T.I., D.L.J., and J.B.K. provided methodology; N.M.B. provided investigation; N.M.B., W.T.I., D.L.J., M.J.S., and J.B.K provided software; N.M.B., W.T.I., M.J.S., and J.B.K. provided validation; S.H. and R.P. acquired funding; N.M.B., S.L.B., J.B.K., and R.P. wrote the paper. \n\nThe authors declare no conflict of interest. \n\nThis article is a PNAS Direct Submission. \n\nData deposition: Raw sequencing files have been deposited on the NCBI Sequence Read Archive, https://www.ncbi.nlm.nih.gov/sra (accession no. SRP121362) and Sort-Seq regulatory sequencing data from Escherichia coli has been deposited in NCBI BioSample, https://www.ncbi.nlm.nih.gov/biosample (accession no. SAMN07830099). Thermo RAW mass spectrometry files have been deposited in the jPOST Repository, https://repository.jpostdb.org (accession no. PXD007892). Files containing processed data and python code association with data analysis and plotting have been deposited on GitHub and Zenodo (available at https://www.github.com/RPGroup-PBoC/sortseq_belliveau and https://doi.org/10.5281/zenodo.1184169, respectively). \n\nThis article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1722055115/-/DCSupplemental.\n\nPublished - E4796.full.pdf
Submitted - 239335.full.pdf
Supplemental Material - pnas.1722055115.sapp.pdf
", "abstract": "Gene regulation is one of the most ubiquitous processes in biology. However, while the catalog of bacterial genomes continues to expand rapidly, we remain ignorant about how almost all of the genes in these genomes are regulated. At present, characterizing the molecular mechanisms by which individual regulatory sequences operate requires focused efforts using low-throughput methods. Here, we take a first step toward multipromoter dissection and show how a combination of massively parallel reporter assays, mass spectrometry, and information-theoretic modeling can be used to dissect multiple bacterial promoters in a systematic way. We show this approach on both well-studied and previously uncharacterized promoters in the enteric bacterium Escherichia coli. In all cases, we recover nucleotide-resolution models of promoter mechanism. For some promoters, including previously unannotated ones, the approach allowed us to further extract quantitative biophysical models describing input\u2013output relationships. Given the generality of the approach presented here, it opens up the possibility of quantitatively dissecting the mechanisms of promoter function in E. coli and a wide range of other bacteria.", "date": "2018-05-22", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "115", "number": "21", "publisher": "National Academy of Sciences", "pagerange": "E4796-E4805", "id_number": "CaltechAUTHORS:20180507-083945479", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180507-083945479", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "La Fondation Pierre-Gilles de Gennes" }, { "agency": "Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH", "grant_number": "DP1 OD000217" }, { "agency": "NIH", "grant_number": "R01 GM085286" }, { "agency": "NIH", "grant_number": "1R35 GM118043-01" }, { "agency": "NIH", "grant_number": "1S10RR029594-01A1" }, { "agency": "Gordon and Betty Moore Foundation", "grant_number": "GBMF227" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1073/pnas.1722055115", "pmcid": "PMC6003448", "primary_object": { "basename": "239335.full.pdf", "url": "https://authors.library.caltech.edu/records/xdtgs-vwm72/files/239335.full.pdf" }, "related_objects": [ { "basename": "E4796.full.pdf", "url": "https://authors.library.caltech.edu/records/xdtgs-vwm72/files/E4796.full.pdf" }, { "basename": "pnas.1722055115.sapp.pdf", "url": "https://authors.library.caltech.edu/records/xdtgs-vwm72/files/pnas.1722055115.sapp.pdf" } ], "pub_year": "2018", "author_list": "Belliveau, Nathan M.; Barnes, Stephanie L.; et el." }, { "id": "https://authors.library.caltech.edu/records/dvdsb-cs813", "eprint_id": 85240, "eprint_status": "archive", "datestamp": "2023-08-21 23:08:50", "lastmod": "2023-10-18 18:00:21", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Brandenberg-O-F", "name": { "family": "Brandenberg", "given": "Oliver F." }, "orcid": "0000-0001-5662-1234" }, { "id": "Prier-C-K", "name": { "family": "Prier", "given": "Christopher K." }, "orcid": "0000-0003-0902-1636" }, { "id": "Chen-Kai", "name": { "family": "Chen", "given": "Kai" }, "orcid": "0000-0002-3325-3536" }, { "id": "Knight-A-M", "name": { "family": "Knight", "given": "Anders M." }, "orcid": "0000-0001-9665-8197" }, { "id": "Wu-Zachary", "name": { "family": "Wu", "given": "Zachary" } }, { "id": "Arnold-F-H", "name": { "family": "Arnold", "given": "Frances H." }, "orcid": "0000-0002-4027-364X" } ] }, "title": "Stereoselective Enzymatic Synthesis of Heteroatom-Substituted Cyclopropanes", "ispublished": "pub", "full_text_status": "public", "keywords": "biocatalysis; carbene transfer; cyclopropanes; Cytochrome P450", "note": "\u00a9 2018 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: December 23, 2017; Revised: February 7, 2018;\nPublication Date (Web): February 24, 2018. \n\nWe thank Dr. Stephan Hammer for help with chiral separations of cyclopropylamines and all members of the Arnold Laboratory for stimulating comments and discussions. We thank Dr. David Rozzell for suggestions on cyclopropanation substrate scope. \n\nAuthor Contributions: The manuscript was written with contributions of all authors. All authors have given approval to the final version of the manuscript.\n\nThis work was supported in part by the National Science Foundation, Division of Molecular and Cellular Biosciences (Grant No. MCB-1513007) and the Defense Advanced Research Projects Agency Biological Robustness in Complex Settings Contract HR0011-15-C-0093. O.F.B. acknowledges support from the Deutsche Forschungsgemeinschaft (DFG Grant No. BR 5238/1-1) and the Swiss National Science Foundation (SNF Grant No. P300PA-171225). C.K.P. thanks the Resnick Sustainability Institute for a postdoctoral fellowship. A.M.K. and Z.W. acknowledge support from the NSF Graduate Research Fellowship (Grant No. 1745301), and A.M.K. acknowledges support from Caltech's Center for Environmental Microbial Interactions. \n\nThe authors declare no competing financial interest.\n\nPublished - acscatal.7b04423.pdf
Supplemental Material - cs7b04423_si_001.cif
Supplemental Material - cs7b04423_si_002.pdf
", "abstract": "The repurposing of hemoproteins for non-natural carbene transfer activities has generated enzymes for functions previously accessible only to chemical catalysts. With activities constrained to specific substrate classes, however, the synthetic utility of these new biocatalysts has been limited. To expand the capabilities of non-natural carbene transfer biocatalysis, we engineered variants of Cytochrome P450_(BM3) that catalyze the cyclopropanation of heteroatom-bearing alkenes, providing valuable nitrogen-, oxygen-, and sulfur-substituted cyclopropanes. Four or five active-site mutations converted a single parent enzyme into selective catalysts for the synthesis of both cis and trans heteroatom-substituted cyclopropanes, with high diastereoselectivities and enantioselectivities and up to 40\u202f000 total turnovers. This work highlights the ease of tuning hemoproteins by directed evolution for efficient cyclopropanation of new substrate classes and expands the catalytic functions of iron heme proteins.", "date": "2018-04-06", "date_type": "published", "publication": "ACS Catalysis", "volume": "8", "number": "4", "publisher": "American Chemical Society", "pagerange": "2629-2634", "id_number": "CaltechAUTHORS:20180312-085606768", "issn": "2155-5435", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180312-085606768", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "MCB-1513007" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "HR0011-15-C-0093" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "BR 5238/1-1" }, { "agency": "Swiss National Science Foundation (SNSF)", "grant_number": "P300PA-171225" }, { "agency": "Resnick Sustainability Institute" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1745301" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" } ] }, "local_group": { "items": [ { "id": "Resnick-Sustainability-Institute" }, { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1021/acscatal.7b04423", "primary_object": { "basename": "acscatal.7b04423.pdf", "url": "https://authors.library.caltech.edu/records/dvdsb-cs813/files/acscatal.7b04423.pdf" }, "related_objects": [ { "basename": "cs7b04423_si_001.cif", "url": "https://authors.library.caltech.edu/records/dvdsb-cs813/files/cs7b04423_si_001.cif" }, { "basename": "cs7b04423_si_002.pdf", "url": "https://authors.library.caltech.edu/records/dvdsb-cs813/files/cs7b04423_si_002.pdf" } ], "pub_year": "2018", "author_list": "Brandenberg, Oliver F.; Prier, Christopher K.; et el." }, { "id": "https://authors.library.caltech.edu/records/mm80w-vma28", "eprint_id": 83972, "eprint_status": "archive", "datestamp": "2023-08-19 08:26:28", "lastmod": "2023-10-20 21:52:43", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Knight-Anders-M", "name": { "family": "Knight", "given": "Anders M." }, "orcid": "0000-0001-9665-8197" }, { "id": "Kan-Sek-Buk-Jennifer", "name": { "family": "Kan", "given": "S. B. Jennifer" }, "orcid": "0000-0001-6371-8042" }, { "id": "Lewis-Russell-D", "name": { "family": "Lewis", "given": "Russell D." }, "orcid": "0000-0002-5776-7347" }, { "id": "Brandenberg-Oliver-F", "name": { "family": "Brandenberg", "given": "Oliver F." }, "orcid": "0000-0001-5662-1234" }, { "id": "Chen-Kai", "name": { "family": "Chen", "given": "Kai" }, "orcid": "0000-0002-3325-3536" }, { "id": "Arnold-F-H", "name": { "family": "Arnold", "given": "Frances H." }, "orcid": "0000-0002-4027-364X" } ] }, "title": "Diverse engineered heme proteins enable stereodivergent cyclopropanation of unactivated alkenes", "ispublished": "pub", "full_text_status": "public", "keywords": "Stereodivergence, Biocatalysis, Carbene Transfer, Heme Protein, Cyclopropanation, Directed Evolution", "note": "\u00a9 2018 American Chemical Society. ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: November 10, 2017; Publication Date (Web): February 21, 2018. \n\nThis work was supported by the National Science Foundation Division of Molecular and Cellular Biosciences (Grant MCB-1513007) and the Office of Chemical, Bioengineering, Environmental and Transport Systems SusChEM Initiative (Grant CBET-1403077). The authors thank Dr. Nathan Dalleska, Aurapat Ngamnithiporn, and Dr. Scott C. Virgil for analytical chiral GC support, and Dr. Stephan C. Hammer and Dr. Xiongyi Huang for helpful discussions and critical reading of the manuscript. A.M.K. gratefully acknowledges support from Caltech's Center for Environmental Microbial Interactions and the NSF Graduate Research Fellowship (Grant No. DGE-1745301). R.D.L. is supported by an NIH\u2013National Research Service Award training grant (5 T32 GM07616). O.F.B. acknowledges support from the Deutsche Forschungsgemeinschaft (Grant No. BR 5238/1-1) and the Swiss National Science Foundation (Grant No. P300PA-171225). A provisional patent application has been filed through the California Institute of Technology based on the results presented here. \n\nThe authors declare no competing financial interest.\n\nPublished - acscentsci.7b00548.pdf
Submitted - 20171219_Knight_ChemRxiv_submission.pdf
Supplemental Material - oc7b00548_si_001.pdf
", "abstract": "Developing catalysts that produce each stereoisomer of a desired product selectively is a longstanding synthetic challenge. Biochemists have addressed this challenge by screening nature's diversity to discover enzymes that catalyze the formation of complementary stereoisomers. We show here that the same approach can be applied to a new-to-nature enzymatic reaction, alkene cyclopropanation via carbene transfer. By screening diverse native and engineered heme proteins, we identified globins and serine-ligated \"P411\" variants of cytochromes P450 with promiscuous activity for cyclopropanation of unactivated alkene substrates. We then enhanced their activities and stereoselectivities by directed evolution: just 1\u20133 rounds of site-saturation mutagenesis and screening generated enzymes that transform unactivated alkenes and electron-deficient alkenes into each of the four stereoisomeric cyclopropanes with up to 5,400 total turnovers and 98% enantiomeric excess. These fully genetically encoded biocatalysts function in whole Escherichia coli cells in mild, aqueous conditions and provide the first example of enantioselective, intermolecular iron-catalyzed cyclopropanation of unactivated alkenes.", "date": "2018-03-28", "date_type": "published", "publication": "ACS Central Science", "volume": "4", "number": "3", "publisher": "American Chemical Society", "pagerange": "372-377", "id_number": "CaltechAUTHORS:20171220-092532762", "issn": "2374-7943", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171220-092532762", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "MCB-1513007" }, { "agency": "NSF", "grant_number": "CBET-1403077" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1745301" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "5 T32 GM07616" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "BR 5238/1-1" }, { "agency": "Swiss National Science Foundation (SNSF)", "grant_number": "P300PA-171225" } ] }, "local_group": { "items": [ { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1021/acscentsci.7b00548", "pmcid": "PMC5879470", "primary_object": { "basename": "acscentsci.7b00548.pdf", "url": "https://authors.library.caltech.edu/records/mm80w-vma28/files/acscentsci.7b00548.pdf" }, "related_objects": [ { "basename": "oc7b00548_si_001.pdf", "url": "https://authors.library.caltech.edu/records/mm80w-vma28/files/oc7b00548_si_001.pdf" }, { "basename": "20171219_Knight_ChemRxiv_submission.pdf", "url": "https://authors.library.caltech.edu/records/mm80w-vma28/files/20171219_Knight_ChemRxiv_submission.pdf" } ], "pub_year": "2018", "author_list": "Knight, Anders M.; Kan, S. B. Jennifer; et el." }, { "id": "https://authors.library.caltech.edu/records/g2nqq-42g09", "eprint_id": 84690, "eprint_status": "archive", "datestamp": "2023-08-19 07:47:33", "lastmod": "2023-10-18 16:37:18", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Vyatskikh-Andrey", "name": { "family": "Vyatskikh", "given": "Andrey" }, "orcid": "0000-0002-6917-6931" }, { "id": "Delalande-St\u00e9phane", "name": { "family": "Delalande", "given": "St\u00e9phane" } }, { "id": "Kudo-Akira", "name": { "family": "Kudo", "given": "Akira" }, "orcid": "0000-0002-0830-5509" }, { "id": "Zhang-Xuan", "name": { "family": "Zhang", "given": "Xuan" }, "orcid": "0000-0002-6155-6825" }, { "id": "Portela-Carlos-M", "name": { "family": "Portela", "given": "Carlos M." }, "orcid": "0000-0002-2649-4235" }, { "id": "Greer-J-R", "name": { "family": "Greer", "given": "Julia R." }, "orcid": "0000-0002-9675-1508" } ] }, "title": "Additive manufacturing of 3D nano-architected metals", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2018 The Authors. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. \n\nReceived: 25 September 2017 Accepted: 17 January 2018. Published online: 09 February 2018. \n\nThe authors gratefully acknowledge the financial support of JRG's Vannevar-Bush Faculty Fellowship through the Department of Defense. \n\nAuthor Contributions: A.V., S.D. and J.R.G. conceived the concept. A.V. performed synthesis, fabrication, SEM and EDS characterization. S.D. provided information on how to prepare the photoresist. A.K. performed TEM characterization and analysis. X.Z. and C.M.P. performed nanocompression experiments and analyzed the results. A.V. and J.R.G. wrote the manuscript. All authors commented on the manuscript. J.R.G. supervised the project. \n\nData availability: The data that support the findings of this study are available from the corresponding author upon reasonable request. \n\nThe authors declare no competing financial interests.\n\nPublished - s41467-018-03071-9.pdf
Supplemental Material - 41467_2018_3071_MOESM1_ESM.pdf
Supplemental Material - 41467_2018_3071_MOESM2_ESM.pdf
Supplemental Material - 41467_2018_3071_MOESM3_ESM.docx
Supplemental Material - 41467_2018_3071_MOESM4_ESM.mp4
", "abstract": "Most existing methods for additive manufacturing (AM) of metals are inherently limited to ~20\u201350\u2009\u03bcm resolution, which makes them untenable for generating complex 3D-printed metallic structures with smaller features. We developed a lithography-based process to create complex 3D nano-architected metals with ~100\u2009nm resolution. We first synthesize hybrid organic\u2013inorganic materials that contain Ni clusters to produce a metal-rich photoresist, then use two-photon lithography to sculpt 3D polymer scaffolds, and pyrolyze them to volatilize the organics, which produces a >90\u2009wt% Ni-containing architecture. We demonstrate nanolattices with octet geometries, 2\u2009\u03bcm unit cells and 300\u2013400-nm diameter beams made of 20-nm grained nanocrystalline, nanoporous Ni. Nanomechanical experiments reveal their specific strength to be 2.1\u20137.2\u2009MPa\u2009g^(\u22121)\u2009cm^3, which is comparable to lattice architectures fabricated using existing metal AM processes. This work demonstrates an efficient pathway to 3D-print micro-architected and nano-architected metals with sub-micron resolution.", "date": "2018-02-09", "date_type": "published", "publication": "Nature Communications", "volume": "9", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 593", "id_number": "CaltechAUTHORS:20180206-130051890", "issn": "2041-1723", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180206-130051890", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Vannever Bush Faculty Fellowship" } ] }, "local_group": { "items": [ { "id": "Resnick-Sustainability-Institute" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1038/s41467-018-03071-9", "pmcid": "PMC5807385", "primary_object": { "basename": "41467_2018_3071_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/g2nqq-42g09/files/41467_2018_3071_MOESM1_ESM.pdf" }, "related_objects": [ { "basename": "41467_2018_3071_MOESM2_ESM.pdf", "url": "https://authors.library.caltech.edu/records/g2nqq-42g09/files/41467_2018_3071_MOESM2_ESM.pdf" }, { "basename": "41467_2018_3071_MOESM3_ESM.docx", "url": "https://authors.library.caltech.edu/records/g2nqq-42g09/files/41467_2018_3071_MOESM3_ESM.docx" }, { "basename": "41467_2018_3071_MOESM4_ESM.mp4", "url": "https://authors.library.caltech.edu/records/g2nqq-42g09/files/41467_2018_3071_MOESM4_ESM.mp4" }, { "basename": "s41467-018-03071-9.pdf", "url": "https://authors.library.caltech.edu/records/g2nqq-42g09/files/s41467-018-03071-9.pdf" } ], "pub_year": "2018", "author_list": "Vyatskikh, Andrey; Delalande, St\u00e9phane; et el." }, { "id": "https://authors.library.caltech.edu/records/jymg9-76986", "eprint_id": 80414, "eprint_status": "archive", "datestamp": "2023-08-19 07:32:31", "lastmod": "2023-10-17 15:59:18", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Jang-Mooseok", "name": { "family": "Jang", "given": "Mooseok" }, "orcid": "0000-0003-1977-9539" }, { "id": "Horie-Yu", "name": { "family": "Horie", "given": "Yu" }, "orcid": "0000-0001-7083-1270" }, { "id": "Shibukawa-Atsushi", "name": { "family": "Shibukawa", "given": "Atsushi" } }, { "id": "Brake-Joshua-H", "name": { "family": "Brake", "given": "Joshua" }, "orcid": "0000-0002-5113-6886" }, { "id": "Liu-Yan", "name": { "family": "Liu", "given": "Yan" }, "orcid": "0000-0002-5837-4908" }, { "id": "Kamali-Seyedeh-Mahsa", "name": { "family": "Kamali", "given": "Seyedeh Mahsa" }, "orcid": "0000-0002-6968-811X" }, { "id": "Arbabi-Amir", "name": { "family": "Arbabi", "given": "Amir" }, "orcid": "0000-0001-8831-7552" }, { "id": "Ruan-Haowen", "name": { "family": "Ruan", "given": "Haowen" }, "orcid": "0000-0002-4917-4509" }, { "id": "Faraon-A", "name": { "family": "Faraon", "given": "Andrei" }, "orcid": "0000-0002-8141-391X" }, { "id": "Yang-Changhuei", "name": { "family": "Yang", "given": "Changhuei" }, "orcid": "0000-0001-8791-0354" } ] }, "title": "Wavefront shaping with disorder-engineered metasurfaces", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2018 Macmillan Publishers Limited, part of Springer Nature. \n\nReceived: 01 July 2017; Accepted: 30 November 2017; Published online: 15 January 2018. \n\nThis work was supported by the National Institutes of Health BRAIN Initiative (U01NS090577), the National Institute of Allergy and Infectious Diseases (R01AI096226), and a GIST-Caltech Collaborative Research Proposal (CG2012). Y.H. was supported by a Japan Student Services Organization (JASSO) fellowship. Y.H. and A.A. were also supported by National Science Foundation Grant 1512266 and Samsung Electronics. A.S. was supported by JSPS Overseas Research Fellowships. J.B. was supported by the National Institute of Biomedical Imaging and Bioengineering (F31EB021153) under a Ruth L. Kirschstein National Research Service Award and by the Donna and Benjamin M. Rosen Bioengineering Center. S.M.K. was supported by the DOE 'Light-Material Interactions in Energy Conversion' Energy Frontier Research Center funded by the US Department of Energy, Office of Science, Office of Basic Energy Sciences under Award no. DE-SC0001293. The device nanofabrication was performed at the Kavli Nanoscience Institute at Caltech. \n\nData availability: The data that support the plots within this paper and other findings of this study are available from the corresponding author upon reasonable request. \n\nAuthor Contributions: M.J. and Y.H. conceived the initial idea. M.J., Y.H., A.S., J.B., Y.L., H.R. and C.Y. expanded and developed the concept. M.J., Y.H. and A.S. developed theoretical modelling, designed the experiments, and analysed the experimental data. M.J. and A.S. carried out the optical focusing experiments. Y.H. performed the full-wave simulation and the design on the metasurface. A.S. performed the fluorescence imaging experiment with the help of H.R. Y.H., S.M.K. and A.A. fabricated the metasurface phase mask. Y.L. performed the measurements on the optical memory effect, the angular scattering profiles, and the stability. All authors contributed to writing the manuscript. C.Y. and A.F. supervised the project. \n\nThe authors declare no competing financial interests.\n\nAccepted Version - nihms924029.pdf
Submitted - 1706.08640.pdf
Supplemental Material - 41566_2017_78_MOESM1_ESM.pdf
", "abstract": "Recently, wavefront shaping with disordered media has demonstrated optical manipulation capabilities beyond those of conventional optics, including extended volume, aberration-free focusing and subwavelength focusing. However, translating these capabilities to useful applications has remained challenging as the input\u2013output characteristics of the disordered media (P variables) need to be exhaustively determined via O(P) measurements. Here, we propose a paradigm shift where the disorder is specifically designed so its exact input\u2013output characteristics are known a priori and can be used with only a few alignment steps. We implement this concept with a disorder-engineered metasurface, which exhibits additional unique features for wavefront shaping such as a large optical memory effect range in combination with a wide angular scattering range, excellent stability, and a tailorable angular scattering profile. Using this designed metasurface with wavefront shaping, we demonstrate high numerical aperture (NA\u2009>\u20090.5) focusing and fluorescence imaging with an estimated ~2.2\u2009\u00d7\u200910\u2078 addressable points in an ~8\u2009mm field of view.", "date": "2018-02", "date_type": "published", "publication": "Nature Photonics", "volume": "12", "number": "2", "publisher": "Nature Publishing Group", "pagerange": "84-90", "id_number": "CaltechAUTHORS:20170815-101915506", "issn": "1749-4885", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170815-101915506", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "U01NS090577" }, { "agency": "NIH", "grant_number": "R01AI096226" }, { "agency": "GIST-Caltech Research Collaboration", "grant_number": "CG2012" }, { "agency": "Japan Student Services Organization (JASSO)" }, { "agency": "NSF", "grant_number": "CBET-1512266" }, { "agency": "Samsung Electronics" }, { "agency": "Japan Society for the Promotion of Science (JSPS)" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F31EB021153" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Department of Energy (DOE)", "grant_number": "DE-SC0001293" } ] }, "local_group": { "items": [ { "id": "Kavli-Nanoscience-Institute" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1038/s41566-017-0078-z", "pmcid": "PMC5842956", "primary_object": { "basename": "41566_2017_78_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/jymg9-76986/files/41566_2017_78_MOESM1_ESM.pdf" }, "related_objects": [ { "basename": "nihms924029.pdf", "url": "https://authors.library.caltech.edu/records/jymg9-76986/files/nihms924029.pdf" }, { "basename": "1706.08640.pdf", "url": "https://authors.library.caltech.edu/records/jymg9-76986/files/1706.08640.pdf" } ], "pub_year": "2018", "author_list": "Jang, Mooseok; Horie, Yu; et el." }, { "id": "https://authors.library.caltech.edu/records/57q26-hfy77", "eprint_id": 72547, "eprint_status": "archive", "datestamp": "2023-08-19 07:20:35", "lastmod": "2023-10-23 22:42:51", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Davis-Hunter-C", "name": { "family": "Davis", "given": "Hunter C." }, "orcid": "0000-0003-1655-692X" }, { "id": "Ramesh-Pradeep", "name": { "family": "Ramesh", "given": "Pradeep" } }, { "id": "Bhatnagar-Aadyot", "name": { "family": "Bhatnagar", "given": "Aadyot" } }, { "id": "Lee-Gosselin-Audrey", "name": { "family": "Lee-Gosselin", "given": "Audrey" }, "orcid": "0000-0002-2431-2741" }, { "id": "Barry-John-F", "name": { "family": "Barry", "given": "John F." } }, { "id": "Glenn-David-R", "name": { "family": "Glenn", "given": "David R." } }, { "id": "Walsworth-Ronald-L", "name": { "family": "Walsworth", "given": "Ronald L." }, "orcid": "0000-0003-0311-4751" }, { "id": "Shapiro-M-G", "name": { "family": "Shapiro", "given": "Mikhail G." }, "orcid": "0000-0002-0291-4215" } ] }, "title": "Mapping the microscale origins of magnetic resonance image contrast with subcellular diamond magnetometry", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2018 The Authors. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. \n\nReceived: 15 April 2017. Accepted: 03 December 2017. Published online: 09 January 2018. \n\nWe acknowledge Arnab Mukherjee, George Lu, Vivek Bharadwaj, My Linh Pham, Andrei Faraon, Geoffrey Blake, Joe Kirschvink, Manuel Monge, Hans Gruber, Michael Tyszka, Russ Jacobs, and John Wood for helpful discussions. This work was supported by the National Science Foundation Graduate Research Fellowship (P.R.), Caltech Center for Environmental\u2013Microbial Interactions (M.G.S.), the Burroughs Wellcome Fund (M.G.S.), the NSF EPMD and PoLS programs (R.L.W.), and the U. S. Army Research Laboratory and the U. S. Army Research Office under contract/grant number W911NF1510548 (R.L.W.). Research in the Shapiro Laboratory is also supported by the Heritage Medical Research Institute, the Pew Scholarship in the Biomedical Sciences and the David and Lucile Packard Fellowship for Science and Engineering. \n\nHunter C. Davis and Pradeep Ramesh contributed equally to this work. \n\nAuthor Contributions: H.C.D., P.R. and M.G.S. conceived and planned the study with input from J.F.B., D.R.G. and R.L.W. H.C.D., P.R. and J.F.B. constructed the magneto-microscope. H.C.D. performed the NV magnetometry experiments and analyzed the resulting data. H.C.D., P.R. and A.L.-G. prepared the in vitro and in vivo specimens. P.R. and H.C.D. performed the MRI measurements and analyzed the resulting data. H.C.D. and A.B. developed and performed the Monte Carlo simulations. H.C.D., P.R. and M.G.S. wrote the manuscript with input from all other authors. \n\nCode availability: All the relevant software scripts are available from the authors upon request. \n\nData availability: All the relevant data are available from the authors upon request. \n\nThe authors declare no competing financial interests.\n\nPublished - s41467-017-02471-7.pdf
Submitted - 1610.01924.pdf
Supplemental Material - 41467_2017_2471_MOESM1_ESM.pdf
Supplemental Material - 41467_2017_2471_MOESM2_ESM.pdf
", "abstract": "Magnetic resonance imaging (MRI) is a widely used biomedical imaging modality that derives much of its contrast from microscale magnetic field gradients in biological tissues. However, the connection between these sub-voxel field patterns and MRI contrast has not been studied experimentally. Here, we describe a new method to map subcellular magnetic fields in mammalian cells and tissues using nitrogen vacancy diamond magnetometry and connect these maps to voxel-scale MRI contrast, providing insights for in vivo imaging and contrast agent design.", "date": "2018-01-09", "date_type": "published", "publication": "Nature Communications", "volume": "9", "publisher": "Nature Publishing Group", "pagerange": "Art. No. 131", "id_number": "CaltechAUTHORS:20161205-095517669", "issn": "2041-1723", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20161205-095517669", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF Graduate Research Fellowship" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" }, { "agency": "Burroughs Wellcome Fund" }, { "agency": "NSF" }, { "agency": "Army Research Office (ARO)" }, { "agency": "Heritage Medical Research Institute" } ] }, "local_group": { "items": [ { "id": "Heritage-Medical-Research-Institute" }, { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1038/s41467-017-02471-7", "pmcid": "PMC5760582", "primary_object": { "basename": "1610.01924.pdf", "url": "https://authors.library.caltech.edu/records/57q26-hfy77/files/1610.01924.pdf" }, "related_objects": [ { "basename": "41467_2017_2471_MOESM1_ESM.pdf", "url": "https://authors.library.caltech.edu/records/57q26-hfy77/files/41467_2017_2471_MOESM1_ESM.pdf" }, { "basename": "41467_2017_2471_MOESM2_ESM.pdf", "url": "https://authors.library.caltech.edu/records/57q26-hfy77/files/41467_2017_2471_MOESM2_ESM.pdf" }, { "basename": "s41467-017-02471-7.pdf", "url": "https://authors.library.caltech.edu/records/57q26-hfy77/files/s41467-017-02471-7.pdf" } ], "pub_year": "2018", "author_list": "Davis, Hunter C.; Ramesh, Pradeep; et el." }, { "id": "https://authors.library.caltech.edu/records/40g1k-fmd49", "eprint_id": 84222, "eprint_status": "archive", "datestamp": "2023-08-19 07:19:35", "lastmod": "2023-10-20 21:49:46", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Trivedi-Vikas", "name": { "family": "Trivedi", "given": "Vikas" }, "orcid": "0000-0003-0953-0553" }, { "id": "Choi-Harry-M-T", "name": { "family": "Choi", "given": "Harry M. T." }, "orcid": "0000-0002-1530-0773" }, { "id": "Fraser-S-E", "name": { "family": "Fraser", "given": "Scott E." }, "orcid": "0000-0002-5377-0223" }, { "id": "Pierce-N-A", "name": { "family": "Pierce", "given": "Niles A." }, "orcid": "0000-0003-2367-4406" } ] }, "title": "Multidimensional quantitative analysis of mRNA expression within intact vertebrate embryos", "ispublished": "pub", "full_text_status": "public", "keywords": "Quantitative in situ hybridization, Multiplexed in situ\nhybridization, Read-out, Read-in", "note": "\u00a9 2018 Published by The Company of Biologists Ltd. \n\nReceived July 5, 2017; Accepted November 23, 2017; Published 8 January 2018. \n\nCompeting interests: The authors declare competing financial interests in the form of patents (N.A.P. and S.E.F.), pending patent applications (N.A.P. and H.M.T.C.) and a pending startup company (N.A.P. and H.M.T.C.). \n\nAuthor contributions: Methodology: V.T., H.M.T.C., S.E.F., N.A.P.; Software: V.T.; Validation: V.T.; Investigation: V.T., H.M.T.C.; Writing - original draft: V.T., N.A.P.; Writing - review & editing: V.T., H.M.T.C., S.E.F., N.A.P.; Visualization: V.T., S.E.F., N.A.P.; Supervision: S.E.F., N.A.P.; Project administration: N.A.P.; Funding acquisition: S.E.F., N.A.P. \n\nThis work was funded by the National Institutes of Health (R01EB006192 and R01HD075605), by the Defense Advanced Research Projects Agency (HR0011-17-2-0008), by the National Science Foundation Molecular Programming Project (NSF-CCF-1317694), by the Gordon and Betty Moore Foundation (GBMF2809), by the Beckman Institute at Caltech (Programmable Molecular Technology Center, PMTC), by the Translational Imaging Center at the University of Southern California, by the Rosen Center for Bioengineering at Caltech, by the John Simon Guggenheim Memorial Foundation, by a Herchel Smith Postdoctoral Research Fellowship from the University of Cambridge, by a Professorial Fellowship at Balliol College (University of Oxford), and by the Eastman Visiting Professorship at the University of Oxford. Deposited in PMC for release after 12 months.\n\nPublished - dev156869.full.pdf
Submitted - 214619.full.pdf
Supplemental Material - DEV156869supp.pdf
", "abstract": "For decades, in situ hybridization methods have been essential tools for studies of vertebrate development and disease, as they enable qualitative analyses of mRNA expression in an anatomical context. Quantitative mRNA analyses typically sacrifice the anatomy, relying on embryo microdissection, dissociation, cell sorting and/or homogenization. Here, we eliminate the trade-off between quantitation and anatomical context, using quantitative in situ hybridization chain reaction (qHCR) to perform accurate and precise relative quantitation of mRNA expression with subcellular resolution within whole-mount vertebrate embryos. Gene expression can be queried in two directions: read-out from anatomical space to expression space reveals co-expression relationships in selected regions of the specimen; conversely, read-in from multidimensional expression space to anatomical space reveals those anatomical locations in which selected gene co-expression relationships occur. As we demonstrate by examining gene circuits underlying somitogenesis, quantitative read-out and read-in analyses provide the strengths of flow cytometry expression analyses, but by preserving subcellular anatomical context, they enable bi-directional queries that open a new era for in situ hybridization.", "date": "2018-01-08", "date_type": "published", "publication": "Development", "volume": "145", "number": "1", "publisher": "Company of Biologists", "pagerange": "Art. No. 156869", "id_number": "CaltechAUTHORS:20180110-083122477", "issn": "0950-1991", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20180110-083122477", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01EB006192" }, { "agency": "NIH", "grant_number": "R01HD075605" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "HR0011-17-2-0008" }, { "agency": "NSF", "grant_number": "CCF-1317694" }, { "agency": "Gordon and Betty Moore Foundation", "grant_number": "GBMF2809" }, { "agency": "Caltech Beckman Institute" }, { "agency": "University of Southern California" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "John Simon Guggenheim Memorial Foundation" }, { "agency": "University of Cambridge" }, { "agency": "University of Oxford" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1242/dev.156869", "pmcid": "PMC5825878", "primary_object": { "basename": "214619.full.pdf", "url": "https://authors.library.caltech.edu/records/40g1k-fmd49/files/214619.full.pdf" }, "related_objects": [ { "basename": "DEV156869supp.pdf", "url": "https://authors.library.caltech.edu/records/40g1k-fmd49/files/DEV156869supp.pdf" }, { "basename": "dev156869.full.pdf", "url": "https://authors.library.caltech.edu/records/40g1k-fmd49/files/dev156869.full.pdf" } ], "pub_year": "2018", "author_list": "Trivedi, Vikas; Choi, Harry M. T.; et el." }, { "id": "https://authors.library.caltech.edu/records/p04pt-mv098", "eprint_id": 83033, "eprint_status": "archive", "datestamp": "2023-08-19 06:16:54", "lastmod": "2023-10-17 22:52:08", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ruan-Haowen", "name": { "family": "Ruan", "given": "Haowen" }, "orcid": "0000-0002-4917-4509" }, { "id": "Brake-Joshua-H", "name": { "family": "Brake", "given": "Joshua" }, "orcid": "0000-0002-5113-6886" }, { "id": "Robinson-J-Elliott", "name": { "family": "Robinson", "given": "J. Elliott" }, "orcid": "0000-0001-9417-3938" }, { "id": "Liu-Yan", "name": { "family": "Liu", "given": "Yan" }, "orcid": "0000-0002-5837-4908" }, { "id": "Jang-Mooseok", "name": { "family": "Jang", "given": "Mooseok" }, "orcid": "0000-0003-1977-9539" }, { "id": "Xiao-Cheng", "name": { "family": "Xiao", "given": "Cheng" }, "orcid": "0000-0001-9649-7450" }, { "id": "Zhou-Chunyi", "name": { "family": "Zhou", "given": "Chunyi" } }, { "id": "Gradinaru-V", "name": { "family": "Gradinaru", "given": "Viviana" }, "orcid": "0000-0001-5868-348X" }, { "id": "Yang-Changhuei", "name": { "family": "Yang", "given": "Changhuei" }, "orcid": "0000-0001-8791-0354" } ] }, "title": "Deep tissue optical focusing and optogenetic modulation with time-reversed ultrasonically encoded light", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). \n\nSubmitted 2 August 2017; Accepted 8 November 2017; Published 8 December 2017. \n\nWe would like to thank B. Yang, L. Bremner, A. Shibukawa, and H. Deng for their assistance and helpful discussions. Funding: We would like to acknowledge support from the NIH (DP2OD007307 to C.Y., U01NS090577 to C.Y. and V.G., and F31EB021153 to J.B.), the Gwangju Institute of Science and Technology\u2013California Institute of Technology (Caltech) Collaborative Research Program (CG2012 to C.Y.), the Children's Tumor Foundation (2016-01-006 to J.E.R.), the Donna and Benjamin M. Rosen Bioengineering Center (to J.B.), the Heritage Medical Research Institute (to V.G.), and the Tianqiao and Chrissy Chen Institute for Neuroscience at Caltech (to V.G.). Author contributions: H.R. and J.B. contributed equally to the work. H.R. designed the experimental setup. H.R., J.B., M.J., and Y.L. conducted the optical experiments. J.E.R., C.X., and C.Z. prepared the biological samples. J.E.R., J.B., C.X., and C.Z. conducted the electrophysiological recordings. H.R., J.B., Y.L., and J.E.R. analyzed the experimental data. V.G. and C.Y. supervised the project. All authors contributed to the manuscript preparation. Competing interests: C.Y. is an author on a patent related to this work (publication no. US9313423 B2, filed on 27 March 2013). The authors declare that they have no other competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.\n\nPublished - eaao5520.full.pdf
Supplemental Material - aao5520_SM.pdf
", "abstract": "Noninvasive light focusing deep inside living biological tissue has long been a goal in biomedical optics. However, the optical scattering of biological tissue prevents conventional optical systems from tightly focusing visible light beyond several hundred micrometers. The recently developed wavefront shaping technique time-reversed ultrasonically encoded (TRUE) focusing enables noninvasive light delivery to targeted locations beyond the optical diffusion limit. However, until now, TRUE focusing has only been demonstrated inside nonliving tissue samples. We present the first example of TRUE focusing in 2-mm-thick living brain tissue and demonstrate its application for optogenetic modulation of neural activity in 800-\u03bcm-thick acute mouse brain slices at a wavelength of 532 nm. We found that TRUE focusing enabled precise control of neuron firing and increased the spatial resolution of neuronal excitation fourfold when compared to conventional lens focusing. This work is an important step in the application of TRUE focusing for practical biomedical uses.", "date": "2017-12", "date_type": "published", "publication": "Science Advances", "volume": "3", "number": "12", "publisher": "American Association for the Advancement of Science", "pagerange": "Art. No. eaao5520", "id_number": "CaltechAUTHORS:20171107-132336726", "issn": "2375-2548", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171107-132336726", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "DP2OD007307" }, { "agency": "NIH", "grant_number": "U01NS090577" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "F31EB021153" }, { "agency": "GIST-Caltech Research Collaboration", "grant_number": "CG2012" }, { "agency": "Children's Tumor Foundation", "grant_number": "2016-01-006" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Heritage Medical Research Institute" }, { "agency": "Tianqiao and Chrissy Chen Institute for Neuroscience" } ] }, "local_group": { "items": [ { "id": "Heritage-Medical-Research-Institute" }, { "id": "Tianqiao-and-Chrissy-Chen-Institute-for-Neuroscience" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1126/sciadv.aao5520", "pmcid": "PMC5722648", "primary_object": { "basename": "aao5520_SM.pdf", "url": "https://authors.library.caltech.edu/records/p04pt-mv098/files/aao5520_SM.pdf" }, "related_objects": [ { "basename": "eaao5520.full.pdf", "url": "https://authors.library.caltech.edu/records/p04pt-mv098/files/eaao5520.full.pdf" } ], "pub_year": "2017", "author_list": "Ruan, Haowen; Brake, Joshua; et el." }, { "id": "https://authors.library.caltech.edu/records/595k8-ysd50", "eprint_id": 83789, "eprint_status": "archive", "datestamp": "2023-08-19 06:06:33", "lastmod": "2023-10-17 23:30:33", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Ruan-Haowen", "name": { "family": "Ruan", "given": "Haowen" }, "orcid": "0000-0002-4917-4509" }, { "id": "Haber-Tom", "name": { "family": "Haber", "given": "Tom" } }, { "id": "Liu-Yan", "name": { "family": "Liu", "given": "Yan" }, "orcid": "0000-0002-5837-4908" }, { "id": "Brake-Joshua-H", "name": { "family": "Brake", "given": "Joshua" }, "orcid": "0000-0002-5113-6886" }, { "id": "Kim-Jinho", "name": { "family": "Kim", "given": "Jinho" }, "orcid": "0000-0001-8711-960X" }, { "id": "Berlin-Jacob-M", "name": { "family": "Berlin", "given": "Jacob M." }, "orcid": "0000-0001-7498-766X" }, { "id": "Yang-Changhuei", "name": { "family": "Yang", "given": "Changhuei" }, "orcid": "0000-0001-8791-0354" } ] }, "title": "Focusing light inside scattering media with magnetic-particle-guided wavefront shaping", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 Optical Society of America. \n\nReceived 21 August 2017; revised 27 September 2017; accepted 28 September 2017 (Doc. ID 305214); published 25 October 2017. \n\nFunding: National Institutes of Health (NIH) (F31EB021153, U01NS090577); GIST-Caltech Collaborative Research Proposal (CG2016); Donna and Benjamin M. Rosen Bioengineering Center; Israel-City of Hope Fellowship Program in Biomedical Research. \n\nThe authors would like to thank Dr. Euiheon Chung, Dr. Mooseok Jang, Dr. Ethan White, Dr. Kathleen Elison, Dr. Mikhail Shapiro, Dr. George Lu, and Mr. Hunter Davis for assistance and helpful discussions. TEM imaging was conducted at the Electron Microscopy core at City of Hope with Marcia Millier, Zhuo Li and Ricardo Zerda.\n\nPublished - optica-4-11-1337.pdf
Accepted Version - nihms926729.pdf
Supplemental Material - 3081181.pdf
Supplemental Material - SuppVideo1_MagBeads25Hz.avi
Supplemental Material - SuppVideo2_MagBeads5Hz.avi
Supplemental Material - SuppVideo3_Cell25Hz.avi
Supplemental Material - SuppVideo4_Cell5Hz.avi
", "abstract": "Optical scattering has traditionally limited the ability to focus light inside scattering media such as biological tissue. Recently developed wavefront shaping techniques promise to overcome this limit by tailoring an optical wavefront to constructively interfere at a target location deep inside scattering media. To find such a wavefront solution, a \"guidestar\" mechanism is required to identify the target location. However, developing guidestars of practical usefulness is challenging, especially in biological tissue, which hinders the translation of wavefront shaping techniques. Here, we demonstrate a guidestar mechanism that relies on magnetic modulation of small particles. This guidestar method features an optical modulation efficiency of 29% and enables micrometer-scale focusing inside biological tissue with a peak intensity-to-background ratio (PBR) of 140; both numbers are one order of magnitude higher than those achieved with the ultrasound guidestar, a popular guidestar method. We also demonstrate that light can be focused on cells labeled with magnetic particles, and to different target locations by magnetically controlling the position of a particle. Since magnetic fields have a large penetration depth even through bone structures like the skull, this optical focusing method holds great promise for deep-tissue applications such as optogenetic modulation of neurons, targeted light-based therapy, and imaging.", "date": "2017-11-20", "date_type": "published", "publication": "Optica", "volume": "4", "number": "11", "publisher": "Optical Society of America", "pagerange": "1337-1343", "id_number": "CaltechAUTHORS:20171211-091117607", "issn": "2334-2536", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171211-091117607", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Predoctoral Fellowship", "grant_number": "F31EB021153" }, { "agency": "NIH", "grant_number": "U01NS090577" }, { "agency": "GIST-Caltech Research Collaboration", "grant_number": "CG2016" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Israel-City of Hope Fellowship Program in Biomedical Research" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1364/OPTICA.4.001337", "pmcid": "PMC5881932", "primary_object": { "basename": "nihms926729.pdf", "url": "https://authors.library.caltech.edu/records/595k8-ysd50/files/nihms926729.pdf" }, "related_objects": [ { "basename": "optica-4-11-1337.pdf", "url": "https://authors.library.caltech.edu/records/595k8-ysd50/files/optica-4-11-1337.pdf" }, { "basename": "3081181.pdf", "url": "https://authors.library.caltech.edu/records/595k8-ysd50/files/3081181.pdf" }, { "basename": "SuppVideo1_MagBeads25Hz.avi", "url": "https://authors.library.caltech.edu/records/595k8-ysd50/files/SuppVideo1_MagBeads25Hz.avi" }, { "basename": "SuppVideo2_MagBeads5Hz.avi", "url": "https://authors.library.caltech.edu/records/595k8-ysd50/files/SuppVideo2_MagBeads5Hz.avi" }, { "basename": "SuppVideo3_Cell25Hz.avi", "url": "https://authors.library.caltech.edu/records/595k8-ysd50/files/SuppVideo3_Cell25Hz.avi" }, { "basename": "SuppVideo4_Cell5Hz.avi", "url": "https://authors.library.caltech.edu/records/595k8-ysd50/files/SuppVideo4_Cell5Hz.avi" } ], "pub_year": "2017", "author_list": "Ruan, Haowen; Haber, Tom; et el." }, { "id": "https://authors.library.caltech.edu/records/my3wd-7zq33", "eprint_id": 83283, "eprint_status": "archive", "datestamp": "2023-08-19 05:55:23", "lastmod": "2023-10-23 15:07:27", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Qureshi-Muhammad-Mohsin", "name": { "family": "Qureshi", "given": "Muhammad Mohsin" }, "orcid": "0000-0003-0362-0144" }, { "id": "Brake-Joshua-H", "name": { "family": "Brake", "given": "Joshua" }, "orcid": "0000-0002-5113-6886" }, { "id": "Jeon-Hee-Jae", "name": { "family": "Jeon", "given": "Hee-Jae" } }, { "id": "Ruan-Haowen", "name": { "family": "Ruan", "given": "Haowen" }, "orcid": "0000-0002-4917-4509" }, { "id": "Liu-Yan", "name": { "family": "Liu", "given": "Yan" }, "orcid": "0000-0002-5837-4908" }, { "id": "Safi-Abdul-Mohaimen", "name": { "family": "Safi", "given": "Abdul Mohaimen" }, "orcid": "0000-0003-1117-0286" }, { "id": "Eom-Tae-Joong", "name": { "family": "Eom", "given": "Tae Joong" }, "orcid": "0000-0003-0556-4027" }, { "id": "Yang-Changhuei", "name": { "family": "Yang", "given": "Changhuei" }, "orcid": "0000-0001-8791-0354" }, { "id": "Chung-Euiheon", "name": { "family": "Chung", "given": "Euiheon" }, "orcid": "0000-0002-3326-6927" } ] }, "title": "In vivo study of optical speckle decorrelation time across depths in the mouse brain", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 Optical Society of America. \n\nReceived 16 Aug 2017; revised 10 Sep 2017; accepted 25 Sep 2017; published 4 Oct 2017. \n\nDisclosures: The authors declare that there are no conflicts of interest related to this article. \n\nThis work was supported in part by GIST Research Institute (GRI), and the GIST-Caltech Research Collaboration Project through a grant provided by GIST in 2017, a research grant (NRF-2016R1A2B4015381), the Brain Research Program (NRF-2017M3C7A 1044964) of the National Research Foundation (NRF), the KBRI basic research program through Korea Brain Research Institute (17-BR-04) funded by the Ministry of Science, ICT, Future Planning, the industrial convergence foundation construction program (N0002310) funded by the Ministry of Trade, Industry & Energy, and the National Institutes of Health (NIH) (U01NS090577). J.B. was supported by the National Institute of Biomedical Imaging, and Bioengineering (F31EB021153) under a Ruth L. Kirschstein National Research Service Award and by the Donna and Benjamin M. Rosen Bioengineering Center. \n\nThe authors thank Ms. Ji Hye Yang from GIST for her help during the animal experiment.\n\nThe last sentence of the 2nd paragraph of section \"4. Results\" should read: \"The respective mean decorrelation times for 1.1, 1.8, 2.5, and 3.2 mm depth of point-like source are 5.3, 1.5, 0.37, and 0.26 ms, with standard deviations of 4.8, 1.6, 0.16, 0.13 ms.\" instead of the version in the manuscript (copied below) which contains incorrect values. \"The respective mean decorrelation times for 1.1, 1.8, 2.5, and 3.2 mm depth of point-like source are 7.5, 3.5, 1.1, and 0.6 ms, with standard deviations of 5.9, 2.4, 0.6, and 0.3 ms.\"\n\nPublished - boe-8-11-4855.pdf
Erratum - boe-8-11-5039_errtm.pdf
", "abstract": "The strong optical scattering of biological tissue confounds our ability to focus light deeply into the brain beyond depths of a few hundred microns. This challenge can be potentially overcome by exploiting wavefront shaping techniques which allow light to be focused through or inside scattering media. However, these techniques require the scattering medium to be static, as changes in the arrangement of the scatterers between the wavefront recording and playback steps reduce the fidelity of the focus that is formed. Furthermore, as the thickness of the scattering medium increases, the influence of the dynamic nature becomes more severe due to the growing number of scattering events experienced by each photon. In this paper, by examining the scattering dynamics in the mouse brain in vivo via multispeckle diffusing wave spectroscopy (MSDWS) using a custom fiber probe that simulates a point-like source within the brain, we investigate the relationship between this decorrelation time and the depth of the point-like light source inside the living mouse brain at depths up to 3.2 mm.", "date": "2017-11-01", "date_type": "published", "publication": "Biomedical Optics Express", "volume": "8", "number": "11", "publisher": "Optical Society of America", "pagerange": "4855-4864", "id_number": "CaltechAUTHORS:20171117-083356029", "issn": "2156-7085", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171117-083356029", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "GIST Research Institute (GRI)" }, { "agency": "GIST-Caltech Research Collaboration Project" }, { "agency": "National Research Foundation of Korea", "grant_number": "NRF-2016R1A2B4015381" }, { "agency": "National Research Foundation of Korea", "grant_number": "NRF-2017M3C7A 1044964" }, { "agency": "Ministry of Science, ICT, Future Planning (Korea)", "grant_number": "17-BR-04" }, { "agency": "Ministry of Trade, Industry and Energy (Korea)", "grant_number": "N0002310" }, { "agency": "NIH", "grant_number": "U01NS090577" }, { "agency": "NIH", "grant_number": "F31EB021153" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1364/BOE.8.004855", "pmcid": "PMC5695936", "primary_object": { "basename": "boe-8-11-4855.pdf", "url": "https://authors.library.caltech.edu/records/my3wd-7zq33/files/boe-8-11-4855.pdf" }, "related_objects": [ { "basename": "boe-8-11-5039_errtm.pdf", "url": "https://authors.library.caltech.edu/records/my3wd-7zq33/files/boe-8-11-5039_errtm.pdf" } ], "pub_year": "2017", "author_list": "Qureshi, Muhammad Mohsin; Brake, Joshua; et el." }, { "id": "https://authors.library.caltech.edu/records/ptv4z-1sb38", "eprint_id": 82781, "eprint_status": "archive", "datestamp": "2023-08-19 05:43:37", "lastmod": "2023-10-23 15:06:10", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Bedbrook-C-N", "name": { "family": "Bedbrook", "given": "Claire N." }, "orcid": "0000-0003-3973-598X" }, { "id": "Yang-Kevin-K", "name": { "family": "Yang", "given": "Kevin K." }, "orcid": "0000-0001-9045-6826" }, { "id": "Rice-A-J", "name": { "family": "Rice", "given": "Austin J." } }, { "id": "Gradinaru-V", "name": { "family": "Gradinaru", "given": "Viviana" }, "orcid": "0000-0001-5868-348X" }, { "id": "Arnold-F-H", "name": { "family": "Arnold", "given": "Frances H." }, "orcid": "0000-0002-4027-364X" } ] }, "title": "Machine learning to design integral membrane channelrhodopsins for efficient eukaryotic expression and plasma membrane localization", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 Bedbrook et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. \n\nReceived: August 9, 2017; Accepted: September 21, 2017; Published: October 23, 2017. \n\nWe thank Twist Bioscience for synthesizing and cloning ChR sequences as part of their \u03b1 and \u03b2 manufacturing programs. We thank the Gradinaru and Arnold labs for helpful discussions. We also thank Dr. John Bedbrook for critical reading of the manuscript. Imaging was performed in the Biological Imaging Facility, with the support of the Caltech Beckman Institute and the Arnold and Mabel Beckman Foundation. \n\nData Availability: All relevant data are either within the paper and its Supporting Information files or published in ref 5. \n\nThis work is funded by the National Institute for Mental Health R21MH103824 (VG and FHA) and the Institute for Collaborative Biotechnologies through grant number W911F-09-0001 from the U.S. Army Research Office (FHA). The content is solely the responsibility of the authors and does not necessarily reflect the position or policy of the National Center for Research Resources, the National Institutes of Health, or the Government, and no official endorsement should be inferred. VG is a Heritage Principal Investigator supported by the Heritage Medical Research Institute. CNB and AJR are funded by Ruth L. Kirschstein National Research Service Awards (F31MH102913 and F32GM116319, respectively). KKY is a trainee in the Caltech Biotechnology Leadership Program, and has received financial support from the Donna and Benjamin M. Rosen Bioengineering Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. \n\nAuthors declare no competing interests. \n\nAuthor Contributions:\nConceptualization: Claire N. Bedbrook, Kevin K. Yang, Austin J. Rice, Viviana Gradinaru,\nFrances H. Arnold.\nFormal analysis: Claire N. Bedbrook, Kevin K. Yang.\nMethodology: Claire N. Bedbrook, Kevin K. Yang, Austin J. Rice.\nProject administration: Frances H. Arnold.\nSoftware: Claire N. Bedbrook, Kevin K. Yang.\nSupervision: Viviana Gradinaru, Frances H. Arnold.\nVisualization: Claire N. Bedbrook, Kevin K. Yang, Austin J. Rice.\nWriting \u00b1 original draft: Claire N. Bedbrook, Kevin K. Yang.\nWriting \u00b1 review & editing: Claire N. Bedbrook, Kevin K. Yang, Austin J. Rice, Viviana Gradinaru,\nFrances H. Arnold.\n\nPublished - journal.pcbi.1005786.pdf
Supplemental Material - journal.pcbi.1005786.s001.csv
Supplemental Material - journal.pcbi.1005786.s002.tif
Supplemental Material - journal.pcbi.1005786.s003.tif
Supplemental Material - journal.pcbi.1005786.s004.tif
Supplemental Material - journal.pcbi.1005786.s005.tif
Supplemental Material - journal.pcbi.1005786.s006.tif
Supplemental Material - journal.pcbi.1005786.s007.tif
Supplemental Material - journal.pcbi.1005786.s008.tif
Supplemental Material - journal.pcbi.1005786.s009.tif
Supplemental Material - journal.pcbi.1005786.s010.tif
Supplemental Material - journal.pcbi.1005786.s011.tif
Supplemental Material - journal.pcbi.1005786.s012.tif
Supplemental Material - journal.pcbi.1005786.s013.tif
", "abstract": "There is growing interest in studying and engineering integral membrane proteins (MPs) that play key roles in sensing and regulating cellular response to diverse external signals. A MP must be expressed, correctly inserted and folded in a lipid bilayer, and trafficked to the proper cellular location in order to function. The sequence and structural determinants of these processes are complex and highly constrained. Here we describe a predictive, machine-learning approach that captures this complexity to facilitate successful MP engineering and design. Machine learning on carefully-chosen training sequences made by structure-guided SCHEMA recombination has enabled us to accurately predict the rare sequences in a diverse library of channelrhodopsins (ChRs) that express and localize to the plasma membrane of mammalian cells. These light-gated channel proteins of microbial origin are of interest for neuroscience applications, where expression and localization to the plasma membrane is a prerequisite for function. We trained Gaussian process (GP) classification and regression models with expression and localization data from 218 ChR chimeras chosen from a 118,098-variant library designed by SCHEMA recombination of three parent ChRs. We use these GP models to identify ChRs that express and localize well and show that our models can elucidate sequence and structure elements important for these processes. We also used the predictive models to convert a naturally occurring ChR incapable of mammalian localization into one that localizes well.", "date": "2017-10-23", "date_type": "published", "publication": "PLOS Computational Biology", "volume": "13", "number": "10", "publisher": "Public Library of Science", "pagerange": "Art. No. e1005786", "id_number": "CaltechAUTHORS:20171030-140148566", "issn": "1553-7358", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20171030-140148566", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R21MH103824" }, { "agency": "Army Research Office (ARO)", "grant_number": "W911F-09-0001" }, { "agency": "Heritage Medical Research Institute" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "F31MH102913" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "F32GM116319" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Arnold and Mabel Beckman Foundation" } ] }, "local_group": { "items": [ { "id": "Heritage-Medical-Research-Institute" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1371/journal.pcbi.1005786", "pmcid": "PMC5695628", "primary_object": { "basename": "journal.pcbi.1005786.s012.tif", "url": "https://authors.library.caltech.edu/records/ptv4z-1sb38/files/journal.pcbi.1005786.s012.tif" }, "related_objects": [ { "basename": "journal.pcbi.1005786.s004.tif", "url": "https://authors.library.caltech.edu/records/ptv4z-1sb38/files/journal.pcbi.1005786.s004.tif" }, { "basename": "journal.pcbi.1005786.s006.tif", "url": "https://authors.library.caltech.edu/records/ptv4z-1sb38/files/journal.pcbi.1005786.s006.tif" }, { "basename": "journal.pcbi.1005786.s007.tif", "url": "https://authors.library.caltech.edu/records/ptv4z-1sb38/files/journal.pcbi.1005786.s007.tif" }, { "basename": "journal.pcbi.1005786.s008.tif", "url": "https://authors.library.caltech.edu/records/ptv4z-1sb38/files/journal.pcbi.1005786.s008.tif" }, { "basename": "journal.pcbi.1005786.s009.tif", "url": "https://authors.library.caltech.edu/records/ptv4z-1sb38/files/journal.pcbi.1005786.s009.tif" }, { "basename": "journal.pcbi.1005786.s010.tif", "url": "https://authors.library.caltech.edu/records/ptv4z-1sb38/files/journal.pcbi.1005786.s010.tif" }, { "basename": "journal.pcbi.1005786.s011.tif", "url": "https://authors.library.caltech.edu/records/ptv4z-1sb38/files/journal.pcbi.1005786.s011.tif" }, { "basename": "journal.pcbi.1005786.s001.csv", "url": "https://authors.library.caltech.edu/records/ptv4z-1sb38/files/journal.pcbi.1005786.s001.csv" }, { "basename": "journal.pcbi.1005786.s002.tif", "url": "https://authors.library.caltech.edu/records/ptv4z-1sb38/files/journal.pcbi.1005786.s002.tif" }, { "basename": "journal.pcbi.1005786.s005.tif", "url": "https://authors.library.caltech.edu/records/ptv4z-1sb38/files/journal.pcbi.1005786.s005.tif" }, { "basename": "journal.pcbi.1005786.pdf", "url": "https://authors.library.caltech.edu/records/ptv4z-1sb38/files/journal.pcbi.1005786.pdf" }, { "basename": "journal.pcbi.1005786.s003.tif", "url": "https://authors.library.caltech.edu/records/ptv4z-1sb38/files/journal.pcbi.1005786.s003.tif" }, { "basename": "journal.pcbi.1005786.s013.tif", "url": "https://authors.library.caltech.edu/records/ptv4z-1sb38/files/journal.pcbi.1005786.s013.tif" } ], "pub_year": "2017", "author_list": "Bedbrook, Claire N.; Yang, Kevin K.; et el." }, { "id": "https://authors.library.caltech.edu/records/k8ast-xev62", "eprint_id": 81405, "eprint_status": "archive", "datestamp": "2023-08-19 05:36:05", "lastmod": "2023-10-17 19:49:50", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Obana-Maiko", "name": { "family": "Obana", "given": "Maiko" }, "orcid": "0000-0003-4150-0055" }, { "id": "Silverman-Bradley-R", "name": { "family": "Silverman", "given": "Bradley R." }, "orcid": "0000-0002-9256-8941" }, { "id": "Tirrell-D-A", "name": { "family": "Tirrell", "given": "David A." }, "orcid": "0000-0003-3175-4596" } ] }, "title": "Protein-Mediated Colloidal Assembly", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 American Chemical Society. \n\nReceived: August 1, 2017; Published: September 12, 2017. \n\nWe thank Trudy Padmore for technical assistance with particle conjugation and Andres Collazo for assistance with confocal microscopy. This work was supported by Defense Advanced Research Projects Agency Biological Robustness in Complex Settings Contract HR001-15-C-0093. M.O is supported by the Nakajima Foundation. B.S. is supported by NIH Training Grant 1T32GM112592 and by the Rosen Center for Bioengineering. Imaging was performed in the Biological Imaging Facility, with the support of the Caltech Beckman Institute and the Arnold and Mabel Beckman Foundation. \n\nAuthor Contributions: M.O and B.R.S. contributed equally to this work. \n\nThe authors declare the absence of any competing financial interests.\n\nAccepted Version - nihms914383.pdf
Supplemental Material - ja7b07798_si_001.pdf
", "abstract": "Programmable colloidal assembly enables the creation of mesoscale materials in a bottom-up manner. Although DNA oligonucleotides have been used extensively as the programmable units in this paradigm, proteins, which exhibit more diverse modes of association and function, have not been widely used to direct colloidal assembly. Here we use protein\u2013protein interactions to drive controlled aggregation of polystyrene microparticles, either through reversible coiled-coil interactions or through intermolecular isopeptide linkages. The sizes of the resulting aggregates are tunable and can be controlled by the concentration of immobilized surface proteins. Moreover, particles coated with different protein pairs undergo orthogonal assembly. We demonstrate that aggregates formed by association of coiled-coil proteins, in contrast to those linked by isopeptide bonds, are dispersed by treatment with chemical denaturants or soluble competing proteins. Finally, we show that protein\u2013protein interactions can be used to assemble complex core\u2013shell aggregates. This work illustrates a versatile strategy for engineering colloidal systems for use in materials science and biotechnology.", "date": "2017-10-11", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "139", "number": "40", "publisher": "American Chemical Society", "pagerange": "14251-14256", "id_number": "CaltechAUTHORS:20170913-101124804", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170913-101124804", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "HR001-15-C-0093" }, { "agency": "Nakajima Foundation" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "1T32GM112592" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Arnold and Mabel Beckman Foundation" } ] }, "collection": "CaltechAUTHORS", "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center", "value": "Rosen Bioengineering Center" } ] }, "doi": "10.1021/jacs.7b07798", "pmcid": "PMC5672941", "primary_object": { "basename": "ja7b07798_si_001.pdf", "url": "https://authors.library.caltech.edu/records/k8ast-xev62/files/ja7b07798_si_001.pdf" }, "related_objects": [ { "basename": "nihms914383.pdf", "url": "https://authors.library.caltech.edu/records/k8ast-xev62/files/nihms914383.pdf" } ], "pub_year": "2017", "author_list": "Obana, Maiko; Silverman, Bradley R.; et el." }, { "id": "https://authors.library.caltech.edu/records/79ffp-qyg97", "eprint_id": 77531, "eprint_status": "archive", "datestamp": "2023-08-19 05:15:12", "lastmod": "2023-10-25 23:08:32", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lakshmanan-Anupama", "name": { "family": "Lakshmanan", "given": "Anupama" }, "orcid": "0000-0002-6702-837X" }, { "id": "Lu-George-Jiaozhi", "name": { "family": "Lu", "given": "George J." }, "orcid": "0000-0002-4689-9686" }, { "id": "Farhadi-Arash", "name": { "family": "Farhadi", "given": "Arash" }, "orcid": "0000-0001-9137-8559" }, { "id": "Nety-Suchita-P", "name": { "family": "Nety", "given": "Suchita P." } }, { "id": "Kunth-Martin", "name": { "family": "Kunth", "given": "Martin" }, "orcid": "0000-0002-9741-9881" }, { "id": "Lee-Gosselin-Audrey", "name": { "family": "Lee-Gosselin", "given": "Audrey" }, "orcid": "0000-0002-2431-2741" }, { "id": "Maresca-David", "name": { "family": "Maresca", "given": "David" }, "orcid": "0000-0002-4921-6406" }, { "id": "Bourdeau-Raymond-W", "name": { "family": "Bourdeau", "given": "Raymond W." }, "orcid": "0000-0003-2202-1980" }, { "id": "Yin-Melissa", "name": { "family": "Yin", "given": "Melissa" } }, { "id": "Yan-Judy", "name": { "family": "Yan", "given": "Judy" } }, { "id": "Witte-Chistopher", "name": { "family": "Witte", "given": "Christopher" }, "orcid": "0000-0002-4098-6623" }, { "id": "Malounda-Dina", "name": { "family": "Malounda", "given": "Dina" }, "orcid": "0000-0001-7086-9877" }, { "id": "Foster-F-Stuart", "name": { "family": "Foster", "given": "F. Stuart" } }, { "id": "Schr\u00f6der-Leif", "name": { "family": "Schr\u00f6der", "given": "Leif" }, "orcid": "0000-0003-4901-0325" }, { "id": "Shapiro-M-G", "name": { "family": "Shapiro", "given": "Mikhail G." }, "orcid": "0000-0002-0291-4215" } ] }, "title": "Preparation of biogenic gas vesicle nanostructures for use as contrast agents for ultrasound and MRI", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 Macmillan Publishers Limited, part of Springer Nature. \n\nPublished online 07 September 2017. \n\nThis research was supported by the National Institutes of Health (R01-EB018975 to M.G.S.), DARPA (W911NF-14-1-0111 to M.G.S.), CIHR (grant no. FDN148367 to F.S.F.) and HFSP (RGP0050/2016 to M.G.S. and L.S.). A.L. is supported by an NSF graduate research fellowship (no. 1144469). A.F. is supported by an NSERC graduate fellowship. S.P.N. is supported by a Caltech Summer Undergraduate Research Fellowship. D. Maresca is supported by an HFSP Cross-Disciplinary Postdoctoral Fellowship. Research in the Shapiro laboratory is also supported by the Heritage Medical Research Institute, the Burroughs Wellcome Fund, the Pew Charitable Trust, the Sontag Foundation and the David and Lucile Packard Foundation. Research in the Schr\u00f6der laboratory is also supported by the Michael J. Fox Foundation for Parkinson's Research (no. 12549) and a Koselleck Grant by the German Research Foundation (DFG; project SCHR 995/5-1). We acknowledge the Jensen Lab and the Beckman Resource Center for Electron Microscopy (EM) at the California Institute of Technology for technical guidance and for allowing us to use their resources. The EM facility is funded by the Beckman Foundation, the Gordon and Betty Moore Foundation, the Agouron Institute and the HHMI. \n\nAuthor Contributions: A.L., G.J.L., A.F., S.P.N. and M.G.S. conceived the manuscript layout and coordinated its writing. A.L., G.J.L., A.F., S.P.N., A.L.-G., D. Maresca, D. Malounda, R.W.B. and M.G.S developed methods for GV production, functionalization, and characterization, as well as for ultrasound imaging. M.Y., J.Y. and F.S.F. contributed methods for in vivo ultrasound imaging of GVs. M.K., C.W., L.S. and M.G.S. contributed methods for hyperpolarized xenon MRI of GVs. All authors contributed to writing the manuscript. A.L. compiled and edited the protocol and G.J.L. assembled the figures. \n\nThe authors declare no competing financial interests.\n\nAccepted Version - nihms-978825.pdf
Supplemental Material - nprot.2017.081-S1.pdf
Supplemental Material - nprot.2017.081-S2.zip
Supplemental Material - nprot.2017.081-SF1.jpg
", "abstract": "Gas vesicles (GVs) are a unique class of gas-filled protein nanostructures that are detectable at subnanomolar concentrations and whose physical properties allow them to serve as highly sensitive imaging agents for ultrasound and MRI. Here we provide a protocol for isolating GVs from native and heterologous host organisms, functionalizing these nanostructures with moieties for targeting and fluorescence, characterizing their biophysical properties and imaging them using ultrasound and MRI. GVs can be isolated from natural cyanobacterial and haloarchaeal host organisms or from Escherichia coli expressing a heterologous GV gene cluster and purified using buoyancy-assisted techniques. They can then be modified by replacing surface-bound proteins with engineered, heterologously expressed variants or through chemical conjugation, resulting in altered mechanical, surface and targeting properties. Pressurized absorbance spectroscopy is used to characterize their mechanical properties, whereas dynamic light scattering (DLS)and transmission electron microscopy (TEM) are used to determine nanoparticle size and morphology, respectively. GVs can then be imaged with ultrasound in vitro and in vivo using pulse sequences optimized for their detection versus background. They can also be imaged with hyperpolarized xenon MRI using chemical exchange saturation transfer between GV-bound and dissolved xenon\u2014a technique currently implemented in vitro. Taking 3\u20138 d to prepare, these genetically encodable nanostructures enable multimodal, noninvasive biological imaging with high sensitivity and potential for molecular targeting.", "date": "2017-10", "date_type": "published", "publication": "Nature Protocols", "volume": "12", "number": "10", "publisher": "Nature Publishing Group", "pagerange": "2050-2080", "id_number": "CaltechAUTHORS:20170517-151452626", "issn": "1754-2189", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170517-151452626", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01-EB018975" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "W911NF-14-1-0111" }, { "agency": "Canadian Institutes of Health Research (CIHR)", "grant_number": "FDN148367" }, { "agency": "Human Frontier Science Program", "grant_number": "RGP0050/2016" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1144469" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" }, { "agency": "Caltech Summer Undergraduate Research Fellowship (SURF)" }, { "agency": "Heritage Medical Research Institute" }, { "agency": "Burroughs Wellcome Fund" }, { "agency": "Pew Charitable Trust" }, { "agency": "Sontag Foundation" }, { "agency": "David and Lucile Packard Foundation" }, { "agency": "Michael J. Fox Foundation", "grant_number": "12549" }, { "agency": "Deutsche Forschungsgemeinschaft (DFG)", "grant_number": "SCHR 995/5-1" }, { "agency": "Arnold and Mabel Beckman Foundation" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Agouron Institute" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "local_group": { "items": [ { "id": "Heritage-Medical-Research-Institute" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1038/nprot.2017.081", "pmcid": "PMC6185898", "primary_object": { "basename": "nihms-978825.pdf", "url": "https://authors.library.caltech.edu/records/79ffp-qyg97/files/nihms-978825.pdf" }, "related_objects": [ { "basename": "nprot.2017.081-S1.pdf", "url": "https://authors.library.caltech.edu/records/79ffp-qyg97/files/nprot.2017.081-S1.pdf" }, { "basename": "nprot.2017.081-S2.zip", "url": "https://authors.library.caltech.edu/records/79ffp-qyg97/files/nprot.2017.081-S2.zip" }, { "basename": "nprot.2017.081-SF1.jpg", "url": "https://authors.library.caltech.edu/records/79ffp-qyg97/files/nprot.2017.081-SF1.jpg" } ], "pub_year": "2017", "author_list": "Lakshmanan, Anupama; Lu, George J.; et el." }, { "id": "https://authors.library.caltech.edu/records/rmknk-t3d80", "eprint_id": 78649, "eprint_status": "archive", "datestamp": "2023-08-21 21:49:50", "lastmod": "2023-10-26 00:15:46", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Hammer-S-C", "name": { "family": "Hammer", "given": "Stephan C." }, "orcid": "0000-0002-3620-9362" }, { "id": "Knight-A-M", "name": { "family": "Knight", "given": "Anders M." }, "orcid": "0000-0001-9665-8197" }, { "id": "Arnold-F-H", "name": { "family": "Arnold", "given": "Frances H." }, "orcid": "0000-0002-4027-364X" } ] }, "title": "Design and Evolution of Enzymes for Non-natural Chemistry", "ispublished": "pub", "full_text_status": "public", "keywords": "Biocatalysis; Directed Evolution; Sustainable Chemistry; Synthetic Biology; Protein Engineering", "note": "\u00a9 2017 Elsevier B.V. \n\nReceived 27 April 2017, Revised 22 May 2017, Accepted 7 June 2017, Available online 10 June 2017.", "abstract": "Enzymes are used in biocatalytic processes for the efficient and sustainable production of pharmaceuticals, fragrances, fine chemicals, and other products. Most bioprocesses exploit chemistry found in nature, but we are now entering a realm of biocatalysis that goes well beyond. Enzymes have been engineered to catalyze reactions previously only accessible with synthetic catalysts. Because they can be tuned by directed evolution, many of these new biocatalysts have been shown to perform abiological reactions with high activity and selectivity. We discuss recent examples, showcase catalyst improvements achieved using directed evolution, and comment on some current and future implications of non-natural enzyme evolution for sustainable chemical synthesis.", "date": "2017-10", "date_type": "published", "publication": "Current Opinion in Green and Sustainable Chemistry", "volume": "7", "publisher": "Elsevier", "pagerange": "23-30", "id_number": "CaltechAUTHORS:20170628-110616752", "issn": "2452-2236", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170628-110616752", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1016/j.cogsc.2017.06.002", "pub_year": "2017", "author_list": "Hammer, Stephan C.; Knight, Anders M.; et el." }, { "id": "https://authors.library.caltech.edu/records/mpg16-qvr61", "eprint_id": 79281, "eprint_status": "archive", "datestamp": "2023-08-19 04:12:42", "lastmod": "2023-10-26 14:45:48", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Glasser-Nathaniel-R", "name": { "family": "Glasser", "given": "Nathaniel R." }, "orcid": "0000-0002-2833-5166" }, { "id": "Saunders-Scott-H", "name": { "family": "Saunders", "given": "Scott H." }, "orcid": "0000-0003-4224-9106" }, { "id": "Newman-D-K", "name": { "family": "Newman", "given": "Dianne K." }, "orcid": "0000-0003-1647-1918" } ] }, "title": "The Colorful World of Extracellular Electron Shuttles", "ispublished": "pub", "full_text_status": "public", "keywords": "extracellular electron shuttle, metabolism, microbial diversity, public goods, redox chemistry", "note": "\u00a9 2017 Annual Reviews. \n\nReview in Advance first posted online on July 21, 2017. \n\nWe thank Leonard Tender, Matthew Yates, and members of the Newman lab for helpful comments on the manuscript; Muir Morrison, Tal Einav, and Manuel Razo for guidance in deriving the three-dimensional diffusion model; and Tomislav Ivankovic for allowing us to use his memorable microbial artwork in Figure 1. Financial support from the Donna and Benjamin M. Rosen Bioengineering Center, NIH (1R01AI127850-01A1), and ARO (W911NF-17-1-0024) enabled this work.\n\nDisclosure Statement: The authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this review.\n\nAccepted Version - nihms914123.pdf
", "abstract": "Descriptions of the changeable, striking colors associated with secreted natural products date back well over a century. These molecules can serve as extracellular electron shuttles (EESs) that permit microbes to access substrates at a distance. In this review, we argue that the colorful world of EESs has been too long neglected. Rather than simply serving as a diagnostic attribute of a particular microbial strain, redox-active natural products likely play fundamental, underappreciated roles in the biology of their producers, particularly those that inhabit biofilms. Here, we describe the chemical diversity and potential distribution of EES producers and users, discuss the costs associated with their biosynthesis, and critically evaluate strategies for their economical usage. We hope this review will inspire efforts to identify and explore the importance of EES cycling by a wide range of microorganisms so that their contributions to shaping microbial communities can be better assessed and exploited.", "date": "2017-07-24", "date_type": "published", "publication": "Annual Review of Microbiology", "volume": "71", "publisher": "Annual Reviews", "pagerange": "731-751", "id_number": "CaltechAUTHORS:20170724-072743727", "issn": "0066-4227", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170724-072743727", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH", "grant_number": "1R01AI127850-01A1" }, { "agency": "Army Research Office (ARO)", "grant_number": "W911NF-17-1-0024" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" }, { "id": "Division-of-Geological-and-Planetary-Sciences" } ] }, "doi": "10.1146/annurev-micro-090816-093913", "pmcid": "PMC5679407", "primary_object": { "basename": "nihms914123.pdf", "url": "https://authors.library.caltech.edu/records/mpg16-qvr61/files/nihms914123.pdf" }, "pub_year": "2017", "author_list": "Glasser, Nathaniel R.; Saunders, Scott H.; et el." }, { "id": "https://authors.library.caltech.edu/records/sb7x9-22d61", "eprint_id": 76551, "eprint_status": "archive", "datestamp": "2023-08-19 03:48:28", "lastmod": "2023-10-25 16:06:21", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Prier-Christopher-K", "name": { "family": "Prier", "given": "Christopher K." }, "orcid": "0000-0003-0902-1636" }, { "id": "Zhang-Ruijie-K", "name": { "family": "Zhang", "given": "Ruijie K." }, "orcid": "0000-0002-7251-5527" }, { "id": "Buller-Andrew-R", "name": { "family": "Buller", "given": "Andrew R." }, "orcid": "0000-0002-9635-4844" }, { "id": "Brinkmann-Chen-Sabine", "name": { "family": "Brinkmann-Chen", "given": "Sabine" }, "orcid": "0000-0002-5419-4192" }, { "id": "Arnold-F-H", "name": { "family": "Arnold", "given": "Frances H." }, "orcid": "0000-0002-4027-364X" } ] }, "title": "Enantioselective, intermolecular benzylic C\u2013H amination catalysed by an engineered iron-haem enzyme", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2017 Macmillan Publishers Limited. \n\nReceived 14 March 2017. Accepted 21 April 2017. Published online 29 May 2017. \n\nOur research is supported by the National Science Foundation, Division of Molecular and Cellular Biosciences (grant MCB-1513007) and by funds from the American Recovery and Reinvestment Act (ARRA) through the National Institutes of Health Shared Instrumentation Grant Program (S10RR027203). C.K.P. thanks the Resnick Sustainability Institute for a postdoctoral fellowship. R.K.Z. was supported by a National Science Foundation Graduate Research Fellowship (NSF GRFP; DGE-1144469), is a trainee in the Caltech Biotechnology Leadership Program, and has received financial support from the Donna and Benjamin M. Rosen Bioengineering Center. A.R.B. is funded by a Ruth Kirschstein NIH Postdoctoral Fellowship F32G110851. We thank S.\u2009Virgil, J.\u2009Kaiser, and R.\u2009D. Lewis for experimental assistance, and O.\u2009F. Brandenberg, S.\u2009C. Hammer, and S.\u2009B.\u2009J.\u2009Kan for helpful discussion and comments on the manuscript. \n\nThese authors contributed equally to this work. Christopher K. Prier & Ruijie K. Zhang. \n\nAuthor ontributions: C.K.P. and R.K.Z. designed, carried out, and analysed all amination experiments, with F.H.A. providing guidance. C.K.P., R.K.Z. and S.B.-C. obtained protein crystals. R.K.Z. and A.R.B. solved the crystal structure. C.K.P. and F.H.A. wrote the manuscript with input from all of the authors. \n\nData availability: Complete experimental procedures, including synthesis methods for all compounds, characterization data, and details of bioconversion experiments are described in the Supplementary Information. The crystal structure of P411_(BM3) P-4 A82L A78V F263L has been deposited in the Protein Data Bank (PDB) under accession code 5UCW. \n\nThe authors declare no competing financial interests.\n\nAccepted Version - nihms886928.pdf
Supplemental Material - nchem.2783-s1.pdf
", "abstract": "C\u2013H bonds are ubiquitous structural units of organic molecules. Although these bonds are generally considered to be chemically inert, the recent emergence of methods for C\u2013H functionalization promises to transform the way synthetic chemistry is performed. The intermolecular amination of C\u2013H bonds represents a particularly desirable and challenging transformation for which no efficient, highly selective, and renewable catalysts exist. Here we report the directed evolution of an iron-containing enzymatic catalyst\u2014based on a cytochrome P450 monooxygenase\u2014for the highly enantioselective intermolecular amination of benzylic C\u2013H bonds. The biocatalyst is capable of up to 1,300 turnovers, exhibits excellent enantioselectivities, and provides access to valuable benzylic amines. Iron complexes are generally poor catalysts for C\u2013H amination: in this catalyst, the enzyme's protein framework confers activity on an otherwise unreactive iron-haem cofactor.", "date": "2017-07", "date_type": "published", "publication": "Nature Chemistry", "volume": "9", "number": "7", "publisher": "Nature Publishing Group", "pagerange": "629-634", "id_number": "CaltechAUTHORS:20170413-120718900", "issn": "1755-4330", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170413-120718900", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NSF", "grant_number": "MCB-1513007" }, { "agency": "American Recovery and Reinvestment Act (ARRA)" }, { "agency": "NIH", "grant_number": "S10RR027203" }, { "agency": "Resnick Sustainability Institute" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1144469" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "F32G110851" } ] }, "local_group": { "items": [ { "id": "Resnick-Sustainability-Institute" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1038/nchem.2783", "pmcid": "PMC5555633", "primary_object": { "basename": "nchem.2783-s1.pdf", "url": "https://authors.library.caltech.edu/records/sb7x9-22d61/files/nchem.2783-s1.pdf" }, "related_objects": [ { "basename": "nihms886928.pdf", "url": "https://authors.library.caltech.edu/records/sb7x9-22d61/files/nihms886928.pdf" } ], "pub_year": "2017", "author_list": "Prier, Christopher K.; Zhang, Ruijie K.; et el." }, { "id": "https://authors.library.caltech.edu/records/239ws-b2z58", "eprint_id": 75032, "eprint_status": "archive", "datestamp": "2023-08-19 02:11:55", "lastmod": "2023-10-25 14:41:04", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Bedbrook-Claire-N", "name": { "family": "Bedbrook", "given": "Claire N." }, "orcid": "0000-0003-3973-598X" }, { "id": "Rice-Austin-J", "name": { "family": "Rice", "given": "Austin J." } }, { "id": "Yang-Kevin-K", "name": { "family": "Yang", "given": "Kevin K." }, "orcid": "0000-0001-9045-6826" }, { "id": "Ding-Xiaozhe-Z", "name": { "family": "Ding", "given": "Xiaozhe" }, "orcid": "0000-0002-0267-0791" }, { "id": "Chen-Siyuan", "name": { "family": "Chen", "given": "Siyuan" } }, { "id": "Le-Proust-Emily-M", "name": { "family": "LeProust", "given": "Emily M." } }, { "id": "Gradinaru-V", "name": { "family": "Gradinaru", "given": "Viviana" }, "orcid": "0000-0001-5868-348X" }, { "id": "Arnold-F-H", "name": { "family": "Arnold", "given": "Frances H." }, "orcid": "0000-0002-4027-364X" } ] }, "title": "Structure-guided SCHEMA recombination generates diverse chimeric channelrhodopsins", "ispublished": "pub", "full_text_status": "public", "keywords": "membrane proteins | channelrhodopsin | structure-guided recombination | chimeragenesis", "note": "\u00a9 2017 National Academy of Sciences. \n\nContributed by Frances H. Arnold, February 13, 2017 (sent for review January 6, 2017; reviewed by Hagan Bayley and David Drew) Published online before print March 10, 2017. \n\nWe thank Dr. John Bedbrook for critical reading of the manuscript. Imaging was performed in the Biological Imaging Facility, with the support of the Caltech Beckman Institute and the Arnold and Mabel Beckman Foundation. This work is funded by the National Institute for Mental Health Grant R21MH103824 (to V.G. and F.H.A.); the Beckman Institute for CLARITY, Optogenetics and Vector Engineering Research for technology development and broad dissemination: www.beckmaninstitute.caltech.edu/clover.shtml (V.G.); and the Institute for Collaborative Biotechnologies through Grant W911F-09-0001 from the US Army Research Office (to F.H.A.). C.N.B. and A.J.R. are funded by Ruth L. Kirschstein National Research Service Awards F31MH102913 and F32GM116319. K.K.Y. is a trainee in the Caltech Biotechnology Leadership Program and has received financial support from the Donna and Benjamin M. Rosen Bioengineering Center. The content is solely the responsibility of the authors and does not necessarily reflect the position or policy of the National Center for Research Resources, the National Institutes of Health, or the Government, and no official endorsement should be inferred. \n\nC.N.B. and A.J.R. contributed equally to this work. \n\nAuthor contributions: C.N.B., A.J.R., V.G., and F.H.A. designed research; C.N.B., A.J.R., and X.D. performed research; S.C. and E.M.L. contributed synthesized ChR genes; C.N.B. and A.J.R. analyzed data; and C.N.B., A.J.R., K.K.Y., and F.H.A. wrote the paper. \n\nReviewers: H.B., University of Oxford; and D.D., Stockholm University. \n\nThe authors declare no conflict of interest. \n\nThis article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1700269114/-/DCSupplemental.\n\nPublished - PNAS-2017-Bedbrook-E2624-33.pdf
Supplemental Material - pnas.1700269114.sd01.csv
Supplemental Material - pnas.1700269114.sd02.csv
Supplemental Material - pnas.1700269114.sd03.txt
Supplemental Material - pnas.1700269114.sd04.txt
Supplemental Material - pnas.1700269114.sd05.txt
Supplemental Material - pnas.201700269SI.pdf
", "abstract": "Integral membrane proteins (MPs) are key engineering targets due to their critical roles in regulating cell function. In engineering MPs, it can be extremely challenging to retain membrane localization capability while changing other desired properties. We have used structure-guided SCHEMA recombination to create a large set of functionally diverse chimeras from three sequence-diverse channelrhodopsins (ChRs). We chose 218 ChR chimeras from two SCHEMA libraries and assayed them for expression and plasma membrane localization in human embryonic kidney cells. The majority of the chimeras express, with 89% of the tested chimeras outperforming the lowest-expressing parent; 12% of the tested chimeras express at even higher levels than any of the parents. A significant fraction (23%) also localize to the membrane better than the lowest-performing parent ChR. Most (93%) of these well-localizing chimeras are also functional light-gated channels. Many chimeras have stronger light-activated inward currents than the three parents, and some have unique off-kinetics and spectral properties relative to the parents. An effective method for generating protein sequence and functional diversity, SCHEMA recombination can be used to gain insights into sequence\u2013function relationships in MPs.", "date": "2017-03-28", "date_type": "published", "publication": "Proceedings of the National Academy of Sciences of the United States of America", "volume": "114", "number": "13", "publisher": "National Academy of Sciences", "pagerange": "E2624-E2633", "id_number": "CaltechAUTHORS:20170310-130542741", "issn": "0027-8424", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170310-130542741", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Caltech Beckman Institute" }, { "agency": "Arnold and Mabel Beckman Foundation" }, { "agency": "NIH", "grant_number": "R21MH103824" }, { "agency": "Army Research Office (ARO)", "grant_number": "W911F-09-0001" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "F31MH102913" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "F32GM116319" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" } ] }, "local_group": { "items": [ { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1073/pnas.1700269114", "pmcid": "PMC5380088", "primary_object": { "basename": "pnas.1700269114.sd04.txt", "url": "https://authors.library.caltech.edu/records/239ws-b2z58/files/pnas.1700269114.sd04.txt" }, "related_objects": [ { "basename": "pnas.1700269114.sd05.txt", "url": "https://authors.library.caltech.edu/records/239ws-b2z58/files/pnas.1700269114.sd05.txt" }, { "basename": "pnas.201700269SI.pdf", "url": "https://authors.library.caltech.edu/records/239ws-b2z58/files/pnas.201700269SI.pdf" }, { "basename": "PNAS-2017-Bedbrook-E2624-33.pdf", "url": "https://authors.library.caltech.edu/records/239ws-b2z58/files/PNAS-2017-Bedbrook-E2624-33.pdf" }, { "basename": "pnas.1700269114.sd01.csv", "url": "https://authors.library.caltech.edu/records/239ws-b2z58/files/pnas.1700269114.sd01.csv" }, { "basename": "pnas.1700269114.sd02.csv", "url": "https://authors.library.caltech.edu/records/239ws-b2z58/files/pnas.1700269114.sd02.csv" }, { "basename": "pnas.1700269114.sd03.txt", "url": "https://authors.library.caltech.edu/records/239ws-b2z58/files/pnas.1700269114.sd03.txt" } ], "pub_year": "2017", "author_list": "Bedbrook, Claire N.; Rice, Austin J.; et el." }, { "id": "https://authors.library.caltech.edu/records/eyt49-dzw75", "eprint_id": 74829, "eprint_status": "archive", "datestamp": "2023-08-22 19:53:37", "lastmod": "2023-10-24 23:20:37", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Herwig-Lukas", "name": { "family": "Herwig", "given": "Lukas" } }, { "id": "Rice-Austin-J", "name": { "family": "Rice", "given": "Austin J." } }, { "id": "Bedbrook-Claire-N", "name": { "family": "Bedbrook", "given": "Claire N." }, "orcid": "0000-0003-3973-598X" }, { "id": "Zhang-Ruijie-K", "name": { "family": "Zhang", "given": "Ruijie K." }, "orcid": "0000-0002-7251-5527" }, { "id": "Lignell-Antti", "name": { "family": "Lignell", "given": "Antti" }, "orcid": "0000-0001-7664-5583" }, { "id": "Cahn-Jackson-K-B", "name": { "family": "Cahn", "given": "Jackson K. B." } }, { "id": "Renata-Hans", "name": { "family": "Renata", "given": "Hans" }, "orcid": "0000-0003-2468-2328" }, { "id": "Dodani-Sheel-C", "name": { "family": "Dodani", "given": "Sheel C." } }, { "id": "Cho-Inha", "name": { "family": "Cho", "given": "Inha" }, "orcid": "0000-0002-7564-5378" }, { "id": "Cai-Long", "name": { "family": "Cai", "given": "Long" }, "orcid": "0000-0002-7154-5361" }, { "id": "Gradinaru-V", "name": { "family": "Gradinaru", "given": "Viviana" }, "orcid": "0000-0001-5868-348X" }, { "id": "Arnold-F-H", "name": { "family": "Arnold", "given": "Frances H." }, "orcid": "0000-0002-4027-364X" } ] }, "title": "Directed Evolution of a Bright Near-Infrared Fluorescent Rhodopsin Using a Synthetic Chromophore", "ispublished": "pub", "full_text_status": "public", "keywords": "synthetic chromophore substitution; directed evolution; protein engineering; near-infrared fluorescence; Archaerhodopsin; live-cell imaging", "note": "\u00a9 2017 Elsevier Ltd. \n\nReceived 1 July 2016, Revised 28 November 2016, Accepted 1 February 2017, Available online 2 March 2017. Published: March 2, 2017. \n\nThe authors would like to thank Sabine Brinkmann-Chen and Andrew Buller for critical review of the manuscript and David VanderVelde for assistance with NMR analysis. L.H. was supported by a fellowship from the Swiss National Science Foundation (SNSF; P2BSP3_151863). The Ruth L. Kirschstein National Research Service Award supports A.J.R. (F32GM116319), C.N.B. (F31MH102913), and S.C.D. (5F32GM106618). R.K.Z. was supported by a National Science Foundation Graduate Research Fellowship (NSF GRFP; DGE-1144469), is a trainee in the Caltech Biotechnology Leadership Program, and has received financial support from the Donna and Benjamin M. Rosen Bioengineering Center. J.K.B.C. acknowledges the support of the Resnick Sustainability Institute (Caltech). Research is supported by the National Center for Research Resources, ARRA SIG Program S10RR027203 (F.H.A.); National Institute of Mental Health R21MH103824 (V.G. and F.H.A.); and the Institute for Collaborative Biotechnologies through grant number W911F-09-0001 from the US Army Research Office (F.H.A.). The authors would like to acknowledge the Beckman Institute for the Resource Center on CLARITY, Optogenetics, and Vector Engineering for technology development and broad dissemination (http://www.beckmaninstitute.caltech.edu/clover.shtml). The content is solely the responsibility of the authors and does not necessarily reflect the position or policy of the National Center for Research Resources, the NIH, or the Government, and no official endorsement should be inferred.\n\nAccepted Version - nihms850709.pdf
Supplemental Material - mmc1.pdf
Supplemental Material - mmc2.zip
", "abstract": "By engineering a microbial rhodopsin, Archaerhodopsin-3 (Arch), to bind a synthetic chromophore, merocyanine retinal, in place of the natural chromophore all-trans-retinal (ATR), we generated a protein with exceptionally bright and unprecedentedly red-shifted near-infrared (NIR) fluorescence. We show that chromophore substitution generates a fluorescent Arch complex with a 200-nm bathochromic excitation shift relative to ATR-bound wild-type Arch and an emission maximum at 772 nm. Directed evolution of this complex produced variants with pH-sensitive NIR fluorescence and molecular brightness 8.5-fold greater than the brightest ATR-bound Arch variant. The resulting proteins are well suited to bacterial imaging; expression and stability have not been optimized for mammalian cell imaging. By targeting both the protein and its chromophore, we overcome inherent challenges associated with engineering bright NIR fluorescence into Archaerhodopsin. This work demonstrates an efficient strategy for engineering non-natural, tailored properties into microbial opsins, properties relevant for imaging and interrogating biological systems.", "date": "2017-03-16", "date_type": "published", "publication": "Cell Chemical Biology", "volume": "24", "number": "3", "publisher": "Cell Press", "pagerange": "415-425", "id_number": "CaltechAUTHORS:20170307-082231020", "issn": "2451-9456", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20170307-082231020", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Swiss National Science Foundation (SNSF)", "grant_number": "P2BSP3_151863" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "F32GM116319" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "F31MH102913" }, { "agency": "NIH", "grant_number": "5F32GM106618" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1144469" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "Resnick Sustainability Institute" }, { "agency": "NIH", "grant_number": "S10RR027203" }, { "agency": "NIH", "grant_number": "R21MH103824" }, { "agency": "Army Research Office (ARO)", "grant_number": "W911F-09-0001" }, { "agency": "National Institute of Mental Health (NIMH)" } ] }, "local_group": { "items": [ { "id": "Resnick-Sustainability-Institute" }, { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1016/j.chembiol.2017.02.008", "pmcid": "PMC5357175", "primary_object": { "basename": "mmc1.pdf", "url": "https://authors.library.caltech.edu/records/eyt49-dzw75/files/mmc1.pdf" }, "related_objects": [ { "basename": "mmc2.zip", "url": "https://authors.library.caltech.edu/records/eyt49-dzw75/files/mmc2.zip" }, { "basename": "nihms850709.pdf", "url": "https://authors.library.caltech.edu/records/eyt49-dzw75/files/nihms850709.pdf" } ], "pub_year": "2017", "author_list": "Herwig, Lukas; Rice, Austin J.; et el." }, { "id": "https://authors.library.caltech.edu/records/zzsww-f2n17", "eprint_id": 70967, "eprint_status": "archive", "datestamp": "2023-08-20 14:01:55", "lastmod": "2023-10-23 15:15:43", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Zhou-Edward-Haojiang", "name": { "family": "Zhou", "given": "Edward Haojiang" }, "orcid": "0000-0001-7020-9502" }, { "id": "Shibukawa-Atsushi", "name": { "family": "Shibukawa", "given": "Atsushi" } }, { "id": "Brake-Joshua-H", "name": { "family": "Brake", "given": "Joshua" }, "orcid": "0000-0002-5113-6886" }, { "id": "Ruan-Haowen", "name": { "family": "Ruan", "given": "Haowen" }, "orcid": "0000-0002-4917-4509" }, { "id": "Yang-Changhuei", "name": { "family": "Yang", "given": "Changhuei" }, "orcid": "0000-0001-8791-0354" } ] }, "title": "Glare suppression by coherence gated negation", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2016 Optical Society of America. \n\nReceived 11 July 2016; revised 6 September 2016; accepted 9 September 2016 (Doc. ID 270225); published 5 October 2016. \n\nAcknowledgment. The authors thank Dr. Mooseok Jang and Ms. Michelle Cua for helpful discussions. J. B. acknowledges support from the National Institute of Biomedical Imaging and Bioengineering under a Ruth L. Kirschstein National Research Service Award and from the Donna and Benjamin M. Rosen Bioengineering Center. \n\nFunding. National Institutes of Health (NIH)(1U01NS090577-01); GIST-Caltech Collaborative Research Proposal (CG2016). National Institute of Biomedical Imaging and Bioengineering (NIBIB) (1F31EB021153-01); Donna and Benjamin M. Rosen Bioengineering Center.\n\nPublished - optica-3-10-1107.pdf
Accepted Version - nihms835229.pdf
Submitted - 1606.04570.pdf
Supplemental Material - 1107.AVI
Supplemental Material - optica-3-10-1107-supp1.pdf
", "abstract": "Imaging of a weak target hidden behind a scattering medium can be significantly confounded by glare. We report a method, termed coherence gated negation (CGN), that uses destructive optical interference to suppress glare and allow improved imaging of a weak target. As a demonstration, we show that by permuting through a set range of amplitude and phase values for a reference beam interfering with the optical field from the glare and target reflection, we can suppress glare by an order of magnitude, even when the optical wavefront is highly disordered. This strategy significantly departs from conventional coherence gating methods in that CGN actively \"gates out\" the unwanted optical contributions while conventional methods \"gate in\" the target optical signal. We further show that the CGN method can outperform conventional coherence gating image quality in certain scenarios by more effectively rejecting unwanted optical contributions.", "date": "2016-10", "date_type": "published", "publication": "Optica", "volume": "3", "number": "10", "publisher": "Optical Society of America", "pagerange": "1107-1113", "id_number": "CaltechAUTHORS:20161010-124426959", "issn": "2334-2536", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20161010-124426959", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "1U01NS090577-01" }, { "agency": "GIST-Caltech Research Collaboration", "grant_number": "CG2016" }, { "agency": "NIH Postdoctoral Fellowship", "grant_number": "1F31EB021153-01" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH Predoctoral Fellowship" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1364/OPTICA.3.001107", "pmcid": "PMC5509221", "primary_object": { "basename": "optica-3-10-1107.pdf", "url": "https://authors.library.caltech.edu/records/zzsww-f2n17/files/optica-3-10-1107.pdf" }, "related_objects": [ { "basename": "1107.AVI", "url": "https://authors.library.caltech.edu/records/zzsww-f2n17/files/1107.AVI" }, { "basename": "1606.04570.pdf", "url": "https://authors.library.caltech.edu/records/zzsww-f2n17/files/1606.04570.pdf" }, { "basename": "nihms835229.pdf", "url": "https://authors.library.caltech.edu/records/zzsww-f2n17/files/nihms835229.pdf" }, { "basename": "optica-3-10-1107-supp1.pdf", "url": "https://authors.library.caltech.edu/records/zzsww-f2n17/files/optica-3-10-1107-supp1.pdf" } ], "pub_year": "2016", "author_list": "Zhou, Edward Haojiang; Shibukawa, Atsushi; et el." }, { "id": "https://authors.library.caltech.edu/records/cw7hv-0xq40", "eprint_id": 69033, "eprint_status": "archive", "datestamp": "2023-08-20 13:28:40", "lastmod": "2023-10-20 16:27:41", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lakshmanan-Anupama", "name": { "family": "Lakshmanan", "given": "Anupama" }, "orcid": "0000-0002-6702-837X" }, { "id": "Farhadi-Arash", "name": { "family": "Farhadi", "given": "Arash" }, "orcid": "0000-0001-9137-8559" }, { "id": "Nety-Suchita-P", "name": { "family": "Nety", "given": "Suchita P." }, "orcid": "0000-0002-4201-1061" }, { "id": "Lee-Gosselin-Audrey", "name": { "family": "Lee-Gosselin", "given": "Audrey" }, "orcid": "0000-0002-2431-2741" }, { "id": "Bourdeau-Raymond-W", "name": { "family": "Bourdeau", "given": "Raymond W." }, "orcid": "0000-0003-2202-1980" }, { "id": "Maresca-David", "name": { "family": "Maresca", "given": "David" }, "orcid": "0000-0002-4921-6406" }, { "id": "Shapiro-M-G", "name": { "family": "Shapiro", "given": "Mikhail G." }, "orcid": "0000-0002-0291-4215" } ] }, "title": "Molecular Engineering of Acoustic Protein Nanostructures", "ispublished": "pub", "full_text_status": "public", "keywords": "acoustic nanostructures, ultrasound, gas vesicles, protein engineering, genetic engineering, molecular imaging, contrast agents, cancer, macrophages", "note": "\u00a9 2016 American Chemical Society. \n\nReceived: May 21, 2016; Accepted: June 28, 2016. Publication Date (Web): June 28, 2016. \n\nThe authors thank Jordan Dykes and Nikita Reznik for assistance with experimental apparatus and Assaf Gilad for sharing the LRP gene. The authors also thank Alasdair McDowall for assistance with TEM. This research was supported by the NIH (EB018975) and DARPA (W911NF-14-1-0111). A.L. is supported by the NSF graduate research fellowship (award number 1144469). A.F. is supported by the NSERC graduate fellowship. D.M. is supported by the Human Frontiers Science Program Cross-Disciplinary Postdoctoral Fellowship. Research in the Shapiro laboratory is also supported by the Heritage Medical Research Institute and the Burroughs Wellcome Career Award at the Scientific Interface. \n\nAuthor Contributions: M.G.S. and A.L. conceived the study. A.L., A.F., and S.P.N. designed and planned experiments. A.L., A.F., S.P.N., A.L-G., and D.M. conducted the experiments and analyzed data. R.W.B., A.L., D.M., and M.G.S. wrote the MATLAB scripts for ultrasound imaging and data processing. A.L. and M.G.S. wrote the manuscript with input from all authors. \n\nThe authors declare no competing financial interest.\n\nAccepted Version - nihms978828.pdf
Supplemental Material - nn6b03364_si_001.pdf
", "abstract": "Ultrasound is among the most widely used biomedical imaging modalities, but has limited ability to image specific molecular targets due to the lack of suitable nanoscale contrast agents. Gas vesicles\u2014genetically encoded protein nanostructures isolated from buoyant photosynthetic microbes\u2014have recently been identified as nanoscale reporters for ultrasound. Their unique physical properties give gas vesicles significant advantages over conventional microbubble contrast agents, including nanoscale dimensions and inherent physical stability. Furthermore, as a genetically encoded material, gas vesicles present the possibility that the nanoscale mechanical, acoustic, and targeting properties of an imaging agent can be engineered at the level of its constituent proteins. Here, we demonstrate that genetic engineering of gas vesicles results in nanostructures with new mechanical, acoustic, surface, and functional properties to enable harmonic, multiplexed, and multimodal ultrasound imaging as well as cell-specific molecular targeting. These results establish a biomolecular platform for the engineering of acoustic nanomaterials.", "date": "2016-08-23", "date_type": "published", "publication": "ACS Nano", "volume": "10", "number": "8", "publisher": "American Chemical Society", "pagerange": "7314-7322", "id_number": "CaltechAUTHORS:20160714-134344625", "issn": "1936-0851", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160714-134344625", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "EB018975" }, { "agency": "Defense Advanced Research Projects Agency (DARPA)", "grant_number": "W911NF-14-1-0111" }, { "agency": "NSF Graduate Research Fellowship", "grant_number": "DGE-1144469" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" }, { "agency": "Human Frontier Science Program" }, { "agency": "Heritage Medical Research Institute" }, { "agency": "Burroughs Wellcome Fund" } ] }, "local_group": { "items": [ { "id": "Heritage-Medical-Research-Institute" }, { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1021/acsnano.6b03364", "pmcid": "PMC6058967", "primary_object": { "basename": "nihms978828.pdf", "url": "https://authors.library.caltech.edu/records/cw7hv-0xq40/files/nihms978828.pdf" }, "related_objects": [ { "basename": "nn6b03364_si_001.pdf", "url": "https://authors.library.caltech.edu/records/cw7hv-0xq40/files/nn6b03364_si_001.pdf" } ], "pub_year": "2016", "author_list": "Lakshmanan, Anupama; Farhadi, Arash; et el." }, { "id": "https://authors.library.caltech.edu/records/6aj9f-1fn46", "eprint_id": 65873, "eprint_status": "archive", "datestamp": "2023-08-20 11:13:27", "lastmod": "2023-10-18 16:53:01", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Mahdavi-Alborz", "name": { "family": "Mahdavi", "given": "Alborz" }, "orcid": "0000-0002-8790-8112" }, { "id": "Hamblin-Graham-D", "name": { "family": "Hamblin", "given": "Graham D." } }, { "id": "Jindal-Granton-A", "name": { "family": "Jindal", "given": "Granton A." }, "orcid": "0000-0003-2803-9831" }, { "id": "Bagert-John-D", "name": { "family": "Bagert", "given": "John D." }, "orcid": "0000-0001-7768-2853" }, { "id": "Dong-Cathy", "name": { "family": "Dong", "given": "Cathy" } }, { "id": "Sweredoski-Michael-J", "name": { "family": "Sweredoski", "given": "Michael J." }, "orcid": "0000-0003-0878-3831" }, { "id": "Hess-Sonja", "name": { "family": "Hess", "given": "Sonja" }, "orcid": "0000-0002-5904-9816" }, { "id": "Schuman-E-M", "name": { "family": "Schuman", "given": "Erin M." }, "orcid": "0000-0002-7053-1005" }, { "id": "Tirrell-D-A", "name": { "family": "Tirrell", "given": "David A." }, "orcid": "0000-0003-3175-4596" } ] }, "title": "Engineered Aminoacyl-tRNA Synthetase for Cell-Selective Analysis of Mammalian Protein Synthesis", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2016 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. \n\nReceived: August 24, 2015. Publication Date (Web): March 18, 2016. \n\nWe are grateful for financial support by National Institutes of Health grant NIH R01 GM062523 and the Programmable Molecular Technology Initiative of the Gordon and Betty Moore Foundation, the Institute for Collaborative Biotechnologies through grant W911NF-09-0001 from U.S. Army Research Office. M.S. and S.H. were supported by the Gordon and Betty Moore Foundation through grant GMBF775 and NIH grant 1S10RR029594-01A1. A.M. was supported by a scholarship from the National Science and Engineering Research Council of Canada and by a postgraduate scholarship from the Donna and Benjamin M. Rosen Center for Bioengineering at Caltech. G.D.H. was supported by a postdoctoral fellowship from the National Science and Engineering Research Council of Canada. \n\nThe authors declare no competing financial interest.\n\nPublished - ja5b08980.pdf
Supplemental Material - ja5b08980_si_001.pdf
Supplemental Material - ja5b08980_si_002.xlsx
Supplemental Material - ja5b08980_si_003.xlsx
", "abstract": "Methods for cell-selective analysis of proteome dynamics will facilitate studies of biological processes in multicellular organisms. Here we describe a mutant murine methionyl-tRNA synthetase (designated L274GMmMetRS) that charges the noncanonical amino acid azidonorleucine (Anl) to elongator tRNA^(Met) in hamster (CHO), monkey (COS7), and human (HeLa) cell lines. Proteins made in cells that express the synthetase can be labeled with Anl, tagged with dyes or affinity reagents, and enriched on affinity resin to facilitate identification by mass spectrometry. The method does not require expression of orthogonal tRNAs or depletion of canonical amino acids. Successful labeling of proteins with Anl in several mammalian cell lines demonstrates the utility of L274GMmMetRS as a tool for cell-selective analysis of mammalian protein synthesis.", "date": "2016-04-06", "date_type": "published", "publication": "Journal of the American Chemical Society", "volume": "138", "number": "13", "publisher": "American Chemical Society", "pagerange": "4278-4281", "id_number": "CaltechAUTHORS:20160404-075529150", "issn": "0002-7863", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160404-075529150", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 GM062523" }, { "agency": "Gordon and Betty Moore Foundation" }, { "agency": "Army Research Office (ARO)", "grant_number": "W911NF-09-0001" }, { "agency": "Gordon and Betty Moore Foundation", "grant_number": "GMBF775" }, { "agency": "NIH", "grant_number": "1S10RR029594-01A1" }, { "agency": "Natural Sciences and Engineering Research Council of Canada (NSERC)" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1021/jacs.5b08980", "pmcid": "PMC4825725", "primary_object": { "basename": "ja5b08980.pdf", "url": "https://authors.library.caltech.edu/records/6aj9f-1fn46/files/ja5b08980.pdf" }, "related_objects": [ { "basename": "ja5b08980_si_001.pdf", "url": "https://authors.library.caltech.edu/records/6aj9f-1fn46/files/ja5b08980_si_001.pdf" }, { "basename": "ja5b08980_si_002.xlsx", "url": "https://authors.library.caltech.edu/records/6aj9f-1fn46/files/ja5b08980_si_002.xlsx" }, { "basename": "ja5b08980_si_003.xlsx", "url": "https://authors.library.caltech.edu/records/6aj9f-1fn46/files/ja5b08980_si_003.xlsx" } ], "pub_year": "2016", "author_list": "Mahdavi, Alborz; Hamblin, Graham D.; et el." }, { "id": "https://authors.library.caltech.edu/records/awp3m-dpp59", "eprint_id": 64563, "eprint_status": "archive", "datestamp": "2023-08-20 10:10:37", "lastmod": "2023-10-17 21:30:40", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Brake-Joshua-H", "name": { "family": "Brake", "given": "Joshua" }, "orcid": "0000-0002-5113-6886" }, { "id": "Jang-Mooseok", "name": { "family": "Jang", "given": "Mooseok" }, "orcid": "0000-0003-1977-9539" }, { "id": "Yang-Changhuei", "name": { "family": "Yang", "given": "Changhuei" }, "orcid": "0000-0001-8791-0354" } ] }, "title": "Analyzing the relationship between decorrelation time and tissue thickness in acute rat brain slices using multispeckle diffusing wave spectroscopy", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2016 Optical Society of America. \n\nReceived 6 October 2015; revised 4 December 2015; accepted 26 December 2015; posted 5 January 2016 (Doc. ID 251465); published 1 February 2016. \n\nFunding: National Institute of Biomedical Imaging and Bioengineering (NIBIB) (1F31EB021153-01); National Institute of Neurological Disorders and Stroke (NINDS) (1U01NS090577-01); National Institutes of Health (NIH) (1DP2OD007307-01); Donna and Benjamin M. Rosen Bioengineering Center; GIST-Caltech (CG2012). \n\nJ. B. acknowledges support from an NIH NRSA Predoctoral Fellowship and the Donna and Benjamin M. Rosen Bioengineering Center. The authors would also like to thank Dr. Cheng Xiao for his help in preparing the brain tissue slices.\n\nPublished - josaa-33-2-270.pdf
", "abstract": "Novel techniques in the field of wavefront shaping have enabled light to be focused deep inside or through scattering media such as biological tissue. However, most of these demonstrations have been limited to thin, static samples since these techniques are very sensitive to changes in the arrangement of the scatterers within. As the samples of interest get thicker, the influence of the dynamic nature of the sample becomes even more pronounced and the window of time in which the wavefront solutions remain valid shrinks further. In this paper, we examine the time scales upon which this decorrelation happens in acute rat brain slices via multispeckle diffusing wave spectroscopy and investigate the relationship between this decorrelation time and the thickness of the sample using diffusing wave spectroscopy theory and Monte Carlo photon transport simulation.", "date": "2016-02-01", "date_type": "published", "publication": "Journal of the Optical Society of America A", "volume": "33", "number": "2", "publisher": "Optical Society of America", "pagerange": "270-275", "id_number": "CaltechAUTHORS:20160218-123702274", "issn": "1084-7529", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160218-123702274", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH Postdoctoral Fellowship", "grant_number": "1F31EB021153-01" }, { "agency": "NIH", "grant_number": "1U01NS090577-01" }, { "agency": "NIH", "grant_number": "1DP2OD007307-01" }, { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "GIST-Caltech Research Collaboration", "grant_number": "CG2012" }, { "agency": "NIH Predoctoral Fellowship" }, { "agency": "National Institute of Neurological Disorders and Stroke (NINDS)" }, { "agency": "National Institute of Biomedical Imaging and Bioengineering" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1364/JOSAA.33.000270", "pmcid": "PMC4783160", "primary_object": { "basename": "josaa-33-2-270.pdf", "url": "https://authors.library.caltech.edu/records/awp3m-dpp59/files/josaa-33-2-270.pdf" }, "pub_year": "2016", "author_list": "Brake, Joshua; Jang, Mooseok; et el." }, { "id": "https://authors.library.caltech.edu/records/prccp-69p15", "eprint_id": 57687, "eprint_status": "archive", "datestamp": "2023-09-15 05:01:40", "lastmod": "2023-10-23 21:12:36", "type": "article", "metadata_visibility": "show", "creators": { "items": [ { "id": "Trivedi-Vikas", "name": { "family": "Trivedi", "given": "Vikas" }, "orcid": "0000-0003-0953-0553" }, { "id": "Truong-Thai-V", "name": { "family": "Truong", "given": "Thai V." } }, { "id": "Trinh-Le-A", "name": { "family": "Trinh", "given": "Le A." } }, { "id": "Holland-Daniel-B", "name": { "family": "Holland", "given": "Daniel B." }, "orcid": "0000-0002-3404-4939" }, { "id": "Liebling-Michael", "name": { "family": "Liebling", "given": "Michael" } }, { "id": "Fraser-S-E", "name": { "family": "Fraser", "given": "Scott E." }, "orcid": "0000-0002-5377-0223" } ] }, "title": "Dynamic structure and protein expression of the live embryonic heart captured by 2-photon light sheet microscopy and retrospective registration", "ispublished": "pub", "full_text_status": "public", "note": "\u00a9 2015 Optical Society of America.\n\nReceived 12 Mar 2015; revised 25 Apr 2015; accepted 1 May 2015; published 11 May 2015.\n\nThis work was funded by Rosen Center for Bioengineering, Caltech, Center of Excellence in Genomic Science (Caltech), NIH/NHGRI Grant # P50HR004071 and FaceBase, NIH Grant # U01DE020063. We thank Leigh Ann Fletcher, Colleen Paquette and Andrey Andreev for fish care.\n\nPublished - boe-6-6-2056.pdf
", "abstract": "We present an imaging and image reconstruction pipeline that captures the dynamic three-dimensional beating motion of the live embryonic zebrafish heart at subcellular resolution. Live, intact zebrafish embryos were imaged using 2-photon light sheet microscopy, which offers deep and fast imaging at 70 frames per second, and the individual optical sections were assembled into a full 4D reconstruction of the beating heart using an optimized retrospective image registration algorithm. This imaging and reconstruction platform permitted us to visualize protein expression patterns at endogenous concentrations in zebrafish gene trap lines.", "date": "2015-06-01", "date_type": "published", "publication": "Biomedical Optics Express", "volume": "6", "number": "6", "publisher": "Optical Society of America", "pagerange": "2056-2066", "id_number": "CaltechAUTHORS:20150520-085804089", "issn": "2156-7085", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20150520-085804089", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Donna and Benjamin M. Rosen Bioengineering Center" }, { "agency": "NIH", "grant_number": "P50HR004071" }, { "agency": "FaceBase" }, { "agency": "NIH", "grant_number": "U01DE020063" } ] }, "local_group": { "items": [ { "id": "Rosen-Bioengineering-Center" } ] }, "doi": "10.1364/BOE.6.002056", "pmcid": "PMC4473743", "primary_object": { "basename": "boe-6-6-2056.pdf", "url": "https://authors.library.caltech.edu/records/prccp-69p15/files/boe-6-6-2056.pdf" }, "pub_year": "2015", "author_list": "Trivedi, Vikas; Truong, Thai V.; et el." } ]