[{"oa_version":"Published Version","_id":"19857","issue":"6","year":"2025","title":"A bacterial toxin-antitoxin system as a native defence element against RNA phages","article_processing_charge":"Yes (via OA deal)","month":"06","pmid":1,"status":"public","date_published":"2025-06-11T00:00:00Z","scopus_import":"1","abstract":[{"text":"Bacteria have evolved a wide range of defence strategies to protect themselves against bacterial viruses (phages). Most known bacterial antiphage defence systems target phages with DNA genomes, which raises the question of how bacteria defend against phages with RNA genomes. Bacterial toxin–antitoxin systems that cleave intracellular RNA could potentially protect bacteria against RNA phages, but this has not been explored experimentally. In this study, we investigated the role of a model toxin–antitoxin system, MazEF, in protecting Escherichia coli against two RNA phage species. When challenged with these phages, the native presence of mazEF moderately reduced population susceptibility and increased the survival of individual E. coli cells. Genomic analysis further revealed an underrepresentation of the MazF cleavage site in genomes of RNA phages infecting E. coli, indicating selection against cleavage. These results show that, in addition to other physiological roles, RNA-degrading toxin–antitoxin systems may also help defend against RNA phages.","lang":"eng"}],"ddc":["570"],"acknowledgement":"This work was supported by ISTFELLOW (People Program – Marie Curie Actions of the European Union’s Seventh Framework Program FP7 under REA grant agreement 291734), the FWF (Austrian Science Fund) Elise Richter Program project number V 738 and the Wellcome Trust Institutional Strategic Support Award (WT105618MA), to N.N. M.P. was a Simons Foundation Fellow of the Life Sciences Research Foundation. We are grateful to Kathrin Tomasek, Lisa Butt, Chris Estell, Alys Jepson, Franklin Nobrega, Stefano Pagliara, Remy Chait, Steve West, Vicki Gold, Josh Eaton, Ivana Gudelj and Rob Beardmore for useful discussions and technical support, as well as to Robin Wright, Christian Fitch and Ben Temperton for sharing equipment. We thank Laurence Van Melderen for sharing the strains. We acknowledge the IST Austria Lab Support Facility, LSI Technical Services Team at the University of Exeter and the Translational Research Exchange @ Exeter (TREE) network. N.N. is grateful to Fabrice Gielen for his support.","OA_type":"hybrid","license":"https://creativecommons.org/licenses/by/4.0/","author":[{"orcid":"0000-0001-9068-6090","last_name":"Nikolic","full_name":"Nikolic, Nela","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","first_name":"Nela"},{"last_name":"Pleska","orcid":"0000-0001-7460-7479","first_name":"Maros","full_name":"Pleska, Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-5396-4346","last_name":"Bergmiller","full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","first_name":"Tobias"},{"orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"article_type":"original","publication_status":"published","project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"name":"Bacterial toxin-antitoxin systems as antiphage defense mechanisms","call_identifier":"FWF","grant_number":"V00738","_id":"26956E74-B435-11E9-9278-68D0E5697425"}],"oa":1,"isi":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","file":[{"file_size":1850797,"relation":"main_file","file_id":"19873","date_created":"2025-06-23T11:34:39Z","creator":"dernst","access_level":"open_access","content_type":"application/pdf","file_name":"2025_BiologyLetters_Nikolic.pdf","date_updated":"2025-06-23T11:34:39Z","checksum":"016f644ed068f8609ded306ad26dbd3f","success":1}],"volume":21,"citation":{"short":"N. Nikolic, M. Pleska, T. Bergmiller, C.C. Guet, Biology Letters 21 (2025).","ieee":"N. Nikolic, M. Pleska, T. Bergmiller, and C. C. Guet, “A bacterial toxin-antitoxin system as a native defence element against RNA phages,” <i>Biology Letters</i>, vol. 21, no. 6. The Royal Society, 2025.","ista":"Nikolic N, Pleska M, Bergmiller T, Guet CC. 2025. A bacterial toxin-antitoxin system as a native defence element against RNA phages. Biology Letters. 21(6), 20250080.","mla":"Nikolic, Nela, et al. “A Bacterial Toxin-Antitoxin System as a Native Defence Element against RNA Phages.” <i>Biology Letters</i>, vol. 21, no. 6, 20250080, The Royal Society, 2025, doi:<a href=\"https://doi.org/10.1098/rsbl.2025.0080\">10.1098/rsbl.2025.0080</a>.","apa":"Nikolic, N., Pleska, M., Bergmiller, T., &#38; Guet, C. C. (2025). A bacterial toxin-antitoxin system as a native defence element against RNA phages. <i>Biology Letters</i>. The Royal Society. <a href=\"https://doi.org/10.1098/rsbl.2025.0080\">https://doi.org/10.1098/rsbl.2025.0080</a>","ama":"Nikolic N, Pleska M, Bergmiller T, Guet CC. A bacterial toxin-antitoxin system as a native defence element against RNA phages. <i>Biology Letters</i>. 2025;21(6). doi:<a href=\"https://doi.org/10.1098/rsbl.2025.0080\">10.1098/rsbl.2025.0080</a>","chicago":"Nikolic, Nela, Maros Pleska, Tobias Bergmiller, and Calin C Guet. “A Bacterial Toxin-Antitoxin System as a Native Defence Element against RNA Phages.” <i>Biology Letters</i>. The Royal Society, 2025. <a href=\"https://doi.org/10.1098/rsbl.2025.0080\">https://doi.org/10.1098/rsbl.2025.0080</a>."},"ec_funded":1,"type":"journal_article","doi":"10.1098/rsbl.2025.0080","day":"11","publisher":"The Royal Society","publication":"Biology Letters","publication_identifier":{"issn":["1744-9561"],"eissn":["1744-957X"]},"quality_controlled":"1","language":[{"iso":"eng"}],"intvolume":"        21","corr_author":"1","external_id":{"isi":["001505019800001"],"pmid":["40494395"]},"has_accepted_license":"1","OA_place":"publisher","date_updated":"2025-09-30T13:38:08Z","department":[{"_id":"CaGu"}],"article_number":"20250080","date_created":"2025-06-22T22:02:06Z","file_date_updated":"2025-06-23T11:34:39Z","acknowledged_ssus":[{"_id":"LifeSc"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"}},{"publication":"Genetics","citation":{"chicago":"Grah, Rok, Calin C Guet, Gašper Tkačik, and Mato Lagator. “Linking Molecular Mechanisms to Their Evolutionary Consequences: A Primer.” <i>Genetics</i>. Oxford University Press, 2025. <a href=\"https://doi.org/10.1093/genetics/iyae191\">https://doi.org/10.1093/genetics/iyae191</a>.","ama":"Grah R, Guet CC, Tkačik G, Lagator M. Linking molecular mechanisms to their evolutionary consequences: a primer. <i>Genetics</i>. 2025;229(2). doi:<a href=\"https://doi.org/10.1093/genetics/iyae191\">10.1093/genetics/iyae191</a>","ieee":"R. Grah, C. C. Guet, G. Tkačik, and M. Lagator, “Linking molecular mechanisms to their evolutionary consequences: a primer,” <i>Genetics</i>, vol. 229, no. 2. Oxford University Press, 2025.","mla":"Grah, Rok, et al. “Linking Molecular Mechanisms to Their Evolutionary Consequences: A Primer.” <i>Genetics</i>, vol. 229, no. 2, iyae191, Oxford University Press, 2025, doi:<a href=\"https://doi.org/10.1093/genetics/iyae191\">10.1093/genetics/iyae191</a>.","apa":"Grah, R., Guet, C. C., Tkačik, G., &#38; Lagator, M. (2025). Linking molecular mechanisms to their evolutionary consequences: a primer. <i>Genetics</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/genetics/iyae191\">https://doi.org/10.1093/genetics/iyae191</a>","ista":"Grah R, Guet CC, Tkačik G, Lagator M. 2025. Linking molecular mechanisms to their evolutionary consequences: a primer. Genetics. 229(2), iyae191.","short":"R. Grah, C.C. Guet, G. Tkačik, M. Lagator, Genetics 229 (2025)."},"volume":229,"publisher":"Oxford University Press","doi":"10.1093/genetics/iyae191","day":"01","type":"journal_article","file_date_updated":"2025-04-16T09:41:04Z","date_created":"2025-01-29T08:21:35Z","article_number":"iyae191","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"intvolume":"       229","language":[{"iso":"eng"}],"quality_controlled":"1","publication_identifier":{"eissn":["1943-2631"]},"date_updated":"2025-05-19T14:08:02Z","has_accepted_license":"1","OA_place":"publisher","external_id":{"isi":["001379194200001"],"pmid":["39601269"]},"corr_author":"1","article_processing_charge":"Yes (in subscription journal)","pmid":1,"month":"02","year":"2025","issue":"2","_id":"18936","oa_version":"Published Version","title":"Linking molecular mechanisms to their evolutionary consequences: a primer","article_type":"original","publication_status":"published","author":[{"last_name":"Grah","orcid":"0000-0003-2539-3560","first_name":"Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","full_name":"Grah, Rok"},{"orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"},{"orcid":"0000-0002-6699-1455","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","first_name":"Gašper"},{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato","first_name":"Mato","last_name":"Lagator"}],"file":[{"date_created":"2025-04-16T09:41:04Z","creator":"dernst","access_level":"open_access","content_type":"application/pdf","relation":"main_file","file_size":1511688,"file_id":"19580","checksum":"f730e416795969449ef49d97b82ac494","success":1,"file_name":"2025_Genetics_Grah.pdf","date_updated":"2025-04-16T09:41:04Z"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","isi":1,"oa":1,"scopus_import":"1","date_published":"2025-02-01T00:00:00Z","abstract":[{"lang":"eng","text":"A major obstacle to predictive understanding of evolution stems from the complexity of biological systems, which prevents detailed characterization of key evolutionary properties. Here, we highlight some of the major sources of complexity that arise when relating molecular mechanisms to their evolutionary consequences and ask whether accounting for every mechanistic detail is important to accurately predict evolutionary outcomes. To do this, we developed a mechanistic model of a bacterial promoter regulated by 2 proteins, allowing us to connect any promoter genotype to 6 phenotypes that capture the dynamics of gene expression following an environmental switch. Accounting for the mechanisms that govern how this system works enabled us to provide an in-depth picture of how regulated bacterial promoters might evolve. More importantly, we used the model to explore which factors that contribute to the complexity of this system are essential for understanding its evolution, and which can be simplified without information loss. We found that several key evolutionary properties—the distribution of phenotypic and fitness effects of mutations, the evolutionary trajectories during selection for regulation—can be accurately captured without accounting for all, or even most, parameters of the system. Our findings point to the need for a mechanistic approach to studying evolution, as it enables tackling biological complexity and in doing so improves the ability to predict evolutionary outcomes."}],"status":"public","OA_type":"hybrid","acknowledgement":"The authors thank Nick Barton, Stepan Denisov, Claudia Igler, Srdjan Sarikas, Anna Staron, and the anonymous reviewers for useful comments and discussions that helped improve our work.\r\nFunding for this work was provided by the Wellcome Trust–Royal Society Sir Henry Dale Fellowship (216779/Z/19/Z) and the Royal Society Research Grant (RG\\R2\\232522) to M.L.","ddc":["570"]},{"month":"04","pmid":1,"article_processing_charge":"Yes (in subscription journal)","title":"Pulsatile basal gene expression as a fitness determinant in bacteria","oa_version":"Published Version","year":"2025","_id":"19626","issue":"15","oa":1,"file":[{"file_id":"19888","file_size":2949523,"relation":"main_file","content_type":"application/pdf","access_level":"open_access","date_created":"2025-06-24T07:27:43Z","creator":"dernst","date_updated":"2025-06-24T07:27:43Z","file_name":"2025_PNAS_Jain.pdf","success":1,"checksum":"115a687f40009660eb4b38b4f6559d41"}],"isi":1,"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","author":[{"orcid":"0000-0002-3809-0449","last_name":"Jain","full_name":"Jain, Kirti","id":"330F0278-F248-11E8-B48F-1D18A9856A87","first_name":"Kirti"},{"last_name":"Hauschild","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert","first_name":"Robert"},{"orcid":"0000-0003-1006-6639","last_name":"Bochkareva","full_name":"Bochkareva, Olga","id":"C4558D3C-6102-11E9-A62E-F418E6697425","first_name":"Olga"},{"first_name":"Roderich","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","full_name":"Römhild, Roderich","orcid":"0000-0001-9480-5261","last_name":"Römhild"},{"last_name":"Tkačik","orcid":"0000-0002-6699-1455","first_name":"Gašper","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Guet","orcid":"0000-0001-6220-2052","first_name":"Calin C","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"project":[{"_id":"c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473","grant_number":"CZI01","name":"Tools for automation and feedback microscopy"},{"grant_number":"E219","_id":"bd6f94d1-d553-11ed-ba76-ae9f07250f74","name":"Non-canonical antibiotic interactions"},{"name":"Evolutionary analysis of gene regulation","_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181","grant_number":"I05127"}],"article_type":"original","publication_status":"published","acknowledgement":"K.J. thanks B. Wu, I. Tomanek, K. Tomasek for detailed discussions on the manuscript, all other members from the Guet laboratory for valuable feedback, R. Chait, & Imaging and Optics Facility, Institute of Science and Technology Austria for helping with microscopy, Dr. Sudha Rao and Dr. Raja Mugasimangalam, Genotypic Technology India for allowing time off to address the revisions. K.J. acknowledges Institute of Science and Technology fellowship IC1006FELL02, R.H. was supported in part by Chan Zuckerberg Initiative and Donor Advised-Fund grant 2020-225401 (https://doi.org/10.37921/120055ratwvi), O.O.B. acknowledges Fonds Zur Förderung der Wissenschaftlichen Forschung (FWF) Grant ESP253-B, R.R. acknowledges FWF Grant 10.55776/ESP219, C.C.G. acknowledges FWF I5127-B.","ddc":["570"],"OA_type":"hybrid","status":"public","scopus_import":"1","abstract":[{"text":"Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of nonfunctional “promoter leakiness,” merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the noncanonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g., control of costly-to-induce multidrug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multidrug resistance is crucial for effective public health measures.","lang":"eng"}],"date_published":"2025-04-15T00:00:00Z","publication":"Proceedings of the National Academy of Sciences","related_material":{"link":[{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/clockwork-just-for-antibiotic-resistance/"}],"record":[{"status":"public","id":"19294","relation":"research_data"}]},"type":"journal_article","day":"15","publisher":"National Academy of Sciences","doi":"10.1073/pnas.2413709122","volume":122,"citation":{"chicago":"Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper Tkačik, and Calin C Guet. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2413709122\">https://doi.org/10.1073/pnas.2413709122</a>.","ama":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Pulsatile basal gene expression as a fitness determinant in bacteria. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(15). doi:<a href=\"https://doi.org/10.1073/pnas.2413709122\">10.1073/pnas.2413709122</a>","ieee":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet, “Pulsatile basal gene expression as a fitness determinant in bacteria,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15. National Academy of Sciences, 2025.","mla":"Jain, Kirti, et al. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15, e2413709122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2413709122\">10.1073/pnas.2413709122</a>.","apa":"Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., &#38; Guet, C. C. (2025). Pulsatile basal gene expression as a fitness determinant in bacteria. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2413709122\">https://doi.org/10.1073/pnas.2413709122</a>","ista":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Pulsatile basal gene expression as a fitness determinant in bacteria. Proceedings of the National Academy of Sciences. 122(15), e2413709122.","short":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, Proceedings of the National Academy of Sciences 122 (2025)."},"acknowledged_ssus":[{"_id":"Bio"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_number":"e2413709122","department":[{"_id":"CaGu"},{"_id":"Bio"},{"_id":"FyKo"},{"_id":"GaTk"}],"file_date_updated":"2025-06-24T07:27:43Z","date_created":"2025-04-27T22:02:13Z","external_id":{"isi":["001471235200001"],"pmid":["40193613"]},"corr_author":"1","date_updated":"2026-04-28T13:35:46Z","has_accepted_license":"1","OA_place":"publisher","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"intvolume":"       122","language":[{"iso":"eng"}],"quality_controlled":"1"},{"abstract":[{"text":"Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of non-functional “promoter leakiness”, merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the non-canonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g. control of costly-to-induce multi-drug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multi-drug resistance is crucial for effective public health measures.","lang":"eng"}],"date_published":"2025-03-04T00:00:00Z","status":"public","OA_type":"gold","OA_place":"repository","has_accepted_license":"1","date_updated":"2026-04-28T13:35:45Z","corr_author":"1","ddc":["570"],"file_date_updated":"2025-03-05T07:39:38Z","date_created":"2025-03-04T13:27:21Z","department":[{"_id":"CaGu"},{"_id":"Bio"},{"_id":"FyKo"},{"_id":"GaTk"}],"author":[{"id":"330F0278-F248-11E8-B48F-1D18A9856A87","full_name":"Jain, Kirti","first_name":"Kirti","orcid":"0000-0002-3809-0449","last_name":"Jain"},{"first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert","last_name":"Hauschild","orcid":"0000-0001-9843-3522"},{"orcid":"0000-0003-1006-6639","last_name":"Bochkareva","full_name":"Bochkareva, Olga","id":"C4558D3C-6102-11E9-A62E-F418E6697425","first_name":"Olga"},{"orcid":"0000-0001-9480-5261","last_name":"Römhild","first_name":"Roderich","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","full_name":"Römhild, Roderich"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","first_name":"Gašper","orcid":"0000-0002-6699-1455","last_name":"Tkačik"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"file":[{"file_name":"Data1.xlsx","date_updated":"2025-03-04T13:08:52Z","success":1,"checksum":"11a5bab307a4e1e1598a1577d8a2fbb5","file_id":"19295","relation":"main_file","file_size":269054,"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","creator":"dernst","date_created":"2025-03-04T13:08:52Z","access_level":"open_access"},{"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","date_created":"2025-03-04T13:08:52Z","creator":"dernst","access_level":"open_access","file_id":"19296","file_size":87143,"relation":"main_file","success":1,"checksum":"3b057894322639f0c1e11fb2e84173e6","file_name":"Data2.xlsx","date_updated":"2025-03-04T13:08:52Z"},{"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","creator":"dernst","date_created":"2025-03-04T13:08:52Z","access_level":"open_access","file_id":"19297","relation":"main_file","file_size":129101,"success":1,"checksum":"a551e1b79a138bb97ab96979aa475b3c","file_name":"Data3.xlsx","date_updated":"2025-03-04T13:08:52Z"},{"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","access_level":"open_access","date_created":"2025-03-04T13:08:52Z","creator":"dernst","file_id":"19298","relation":"main_file","file_size":86243,"success":1,"checksum":"d6909c9bf111f859058082b1a2f970c4","date_updated":"2025-03-04T13:08:52Z","file_name":"Data4.xlsx"},{"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","access_level":"open_access","date_created":"2025-03-04T13:08:52Z","creator":"dernst","file_id":"19299","relation":"main_file","file_size":26049,"success":1,"checksum":"e5725a3a118a3f06846104906c8792c7","date_updated":"2025-03-04T13:08:52Z","file_name":"Data5.xlsx"},{"date_updated":"2025-03-04T13:08:52Z","file_name":"RawData_2_3.xlsx","success":1,"checksum":"16763c127049f14bd587dc885677dce1","file_id":"19300","file_size":7327253,"relation":"main_file","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","access_level":"open_access","creator":"dernst","date_created":"2025-03-04T13:08:52Z"},{"success":1,"checksum":"2f3e1a368b4e3abc46bf37e02724f0f4","date_updated":"2025-03-05T07:39:38Z","file_name":"Readme.txt","content_type":"text/plain","access_level":"open_access","date_created":"2025-03-05T07:39:38Z","creator":"dernst","file_id":"19301","relation":"main_file","file_size":606}],"oa":1,"_id":"19294","citation":{"ama":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Data for “Pulsatile basal gene expression as a fitness determinant in bacteria.” 2025. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:19294\">10.15479/AT:ISTA:19294</a>","chicago":"Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper Tkačik, and Calin C Guet. “Data for ‘Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.’” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT:ISTA:19294\">https://doi.org/10.15479/AT:ISTA:19294</a>.","short":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, (2025).","ieee":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet, “Data for ‘Pulsatile basal gene expression as a fitness determinant in bacteria.’” Institute of Science and Technology Austria, 2025.","apa":"Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., &#38; Guet, C. C. (2025). Data for “Pulsatile basal gene expression as a fitness determinant in bacteria.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:19294\">https://doi.org/10.15479/AT:ISTA:19294</a>","mla":"Jain, Kirti, et al. <i>Data for “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.”</i> Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:19294\">10.15479/AT:ISTA:19294</a>.","ista":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Data for ‘Pulsatile basal gene expression as a fitness determinant in bacteria’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:19294\">10.15479/AT:ISTA:19294</a>."},"year":"2025","oa_version":"Published Version","day":"04","doi":"10.15479/AT:ISTA:19294","publisher":"Institute of Science and Technology Austria","type":"research_data","related_material":{"record":[{"relation":"used_in_publication","id":"19626","status":"public"}]},"title":"Data for \"Pulsatile basal gene expression as a fitness determinant in bacteria\"","article_processing_charge":"No","month":"03"},{"day":"20","doi":"10.3389/fmicb.2023.1049255","publisher":"Frontiers","type":"journal_article","citation":{"chicago":"Guet, Calin C, L Bruneaux, P Oikonomou, M Aldana, and P Cluzel. “Monitoring Lineages of Growing and Dividing Bacteria Reveals an Inducible Memory of <i>Mar</i> Operon Expression.” <i>Frontiers in Microbiology</i>. Frontiers, 2023. <a href=\"https://doi.org/10.3389/fmicb.2023.1049255\">https://doi.org/10.3389/fmicb.2023.1049255</a>.","ama":"Guet CC, Bruneaux L, Oikonomou P, Aldana M, Cluzel P. Monitoring lineages of growing and dividing bacteria reveals an inducible memory of <i>mar</i> operon expression. <i>Frontiers in Microbiology</i>. 2023;14. doi:<a href=\"https://doi.org/10.3389/fmicb.2023.1049255\">10.3389/fmicb.2023.1049255</a>","ieee":"C. C. Guet, L. Bruneaux, P. Oikonomou, M. Aldana, and P. Cluzel, “Monitoring lineages of growing and dividing bacteria reveals an inducible memory of <i>mar</i> operon expression,” <i>Frontiers in Microbiology</i>, vol. 14. Frontiers, 2023.","apa":"Guet, C. C., Bruneaux, L., Oikonomou, P., Aldana, M., &#38; Cluzel, P. (2023). Monitoring lineages of growing and dividing bacteria reveals an inducible memory of <i>mar</i> operon expression. <i>Frontiers in Microbiology</i>. Frontiers. <a href=\"https://doi.org/10.3389/fmicb.2023.1049255\">https://doi.org/10.3389/fmicb.2023.1049255</a>","ista":"Guet CC, Bruneaux L, Oikonomou P, Aldana M, Cluzel P. 2023. Monitoring lineages of growing and dividing bacteria reveals an inducible memory of <i>mar</i> operon expression. Frontiers in Microbiology. 14, 1049255.","mla":"Guet, Calin C., et al. “Monitoring Lineages of Growing and Dividing Bacteria Reveals an Inducible Memory of <i>Mar</i> Operon Expression.” <i>Frontiers in Microbiology</i>, vol. 14, 1049255, Frontiers, 2023, doi:<a href=\"https://doi.org/10.3389/fmicb.2023.1049255\">10.3389/fmicb.2023.1049255</a>.","short":"C.C. Guet, L. Bruneaux, P. Oikonomou, M. Aldana, P. Cluzel, Frontiers in Microbiology 14 (2023)."},"volume":14,"publication":"Frontiers in Microbiology","date_updated":"2024-10-09T21:03:59Z","has_accepted_license":"1","external_id":{"isi":["001030002600001"],"pmid":["37485524"]},"corr_author":"1","intvolume":"        14","quality_controlled":"1","language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1664-302X"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"file_date_updated":"2023-07-31T07:16:34Z","date_created":"2023-02-02T08:13:28Z","article_number":"1049255","department":[{"_id":"CaGu"}],"title":"Monitoring lineages of growing and dividing bacteria reveals an inducible memory of <i>mar</i> operon expression","year":"2023","_id":"12478","oa_version":"Published Version","pmid":1,"month":"06","article_processing_charge":"Yes","acknowledgement":"This work was supported by NIH P50 award P50GM081892-02 to the University of Chicago, a catalyst grant from the Chicago Biomedical Consortium with support from The Searle Funds at The Chicago Community Trust to PC, and a Yen Fellowship to CCG. MA was partially supported by PAPIIT-UNAM grant IN-11322.","ddc":["570"],"date_published":"2023-06-20T00:00:00Z","scopus_import":"1","abstract":[{"text":"In Gram negative bacteria, the multiple antibiotic resistance or mar operon, is known to control the expression of multi-drug efflux genes that protect bacteria from a wide range of drugs. As many different chemical compounds can induce this operon, identifying the parameters that govern the dynamics of its induction is crucial to better characterize the processes of tolerance and resistance. Most experiments have assumed that the properties of the mar transcriptional network can be inferred from population measurements. However, measurements from an asynchronous population of cells can mask underlying phenotypic variations of single cells. We monitored the activity of the mar promoter in single Escherichia coli cells in linear micro-colonies and established that the response to a steady level of inducer was most heterogeneous within individual colonies for an intermediate value of inducer. Specifically, sub-lineages defined by contiguous daughter-cells exhibited similar promoter activity, whereas activity was greatly variable between different sub-lineages. Specific sub-trees of uniform promoter activity persisted over several generations. Statistical analyses of the lineages suggest that the presence of these sub-trees is the signature of an inducible memory of the promoter state that is transmitted from mother to daughter cells. This single-cell study reveals that the degree of epigenetic inheritance changes as a function of inducer concentration, suggesting that phenotypic inheritance may be an inducible phenotype.","lang":"eng"}],"status":"public","file":[{"date_updated":"2023-07-31T07:16:34Z","file_name":"2023_FrontiersMicrobiology_Guet.pdf","success":1,"checksum":"7dd322347512afaa5daf72a0154f2f07","file_id":"13322","relation":"main_file","file_size":6452841,"content_type":"application/pdf","access_level":"open_access","date_created":"2023-07-31T07:16:34Z","creator":"dernst"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","isi":1,"oa":1,"publication_status":"published","article_type":"original","author":[{"first_name":"Calin C","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet"},{"last_name":"Bruneaux","full_name":"Bruneaux, L","first_name":"L"},{"full_name":"Oikonomou, P","first_name":"P","last_name":"Oikonomou"},{"first_name":"M","full_name":"Aldana, M","last_name":"Aldana"},{"first_name":"P","full_name":"Cluzel, P","last_name":"Cluzel"}]},{"oa_version":"Published Version","year":"2022","_id":"11843","title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","article_processing_charge":"Yes","month":"07","pmid":1,"status":"public","date_published":"2022-07-26T00:00:00Z","abstract":[{"lang":"eng","text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both rate-limiting factors of T cell activation. This response was binary at the single-cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease."}],"scopus_import":"1","acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89, and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373), and the Austrian Science Fund (FWF P29911) to MS.","ddc":["570"],"author":[{"first_name":"Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","full_name":"Tomasek, Kathrin","orcid":"0000-0003-3768-877X","last_name":"Tomasek"},{"first_name":"Alexander F","full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X","last_name":"Leithner"},{"last_name":"Glatzová","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d","full_name":"Glatzová, Ivana","first_name":"Ivana"},{"last_name":"Lukesch","full_name":"Lukesch, Michael S.","first_name":"Michael S."},{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"},{"orcid":"0000-0002-6620-9179","last_name":"Sixt","first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"}],"project":[{"name":"Cellular Navigation Along Spatial Gradients","call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373"},{"name":"Mechanical adaptation of lamellipodial actin","call_identifier":"FWF","_id":"26018E70-B435-11E9-9278-68D0E5697425","grant_number":"P29911"}],"article_type":"original","publication_status":"published","oa":1,"file":[{"checksum":"002a3c7c7ea5caa9af9cfbea308f6ea4","success":1,"date_updated":"2022-08-16T08:57:37Z","file_name":"2022_eLife_Tomasek.pdf","access_level":"open_access","date_created":"2022-08-16T08:57:37Z","creator":"cchlebak","content_type":"application/pdf","file_size":2057577,"relation":"main_file","file_id":"11861"}],"isi":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","volume":11,"citation":{"apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. eLife. 11, e78995.","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>, vol. 11, e78995, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>.","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, ELife 11 (2022).","chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>.","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>"},"related_material":{"record":[{"relation":"earlier_version","id":"10316","status":"public"}]},"ec_funded":1,"type":"journal_article","publisher":"eLife Sciences Publications","day":"26","doi":"10.7554/eLife.78995","publication":"eLife","publication_identifier":{"eissn":["2050-084X"]},"intvolume":"        11","language":[{"iso":"eng"}],"quality_controlled":"1","external_id":{"isi":["000838410200001"],"pmid":["35881547"]},"corr_author":"1","date_updated":"2025-04-15T07:17:32Z","has_accepted_license":"1","article_number":"e78995","department":[{"_id":"MiSi"},{"_id":"CaGu"}],"date_created":"2022-08-14T22:01:46Z","file_date_updated":"2022-08-16T08:57:37Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"}},{"publication":"eLife","publisher":"eLife Sciences Publications","doi":"10.7554/ELIFE.82240","day":"22","related_material":{"link":[{"relation":"software","url":"https://doi.org/10.5281/zenodo.6974122"}],"record":[{"status":"public","relation":"research_data","id":"12339"}]},"type":"journal_article","citation":{"ama":"Tomanek I, Guet CC. Adaptation dynamics between copynumber and point mutations. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/ELIFE.82240\">10.7554/ELIFE.82240</a>","chicago":"Tomanek, Isabella, and Calin C Guet. “Adaptation Dynamics between Copynumber and Point Mutations.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/ELIFE.82240\">https://doi.org/10.7554/ELIFE.82240</a>.","short":"I. Tomanek, C.C. Guet, ELife 11 (2022).","ieee":"I. Tomanek and C. C. Guet, “Adaptation dynamics between copynumber and point mutations,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","ista":"Tomanek I, Guet CC. 2022. Adaptation dynamics between copynumber and point mutations. eLife. 11, e82240.","apa":"Tomanek, I., &#38; Guet, C. C. (2022). Adaptation dynamics between copynumber and point mutations. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/ELIFE.82240\">https://doi.org/10.7554/ELIFE.82240</a>","mla":"Tomanek, Isabella, and Calin C. Guet. “Adaptation Dynamics between Copynumber and Point Mutations.” <i>ELife</i>, vol. 11, e82240, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/ELIFE.82240\">10.7554/ELIFE.82240</a>."},"volume":11,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"date_created":"2023-01-22T23:00:55Z","file_date_updated":"2023-01-23T08:56:21Z","article_number":"e82240","department":[{"_id":"CaGu"}],"date_updated":"2025-03-06T14:03:50Z","has_accepted_license":"1","external_id":{"pmid":["36546673"],"isi":["000912674700001"]},"corr_author":"1","intvolume":"        11","language":[{"iso":"eng"}],"quality_controlled":"1","publication_identifier":{"eissn":["2050-084X"]},"pmid":1,"month":"12","article_processing_charge":"No","title":"Adaptation dynamics between copynumber and point mutations","year":"2022","_id":"12333","oa_version":"Published Version","file":[{"content_type":"application/pdf","access_level":"open_access","date_created":"2023-01-23T08:56:21Z","creator":"dernst","file_id":"12338","relation":"main_file","file_size":8835954,"success":1,"checksum":"9321fd5f06ff59d5e2d33daee84b3da1","date_updated":"2023-01-23T08:56:21Z","file_name":"2022_eLife_Tomanek.pdf"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","isi":1,"oa":1,"publication_status":"published","article_type":"original","author":[{"orcid":"0000-0001-6197-363X","last_name":"Tomanek","full_name":"Tomanek, Isabella","id":"3981F020-F248-11E8-B48F-1D18A9856A87","first_name":"Isabella"},{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052"}],"acknowledgement":"We are grateful to N Barton, F Kondrashov, M Lagator, M Pleska, R Roemhild, D Siekhaus, and G\r\nTkacik for input on the manuscript and to K Tomasek for help with flow cytometry.","ddc":["570"],"abstract":[{"text":"Together, copy-number and point mutations form the basis for most evolutionary novelty, through the process of gene duplication and divergence. While a plethora of genomic data reveals the long-term fate of diverging coding sequences and their cis-regulatory elements, little is known about the early dynamics around the duplication event itself. In microorganisms, selection for increased gene expression often drives the expansion of gene copy-number mutations, which serves as a crude adaptation, prior to divergence through refining point mutations. Using a simple synthetic genetic reporter system that can distinguish between copy-number and point mutations, we study their early and transient adaptive dynamics in real time in Escherichia coli. We find two qualitatively different routes of adaptation, depending on the level of functional improvement needed. In conditions of high gene expression demand, the two mutation types occur as a combination. However, under low gene expression demand, copy-number and point mutations are mutually exclusive; here, owing to their higher frequency, adaptation is dominated by copy-number mutations, in a process we term amplification hindrance. Ultimately, due to high reversal rates and pleiotropic cost, copy-number mutations may not only serve as a crude and transient adaptation, but also constrain sequence divergence over evolutionary time scales.","lang":"eng"}],"scopus_import":"1","date_published":"2022-12-22T00:00:00Z","status":"public"},{"day":"23","doi":"10.5061/dryad.rfj6q57ds","publisher":"Dryad","type":"research_data_reference","related_material":{"record":[{"id":"12333","relation":"used_in_publication","status":"public"}]},"title":"Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose","_id":"12339","citation":{"ama":"Tomanek I, Guet CC. Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose. 2022. doi:<a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">10.5061/dryad.rfj6q57ds</a>","chicago":"Tomanek, Isabella, and Calin C Guet. “Flow Cytometry YFP and CFP Data and Deep Sequencing Data of Populations Evolving in Galactose.” Dryad, 2022. <a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">https://doi.org/10.5061/dryad.rfj6q57ds</a>.","short":"I. Tomanek, C.C. Guet, (2022).","apa":"Tomanek, I., &#38; Guet, C. C. (2022). Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose. Dryad. <a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">https://doi.org/10.5061/dryad.rfj6q57ds</a>","ista":"Tomanek I, Guet CC. 2022. Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose, Dryad, <a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">10.5061/dryad.rfj6q57ds</a>.","mla":"Tomanek, Isabella, and Calin C. Guet. <i>Flow Cytometry YFP and CFP Data and Deep Sequencing Data of Populations Evolving in Galactose</i>. Dryad, 2022, doi:<a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">10.5061/dryad.rfj6q57ds</a>.","ieee":"I. Tomanek and C. C. Guet, “Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose.” Dryad, 2022."},"year":"2022","oa_version":"Published Version","main_file_link":[{"open_access":"1","url":"https://doi.org/10.5061/dryad.rfj6q57ds"}],"month":"12","article_processing_charge":"No","date_updated":"2025-03-06T14:03:50Z","corr_author":"1","ddc":["570"],"date_published":"2022-12-23T00:00:00Z","abstract":[{"lang":"eng","text":"Copy-number and point mutations form the basis for most evolutionary novelty through the process of gene duplication and divergence. While a plethora of genomic sequence data reveals the long-term fate of diverging coding sequences and their cis-regulatory elements, little is known about the early dynamics around the duplication event itself. In microorganisms, selection for increased gene expression often drives the expansion of gene copy-number mutations, which serves as a crude adaptation, prior to divergence through refining point mutations. Using a simple synthetic genetic system that allows us to distinguish copy-number and point mutations, we study their early and transient adaptive dynamics in real-time in Escherichia coli. We find two qualitatively different routes of adaptation depending on the level of functional improvement selected for: In conditions of high gene expression demand, the two types of mutations occur as a combination. Under low gene expression demand, negative epistasis between the two types of mutations renders them mutually exclusive. Thus, owing to their higher frequency, adaptation is dominated by copy-number mutations. Ultimately, due to high rates of reversal and pleiotropic cost, copy-number mutations may not only serve as a crude and transient adaptation but also constrain sequence divergence over evolutionary time scales."}],"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"date_created":"2023-01-23T09:00:37Z","department":[{"_id":"CaGu"}],"author":[{"id":"3981F020-F248-11E8-B48F-1D18A9856A87","full_name":"Tomanek, Isabella","first_name":"Isabella","last_name":"Tomanek","orcid":"0000-0001-6197-363X"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"}]},{"acknowledgement":"We thank Hande Acar, Nicholas H Barton, Rok Grah, Tiago Paixao, Maros Pleska, Anna Staron, and Murat Tugrul for insightful comments and input on the manuscript. This work was supported by: Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 216779/Z/19/Z) to ML; IPC Grant from IST Austria to ML and SS; European Research Council Funding Programme 7 (2007–2013, grant agreement number 648440) to JPB.","ddc":["576"],"status":"public","scopus_import":"1","abstract":[{"lang":"eng","text":"Predicting function from sequence is a central problem of biology. Currently, this is possible only locally in a narrow mutational neighborhood around a wildtype sequence rather than globally from any sequence. Using random mutant libraries, we developed a biophysical model that accounts for multiple features of σ70 binding bacterial promoters to predict constitutive gene expression levels from any sequence. We experimentally and theoretically estimated that 10–20% of random sequences lead to expression and ~80% of non-expressing sequences are one mutation away from a functional promoter. The potential for generating expression from random sequences is so pervasive that selection acts against σ70-RNA polymerase binding sites even within inter-genic, promoter-containing regions. This pervasiveness of σ70-binding sites implies that emergence of promoters is not the limiting step in gene regulatory evolution. Ultimately, the inclusion of novel features of promoter function into a mechanistic model enabled not only more accurate predictions of gene expression levels, but also identified that promoters evolve more rapidly than previously thought."}],"date_published":"2022-01-26T00:00:00Z","oa":1,"file":[{"file_size":5604343,"relation":"main_file","file_id":"10739","access_level":"open_access","date_created":"2022-02-07T07:14:09Z","creator":"cchlebak","content_type":"application/pdf","date_updated":"2022-02-07T07:14:09Z","file_name":"2022_ELife_Lagator.pdf","checksum":"decdcdf600ff51e9a9703b49ca114170","success":1}],"isi":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Lagator","full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato"},{"first_name":"Srdjan","id":"35F0286E-F248-11E8-B48F-1D18A9856A87","full_name":"Sarikas, Srdjan","last_name":"Sarikas"},{"last_name":"Steinrück","orcid":"0000-0003-1229-9719","first_name":"Magdalena","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","full_name":"Steinrück, Magdalena"},{"last_name":"Toledo-Aparicio","first_name":"David","full_name":"Toledo-Aparicio, David"},{"first_name":"Jonathan P","full_name":"Bollback, Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","last_name":"Bollback","orcid":"0000-0002-4624-4612"},{"first_name":"Calin C","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet"},{"first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455"}],"project":[{"call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer","_id":"2578D616-B435-11E9-9278-68D0E5697425","grant_number":"648440"}],"article_type":"original","publication_status":"published","title":"Predicting bacterial promoter function and evolution from random sequences","oa_version":"Published Version","year":"2022","_id":"10736","month":"01","pmid":1,"article_processing_charge":"No","external_id":{"pmid":["35080492"],"isi":["000751104400001"]},"corr_author":"1","date_updated":"2025-03-31T16:00:23Z","has_accepted_license":"1","publication_identifier":{"eissn":["2050-084X"]},"intvolume":"        11","quality_controlled":"1","language":[{"iso":"eng"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_number":"e64543","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"NiBa"}],"file_date_updated":"2022-02-07T07:14:09Z","date_created":"2022-02-06T23:01:32Z","ec_funded":1,"type":"journal_article","publisher":"eLife Sciences Publications","day":"26","doi":"10.7554/eLife.64543","volume":11,"citation":{"ama":"Lagator M, Sarikas S, Steinrück M, et al. Predicting bacterial promoter function and evolution from random sequences. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.64543\">10.7554/eLife.64543</a>","chicago":"Lagator, Mato, Srdjan Sarikas, Magdalena Steinrück, David Toledo-Aparicio, Jonathan P Bollback, Calin C Guet, and Gašper Tkačik. “Predicting Bacterial Promoter Function and Evolution from Random Sequences.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.64543\">https://doi.org/10.7554/eLife.64543</a>.","short":"M. Lagator, S. Sarikas, M. Steinrück, D. Toledo-Aparicio, J.P. Bollback, C.C. Guet, G. Tkačik, ELife 11 (2022).","apa":"Lagator, M., Sarikas, S., Steinrück, M., Toledo-Aparicio, D., Bollback, J. P., Guet, C. C., &#38; Tkačik, G. (2022). Predicting bacterial promoter function and evolution from random sequences. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.64543\">https://doi.org/10.7554/eLife.64543</a>","mla":"Lagator, Mato, et al. “Predicting Bacterial Promoter Function and Evolution from Random Sequences.” <i>ELife</i>, vol. 11, e64543, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.64543\">10.7554/eLife.64543</a>.","ista":"Lagator M, Sarikas S, Steinrück M, Toledo-Aparicio D, Bollback JP, Guet CC, Tkačik G. 2022. Predicting bacterial promoter function and evolution from random sequences. eLife. 11, e64543.","ieee":"M. Lagator <i>et al.</i>, “Predicting bacterial promoter function and evolution from random sequences,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022."},"publication":"eLife"},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"file_date_updated":"2021-03-23T10:12:58Z","date_created":"2021-03-23T10:11:46Z","article_number":"e65993","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"date_updated":"2025-06-12T06:36:17Z","has_accepted_license":"1","external_id":{"isi":["000631050900001"],"pmid":["33683203"]},"corr_author":"1","intvolume":"        10","language":[{"iso":"eng"}],"quality_controlled":"1","publication_identifier":{"issn":["2050-084X"]},"publication":"eLife","publisher":"eLife Sciences Publications","day":"08","doi":"10.7554/elife.65993","related_material":{"record":[{"relation":"research_data","id":"8951","status":"public"}]},"ec_funded":1,"type":"journal_article","citation":{"ama":"Nagy-Staron AA, Tomasek K, Caruso Carter C, et al. Local genetic context shapes the function of a gene regulatory network. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/elife.65993\">10.7554/elife.65993</a>","chicago":"Nagy-Staron, Anna A, Kathrin Tomasek, Caroline Caruso Carter, Elisabeth Sonnleitner, Bor Kavcic, Tiago Paixão, and Calin C Guet. “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/elife.65993\">https://doi.org/10.7554/elife.65993</a>.","short":"A.A. Nagy-Staron, K. Tomasek, C. Caruso Carter, E. Sonnleitner, B. Kavcic, T. Paixão, C.C. Guet, ELife 10 (2021).","ieee":"A. A. Nagy-Staron <i>et al.</i>, “Local genetic context shapes the function of a gene regulatory network,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","apa":"Nagy-Staron, A. A., Tomasek, K., Caruso Carter, C., Sonnleitner, E., Kavcic, B., Paixão, T., &#38; Guet, C. C. (2021). Local genetic context shapes the function of a gene regulatory network. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.65993\">https://doi.org/10.7554/elife.65993</a>","mla":"Nagy-Staron, Anna A., et al. “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” <i>ELife</i>, vol. 10, e65993, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/elife.65993\">10.7554/elife.65993</a>.","ista":"Nagy-Staron AA, Tomasek K, Caruso Carter C, Sonnleitner E, Kavcic B, Paixão T, Guet CC. 2021. Local genetic context shapes the function of a gene regulatory network. eLife. 10, e65993."},"volume":10,"file":[{"relation":"main_file","file_size":1390469,"file_id":"9284","access_level":"open_access","creator":"bkavcic","date_created":"2021-03-23T10:12:58Z","content_type":"application/pdf","date_updated":"2021-03-23T10:12:58Z","file_name":"elife-65993-v2.pdf","checksum":"3c2f44058c2dd45a5a1027f09d263f8e","success":1}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","isi":1,"oa":1,"project":[{"grant_number":"628377","_id":"2517526A-B435-11E9-9278-68D0E5697425","name":"The Systems Biology of Transcriptional Read-Through in Bacteria: from Synthetic Networks to Genomic Studies","call_identifier":"FP7"},{"grant_number":"I03901","_id":"268BFA92-B435-11E9-9278-68D0E5697425","name":"Cybergenetic circuits to test composability of gene networks","call_identifier":"FWF"}],"publication_status":"published","article_type":"original","author":[{"last_name":"Nagy-Staron","orcid":"0000-0002-1391-8377","full_name":"Nagy-Staron, Anna A","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","first_name":"Anna A"},{"first_name":"Kathrin","full_name":"Tomasek, Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3768-877X","last_name":"Tomasek"},{"full_name":"Caruso Carter, Caroline","first_name":"Caroline","last_name":"Caruso Carter"},{"first_name":"Elisabeth","full_name":"Sonnleitner, Elisabeth","last_name":"Sonnleitner"},{"orcid":"0000-0001-6041-254X","last_name":"Kavcic","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","full_name":"Kavcic, Bor","first_name":"Bor"},{"last_name":"Paixão","first_name":"Tiago","full_name":"Paixão, Tiago"},{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052"}],"acknowledgement":"We thank J Bollback, L Hurst, M Lagator, C Nizak, O Rivoire, M Savageau, G Tkacik, and B Vicozo\r\nfor helpful discussions; A Dolinar and A Greshnova for technical assistance; T Bollenbach for supplying the strain JW0336; C Rusnac, and members of the Guet lab for comments. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n˚\r\n628377 (ANS) and an Austrian Science Fund (FWF) grant n˚ I 3901-B32 (CCG).","ddc":["570"],"abstract":[{"text":"Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic GRN to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one GRN with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit (TU) within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual TUs, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of GRNs.","lang":"eng"}],"date_published":"2021-03-08T00:00:00Z","scopus_import":"1","status":"public","pmid":1,"month":"03","article_processing_charge":"Yes","title":"Local genetic context shapes the function of a gene regulatory network","keyword":["Genetics and Molecular Biology"],"year":"2021","_id":"9283","oa_version":"Published Version"},{"oa":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","isi":1,"file":[{"file_id":"11364","file_size":2566504,"relation":"main_file","content_type":"application/pdf","creator":"dernst","date_created":"2022-05-12T12:13:27Z","access_level":"open_access","file_name":"2021_TheoreticalComputerScience_Petrov.pdf","date_updated":"2022-05-12T12:13:27Z","success":1,"checksum":"d3aef34cfb13e53bba4cf44d01680793"}],"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","author":[{"first_name":"Tatjana","full_name":"Petrov, Tatjana","last_name":"Petrov"},{"full_name":"Igler, Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87","first_name":"Claudia","last_name":"Igler"},{"last_name":"Sezgin","full_name":"Sezgin, Ali","id":"4C7638DA-F248-11E8-B48F-1D18A9856A87","first_name":"Ali"},{"last_name":"Henzinger","orcid":"0000-0002-2985-7724","full_name":"Henzinger, Thomas A","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","first_name":"Thomas A"},{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"}],"article_type":"original","publication_status":"published","project":[{"name":"Formal methods for the design and analysis of complex systems","call_identifier":"FWF","grant_number":"Z211","_id":"25F42A32-B435-11E9-9278-68D0E5697425"}],"ddc":["004"],"acknowledgement":"Tatjana Petrov’s research was supported in part by SNSF Advanced Postdoctoral Mobility Fellowship grant number P300P2 161067, the Ministry of Science, Research and the Arts of the state of Baden-Wurttemberg, and the DFG Centre of Excellence 2117 ‘Centre for the Advanced Study of Collective Behaviour’ (ID: 422037984). Claudia Igler is the recipient of a DOC Fellowship of the Austrian Academy of Sciences. Thomas A. Henzinger’s research was supported in part by the Austrian Science Fund (FWF) under grant Z211-N23 (Wittgenstein Award).","status":"public","abstract":[{"text":"Gene expression is regulated by the set of transcription factors (TFs) that bind to the promoter. The ensuing regulating function is often represented as a combinational logic circuit, where output (gene expression) is determined by current input values (promoter bound TFs) only. However, the simultaneous arrival of TFs is a strong assumption, since transcription and translation of genes introduce intrinsic time delays and there is no global synchronisation among the arrival times of different molecular species at their targets. We present an experimentally implementable genetic circuit with two inputs and one output, which in the presence of small delays in input arrival, exhibits qualitatively distinct population-level phenotypes, over timescales that are longer than typical cell doubling times. From a dynamical systems point of view, these phenotypes represent long-lived transients: although they converge to the same value eventually, they do so after a very long time span. The key feature of this toy model genetic circuit is that, despite having only two inputs and one output, it is regulated by twenty-three distinct DNA-TF configurations, two of which are more stable than others (DNA looped states), one promoting and another blocking the expression of the output gene. Small delays in input arrival time result in a majority of cells in the population quickly reaching the stable state associated with the first input, while exiting of this stable state occurs at a slow timescale. In order to mechanistically model the behaviour of this genetic circuit, we used a rule-based modelling language, and implemented a grid-search to find parameter combinations giving rise to long-lived transients. Our analysis shows that in the absence of feedback, there exist path-dependent gene regulatory mechanisms based on the long timescale of transients. The behaviour of this toy model circuit suggests that gene regulatory networks can exploit event timing to create phenotypes, and it opens the possibility that they could use event timing to memorise events, without regulatory feedback. The model reveals the importance of (i) mechanistically modelling the transitions between the different DNA-TF states, and (ii) employing transient analysis thereof.","lang":"eng"}],"date_published":"2021-06-04T00:00:00Z","scopus_import":"1","month":"06","article_processing_charge":"No","title":"Long lived transients in gene regulation","oa_version":"Published Version","_id":"9647","year":"2021","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"department":[{"_id":"ToHe"},{"_id":"CaGu"}],"file_date_updated":"2022-05-12T12:13:27Z","date_created":"2021-07-11T22:01:18Z","corr_author":"1","external_id":{"isi":["000710180500002"]},"has_accepted_license":"1","date_updated":"2025-04-15T06:25:56Z","publication_identifier":{"issn":["0304-3975"]},"quality_controlled":"1","language":[{"iso":"eng"}],"intvolume":"       893","publication":"Theoretical Computer Science","type":"journal_article","day":"04","doi":"10.1016/j.tcs.2021.05.023","publisher":"Elsevier","page":"1-16","volume":893,"citation":{"chicago":"Petrov, Tatjana, Claudia Igler, Ali Sezgin, Thomas A Henzinger, and Calin C Guet. “Long Lived Transients in Gene Regulation.” <i>Theoretical Computer Science</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.tcs.2021.05.023\">https://doi.org/10.1016/j.tcs.2021.05.023</a>.","ama":"Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. Long lived transients in gene regulation. <i>Theoretical Computer Science</i>. 2021;893:1-16. doi:<a href=\"https://doi.org/10.1016/j.tcs.2021.05.023\">10.1016/j.tcs.2021.05.023</a>","apa":"Petrov, T., Igler, C., Sezgin, A., Henzinger, T. A., &#38; Guet, C. C. (2021). Long lived transients in gene regulation. <i>Theoretical Computer Science</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.tcs.2021.05.023\">https://doi.org/10.1016/j.tcs.2021.05.023</a>","ista":"Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. 2021. Long lived transients in gene regulation. Theoretical Computer Science. 893, 1–16.","mla":"Petrov, Tatjana, et al. “Long Lived Transients in Gene Regulation.” <i>Theoretical Computer Science</i>, vol. 893, Elsevier, 2021, pp. 1–16, doi:<a href=\"https://doi.org/10.1016/j.tcs.2021.05.023\">10.1016/j.tcs.2021.05.023</a>.","ieee":"T. Petrov, C. Igler, A. Sezgin, T. A. Henzinger, and C. C. Guet, “Long lived transients in gene regulation,” <i>Theoretical Computer Science</i>, vol. 893. Elsevier, pp. 1–16, 2021.","short":"T. Petrov, C. Igler, A. Sezgin, T.A. Henzinger, C.C. Guet, Theoretical Computer Science 893 (2021) 1–16."}},{"publication":"ACS Applied Materials and Interfaces","volume":13,"citation":{"short":"T. Zisis, J. Schwarz, M. Balles, M. Kretschmer, M. Nemethova, R.P. Chait, R. Hauschild, J. Lange, C.C. Guet, M.K. Sixt, S. Zahler, ACS Applied Materials and Interfaces 13 (2021) 35545–35560.","apa":"Zisis, T., Schwarz, J., Balles, M., Kretschmer, M., Nemethova, M., Chait, R. P., … Zahler, S. (2021). Sequential and switchable patterning for studying cellular processes under spatiotemporal control. <i>ACS Applied Materials and Interfaces</i>. American Chemical Society. <a href=\"https://doi.org/10.1021/acsami.1c09850\">https://doi.org/10.1021/acsami.1c09850</a>","mla":"Zisis, Themistoklis, et al. “Sequential and Switchable Patterning for Studying Cellular Processes under Spatiotemporal Control.” <i>ACS Applied Materials and Interfaces</i>, vol. 13, no. 30, American Chemical Society, 2021, pp. 35545–35560, doi:<a href=\"https://doi.org/10.1021/acsami.1c09850\">10.1021/acsami.1c09850</a>.","ista":"Zisis T, Schwarz J, Balles M, Kretschmer M, Nemethova M, Chait RP, Hauschild R, Lange J, Guet CC, Sixt MK, Zahler S. 2021. Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. 13(30), 35545–35560.","ieee":"T. Zisis <i>et al.</i>, “Sequential and switchable patterning for studying cellular processes under spatiotemporal control,” <i>ACS Applied Materials and Interfaces</i>, vol. 13, no. 30. American Chemical Society, pp. 35545–35560, 2021.","ama":"Zisis T, Schwarz J, Balles M, et al. Sequential and switchable patterning for studying cellular processes under spatiotemporal control. <i>ACS Applied Materials and Interfaces</i>. 2021;13(30):35545–35560. doi:<a href=\"https://doi.org/10.1021/acsami.1c09850\">10.1021/acsami.1c09850</a>","chicago":"Zisis, Themistoklis, Jan Schwarz, Miriam Balles, Maibritt Kretschmer, Maria Nemethova, Remy P Chait, Robert Hauschild, et al. “Sequential and Switchable Patterning for Studying Cellular Processes under Spatiotemporal Control.” <i>ACS Applied Materials and Interfaces</i>. American Chemical Society, 2021. <a href=\"https://doi.org/10.1021/acsami.1c09850\">https://doi.org/10.1021/acsami.1c09850</a>."},"type":"journal_article","ec_funded":1,"doi":"10.1021/acsami.1c09850","day":"04","publisher":"American Chemical Society","page":"35545–35560","department":[{"_id":"MiSi"},{"_id":"GaTk"},{"_id":"Bio"},{"_id":"CaGu"}],"date_created":"2021-08-08T22:01:28Z","file_date_updated":"2021-08-09T09:44:03Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"publication_identifier":{"eissn":["1944-8252"],"issn":["1944-8244"]},"language":[{"iso":"eng"}],"quality_controlled":"1","intvolume":"        13","corr_author":"1","external_id":{"pmid":["34283577"],"isi":["000683741400026"]},"has_accepted_license":"1","date_updated":"2025-07-10T12:02:02Z","article_processing_charge":"Yes (in subscription journal)","month":"08","pmid":1,"oa_version":"Published Version","_id":"9822","issue":"30","year":"2021","title":"Sequential and switchable patterning for studying cellular processes under spatiotemporal control","author":[{"full_name":"Zisis, Themistoklis","first_name":"Themistoklis","last_name":"Zisis"},{"last_name":"Schwarz","first_name":"Jan","full_name":"Schwarz, Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Balles","full_name":"Balles, Miriam","first_name":"Miriam"},{"last_name":"Kretschmer","first_name":"Maibritt","full_name":"Kretschmer, Maibritt"},{"full_name":"Nemethova, Maria","id":"34E27F1C-F248-11E8-B48F-1D18A9856A87","first_name":"Maria","last_name":"Nemethova"},{"orcid":"0000-0003-0876-3187","last_name":"Chait","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","full_name":"Chait, Remy P","first_name":"Remy P"},{"orcid":"0000-0001-9843-3522","last_name":"Hauschild","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert"},{"full_name":"Lange, Janina","first_name":"Janina","last_name":"Lange"},{"last_name":"Guet","orcid":"0000-0001-6220-2052","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"},{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-4561-241X"},{"first_name":"Stefan","full_name":"Zahler, Stefan","last_name":"Zahler"}],"article_type":"original","publication_status":"published","project":[{"call_identifier":"H2020","name":"Cellular Navigation Along Spatial Gradients","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425"}],"oa":1,"isi":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"date_updated":"2021-08-09T09:44:03Z","file_name":"2021_ACSAppliedMaterialsAndInterfaces_Zisis.pdf","success":1,"checksum":"b043a91d9f9200e467b970b692687ed3","file_id":"9833","file_size":7123293,"relation":"main_file","content_type":"application/pdf","access_level":"open_access","date_created":"2021-08-09T09:44:03Z","creator":"asandaue"}],"status":"public","date_published":"2021-08-04T00:00:00Z","abstract":[{"lang":"eng","text":"Attachment of adhesive molecules on cell culture surfaces to restrict cell adhesion to defined areas and shapes has been vital for the progress of in vitro research. In currently existing patterning methods, a combination of pattern properties such as stability, precision, specificity, high-throughput outcome, and spatiotemporal control is highly desirable but challenging to achieve. Here, we introduce a versatile and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent patterning step and a subsequent functionalization of the pattern via click chemistry. This two-step process is feasible on arbitrary surfaces and allows for generation of sustainable patterns and gradients. The method is validated in different biological systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining the growth and migration of cells to the designated areas. We then implement a sequential photopatterning approach by adding a second switchable patterning step, allowing for spatiotemporal control over two distinct surface patterns. As a proof of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis. Our results show that the spatiotemporal control provided by our “sequential photopatterning” system is essential for mimicking dynamic biological processes and that our innovative approach has great potential for further applications in cell science."}],"scopus_import":"1","ddc":["620","570"],"acknowledgement":"We would like to thank Charlott Leu for the production of our chromium wafers, Louise Ritter for her contribution of the IF stainings in Figure 4, Shokoufeh Teymouri for her help with the Bioinert coated slides, and finally Prof. Dr. Joachim Rädler for his valuable scientific guidance."},{"day":"18","publisher":"Cold Spring Harbor Laboratory","doi":"10.1101/2021.10.18.464770","title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","related_material":{"record":[{"id":"11843","relation":"later_version","status":"public"},{"id":"10307","relation":"dissertation_contains","status":"public"}]},"ec_funded":1,"type":"preprint","year":"2021","citation":{"ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>","chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2021.10.18.464770\">https://doi.org/10.1101/2021.10.18.464770</a>.","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, BioRxiv (n.d.).","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. bioRxiv, <a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>.","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (n.d.). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2021.10.18.464770\">https://doi.org/10.1101/2021.10.18.464770</a>","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2021.10.18.464770\">10.1101/2021.10.18.464770</a>.","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory."},"_id":"10316","oa_version":"Preprint","main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1"}],"month":"10","publication":"bioRxiv","article_processing_charge":"No","date_updated":"2026-05-04T22:30:43Z","acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strain CFT073, Vlad Gavra and Maximilian Götz, Bor Kavčič, Jonna Alanko and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to I.G., the European Research Council (CoG 724373) and the Austrian Science Fund (FWF P29911) to M.S.","corr_author":"1","abstract":[{"lang":"eng","text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease."}],"date_published":"2021-10-18T00:00:00Z","language":[{"iso":"eng"}],"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"oa":1,"project":[{"grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425","name":"Cellular Navigation Along Spatial Gradients","call_identifier":"H2020"},{"_id":"26018E70-B435-11E9-9278-68D0E5697425","grant_number":"P29911","call_identifier":"FWF","name":"Mechanical adaptation of lamellipodial actin"}],"publication_status":"draft","date_created":"2021-11-19T12:24:16Z","author":[{"last_name":"Tomasek","orcid":"0000-0003-3768-877X","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","full_name":"Tomasek, Kathrin","first_name":"Kathrin"},{"last_name":"Leithner","orcid":"0000-0002-1073-744X","first_name":"Alexander F","full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Glatzová, Ivana","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d","first_name":"Ivana","last_name":"Glatzová"},{"last_name":"Lukesch","full_name":"Lukesch, Michael S.","first_name":"Michael S."},{"last_name":"Guet","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","first_name":"Calin C"},{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","last_name":"Sixt","orcid":"0000-0002-4561-241X"}],"department":[{"_id":"CaGu"},{"_id":"MiSi"}]},{"title":"Gene amplification as a form of population-level gene expression regulation","oa_version":"Submitted Version","issue":"4","_id":"7652","year":"2020","month":"04","pmid":1,"article_processing_charge":"No","ddc":["570"],"acknowledgement":"We thank L. Hurst, N. Barton, M. Pleska, M. Steinrück, B. Kavcic and A. Staron for input on the manuscript, and To. Bergmiller and R. Chait for help with microfluidics experiments. I.T. is a recipient the OMV fellowship. R.G. is a recipient of a DOC (Doctoral Fellowship Programme of the Austrian Academy of Sciences) Fellowship of the Austrian Academy of Sciences.","status":"public","abstract":[{"text":"Organisms cope with change by taking advantage of transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. Here, we investigate whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using real-time monitoring of gene-copy-number mutations in Escherichia coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy-number and, therefore, expression-level polymorphisms. This amplification-mediated gene expression tuning (AMGET) occurs on timescales that are similar to canonical gene regulation and can respond to rapid environmental changes. Mathematical modelling shows that amplifications also tune gene expression in stochastic environments in which transcription-factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune the expression of any gene, without leaving any genomic signature.","lang":"eng"}],"date_published":"2020-04-01T00:00:00Z","scopus_import":"1","oa":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","isi":1,"file":[{"file_name":"2020_NatureEcolEvo_Tomanek.pdf","date_updated":"2020-10-09T09:56:01Z","success":1,"checksum":"ef3bbf42023e30b2c24a6278025d2040","file_id":"8640","relation":"main_file","file_size":745242,"content_type":"application/pdf","creator":"dernst","date_created":"2020-10-09T09:56:01Z","access_level":"open_access"}],"author":[{"id":"3981F020-F248-11E8-B48F-1D18A9856A87","full_name":"Tomanek, Isabella","first_name":"Isabella","orcid":"0000-0001-6197-363X","last_name":"Tomanek"},{"full_name":"Grah, Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","first_name":"Rok","orcid":"0000-0003-2539-3560","last_name":"Grah"},{"last_name":"Lagator","full_name":"Lagator, M.","first_name":"M."},{"full_name":"Andersson, A. M. C.","first_name":"A. M. C.","last_name":"Andersson"},{"full_name":"Bollback, Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","first_name":"Jonathan P","orcid":"0000-0002-4624-4612","last_name":"Bollback"},{"orcid":"0000-0002-6699-1455","last_name":"Tkačik","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper"},{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"}],"publication_status":"published","article_type":"original","project":[{"name":"Biophysically realistic genotype-phenotype maps for regulatory networks","_id":"267C84F4-B435-11E9-9278-68D0E5697425"}],"type":"journal_article","related_material":{"link":[{"url":"https://ist.ac.at/en/news/how-to-thrive-without-gene-regulation/","description":"News on IST Homepage","relation":"press_release"}],"record":[{"status":"public","relation":"research_data","id":"7016"},{"status":"public","relation":"research_data","id":"7383"},{"id":"8155","relation":"dissertation_contains","status":"public"},{"status":"public","id":"8653","relation":"used_in_publication"}]},"doi":"10.1038/s41559-020-1132-7","publisher":"Springer Nature","day":"01","page":"612-625","volume":4,"citation":{"chicago":"Tomanek, Isabella, Rok Grah, M. Lagator, A. M. C. Andersson, Jonathan P Bollback, Gašper Tkačik, and Calin C Guet. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” <i>Nature Ecology &#38; Evolution</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41559-020-1132-7\">https://doi.org/10.1038/s41559-020-1132-7</a>.","ama":"Tomanek I, Grah R, Lagator M, et al. Gene amplification as a form of population-level gene expression regulation. <i>Nature Ecology &#38; Evolution</i>. 2020;4(4):612-625. doi:<a href=\"https://doi.org/10.1038/s41559-020-1132-7\">10.1038/s41559-020-1132-7</a>","ista":"Tomanek I, Grah R, Lagator M, Andersson AMC, Bollback JP, Tkačik G, Guet CC. 2020. Gene amplification as a form of population-level gene expression regulation. Nature Ecology &#38; Evolution. 4(4), 612–625.","mla":"Tomanek, Isabella, et al. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” <i>Nature Ecology &#38; Evolution</i>, vol. 4, no. 4, Springer Nature, 2020, pp. 612–25, doi:<a href=\"https://doi.org/10.1038/s41559-020-1132-7\">10.1038/s41559-020-1132-7</a>.","apa":"Tomanek, I., Grah, R., Lagator, M., Andersson, A. M. C., Bollback, J. P., Tkačik, G., &#38; Guet, C. C. (2020). Gene amplification as a form of population-level gene expression regulation. <i>Nature Ecology &#38; Evolution</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41559-020-1132-7\">https://doi.org/10.1038/s41559-020-1132-7</a>","ieee":"I. Tomanek <i>et al.</i>, “Gene amplification as a form of population-level gene expression regulation,” <i>Nature Ecology &#38; Evolution</i>, vol. 4, no. 4. Springer Nature, pp. 612–625, 2020.","short":"I. Tomanek, R. Grah, M. Lagator, A.M.C. Andersson, J.P. Bollback, G. Tkačik, C.C. Guet, Nature Ecology &#38; Evolution 4 (2020) 612–625."},"publication":"Nature Ecology & Evolution","external_id":{"pmid":["32152532"],"isi":["000519008300005"]},"has_accepted_license":"1","date_updated":"2026-05-04T22:30:50Z","publication_identifier":{"issn":["2397-334X"]},"quality_controlled":"1","language":[{"iso":"eng"}],"intvolume":"         4","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"date_created":"2020-04-08T15:20:53Z","file_date_updated":"2020-10-09T09:56:01Z"},{"date_published":"2019-07-02T00:00:00Z","status":"public","date_updated":"2025-04-15T07:33:55Z","date_created":"2021-08-06T08:23:43Z","author":[{"first_name":"Jakob","full_name":"Ruess, Jakob","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1615-3282","last_name":"Ruess"},{"last_name":"Pleska","orcid":"0000-0001-7460-7479","first_name":"Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87","full_name":"Pleska, Maros"},{"orcid":"0000-0001-6220-2052","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","first_name":"Calin C"},{"orcid":"0000-0002-6699-1455","last_name":"Tkačik","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper"}],"department":[{"_id":"CaGu"},{"_id":"GaTk"}],"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","year":"2019","_id":"9786","citation":{"chicago":"Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Supporting Text and Results.” Public Library of Science, 2019. <a href=\"https://doi.org/10.1371/journal.pcbi.1007168.s001\">https://doi.org/10.1371/journal.pcbi.1007168.s001</a>.","ama":"Ruess J, Pleska M, Guet CC, Tkačik G. Supporting text and results. 2019. doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007168.s001\">10.1371/journal.pcbi.1007168.s001</a>","ista":"Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Supporting text and results, Public Library of Science, <a href=\"https://doi.org/10.1371/journal.pcbi.1007168.s001\">10.1371/journal.pcbi.1007168.s001</a>.","apa":"Ruess, J., Pleska, M., Guet, C. C., &#38; Tkačik, G. (2019). Supporting text and results. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1007168.s001\">https://doi.org/10.1371/journal.pcbi.1007168.s001</a>","mla":"Ruess, Jakob, et al. <i>Supporting Text and Results</i>. Public Library of Science, 2019, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007168.s001\">10.1371/journal.pcbi.1007168.s001</a>.","ieee":"J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Supporting text and results.” Public Library of Science, 2019.","short":"J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, (2019)."},"oa_version":"Published Version","publisher":"Public Library of Science","doi":"10.1371/journal.pcbi.1007168.s001","day":"02","title":"Supporting text and results","related_material":{"record":[{"relation":"used_in_publication","id":"6784","status":"public"}]},"type":"research_data_reference","article_processing_charge":"No","month":"07"},{"day":"02","doi":"10.1371/journal.pcbi.1007168","publisher":"Public Library of Science","type":"journal_article","related_material":{"record":[{"status":"public","id":"9786","relation":"research_data"}]},"citation":{"chicago":"Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” <i>PLoS Computational Biology</i>. Public Library of Science, 2019. <a href=\"https://doi.org/10.1371/journal.pcbi.1007168\">https://doi.org/10.1371/journal.pcbi.1007168</a>.","ama":"Ruess J, Pleska M, Guet CC, Tkačik G. Molecular noise of innate immunity shapes bacteria-phage ecologies. <i>PLoS Computational Biology</i>. 2019;15(7). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007168\">10.1371/journal.pcbi.1007168</a>","ieee":"J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Molecular noise of innate immunity shapes bacteria-phage ecologies,” <i>PLoS Computational Biology</i>, vol. 15, no. 7. Public Library of Science, 2019.","mla":"Ruess, Jakob, et al. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” <i>PLoS Computational Biology</i>, vol. 15, no. 7, e1007168, Public Library of Science, 2019, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007168\">10.1371/journal.pcbi.1007168</a>.","ista":"Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Molecular noise of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology. 15(7), e1007168.","apa":"Ruess, J., Pleska, M., Guet, C. C., &#38; Tkačik, G. (2019). Molecular noise of innate immunity shapes bacteria-phage ecologies. <i>PLoS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1007168\">https://doi.org/10.1371/journal.pcbi.1007168</a>","short":"J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, PLoS Computational Biology 15 (2019)."},"volume":15,"publication":"PLoS Computational Biology","has_accepted_license":"1","date_updated":"2025-04-14T13:46:26Z","external_id":{"isi":["000481577700032"]},"language":[{"iso":"eng"}],"quality_controlled":"1","intvolume":"        15","publication_identifier":{"eissn":["1553-7358"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"date_created":"2019-08-11T21:59:19Z","file_date_updated":"2020-07-14T12:47:40Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"article_number":"e1007168","title":"Molecular noise of innate immunity shapes bacteria-phage ecologies","_id":"6784","issue":"7","year":"2019","oa_version":"Published Version","month":"07","article_processing_charge":"No","ddc":["570"],"date_published":"2019-07-02T00:00:00Z","scopus_import":"1","abstract":[{"text":"Mathematical models have been used successfully at diverse scales of biological organization, ranging from ecology and population dynamics to stochastic reaction events occurring between individual molecules in single cells. Generally, many biological processes unfold across multiple scales, with mutations being the best studied example of how stochasticity at the molecular scale can influence outcomes at the population scale. In many other contexts, however, an analogous link between micro- and macro-scale remains elusive, primarily due to the challenges involved in setting up and analyzing multi-scale models. Here, we employ such a model to investigate how stochasticity propagates from individual biochemical reaction events in the bacterial innate immune system to the ecology of bacteria and bacterial viruses. We show analytically how the dynamics of bacterial populations are shaped by the activities of immunity-conferring enzymes in single cells and how the ecological consequences imply optimal bacterial defense strategies against viruses. Our results suggest that bacterial populations in the presence of viruses can either optimize their initial growth rate or their population size, with the first strategy favoring simple immunity featuring a single restriction modification system and the second strategy favoring complex bacterial innate immunity featuring several simultaneously active restriction modification systems.","lang":"eng"}],"status":"public","isi":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"checksum":"7ded4721b41c2a0fc66a1c634540416a","date_updated":"2020-07-14T12:47:40Z","file_name":"2019_PlosComputBiology_Ruess.pdf","content_type":"application/pdf","access_level":"open_access","date_created":"2019-08-12T12:27:26Z","creator":"dernst","file_id":"6803","relation":"main_file","file_size":2200003}],"oa":1,"publication_status":"published","article_type":"original","project":[{"grant_number":"24210","_id":"251D65D8-B435-11E9-9278-68D0E5697425","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level"},{"_id":"251BCBEC-B435-11E9-9278-68D0E5697425","grant_number":"RGY0079/2011","name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems"}],"author":[{"orcid":"0000-0003-1615-3282","last_name":"Ruess","full_name":"Ruess, Jakob","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","first_name":"Jakob"},{"orcid":"0000-0001-7460-7479","last_name":"Pleska","first_name":"Maros","full_name":"Pleska, Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"},{"full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","orcid":"0000-0002-6699-1455","last_name":"Tkačik"}]},{"department":[{"_id":"CaGu"},{"_id":"ToHe"}],"date_created":"2019-12-04T16:07:50Z","publication_identifier":{"isbn":["9783030313036"],"eisbn":["9783030313043"],"issn":["0302-9743"],"eissn":["1611-3349"]},"quality_controlled":"1","language":[{"iso":"eng"}],"intvolume":"     11773","external_id":{"isi":["000557875100009"]},"date_updated":"2026-04-16T10:26:49Z","publication":"17th International Conference on Computational Methods in Systems Biology","volume":11773,"citation":{"chicago":"Guet, Calin C, Thomas A Henzinger, Claudia Igler, Tatjana Petrov, and Ali Sezgin. “Transient Memory in Gene Regulation.” In <i>17th International Conference on Computational Methods in Systems Biology</i>, 11773:155–87. Springer Nature, 2019. <a href=\"https://doi.org/10.1007/978-3-030-31304-3_9\">https://doi.org/10.1007/978-3-030-31304-3_9</a>.","ama":"Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. Transient memory in gene regulation. In: <i>17th International Conference on Computational Methods in Systems Biology</i>. Vol 11773. Springer Nature; 2019:155-187. doi:<a href=\"https://doi.org/10.1007/978-3-030-31304-3_9\">10.1007/978-3-030-31304-3_9</a>","ieee":"C. C. Guet, T. A. Henzinger, C. Igler, T. Petrov, and A. Sezgin, “Transient memory in gene regulation,” in <i>17th International Conference on Computational Methods in Systems Biology</i>, Trieste, Italy, 2019, vol. 11773, pp. 155–187.","apa":"Guet, C. C., Henzinger, T. A., Igler, C., Petrov, T., &#38; Sezgin, A. (2019). Transient memory in gene regulation. In <i>17th International Conference on Computational Methods in Systems Biology</i> (Vol. 11773, pp. 155–187). Trieste, Italy: Springer Nature. <a href=\"https://doi.org/10.1007/978-3-030-31304-3_9\">https://doi.org/10.1007/978-3-030-31304-3_9</a>","mla":"Guet, Calin C., et al. “Transient Memory in Gene Regulation.” <i>17th International Conference on Computational Methods in Systems Biology</i>, vol. 11773, Springer Nature, 2019, pp. 155–87, doi:<a href=\"https://doi.org/10.1007/978-3-030-31304-3_9\">10.1007/978-3-030-31304-3_9</a>.","ista":"Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. 2019. Transient memory in gene regulation. 17th International Conference on Computational Methods in Systems Biology. CMSB: Computational Methods in Systems Biology, LNCS, vol. 11773, 155–187.","short":"C.C. Guet, T.A. Henzinger, C. Igler, T. Petrov, A. Sezgin, in:, 17th International Conference on Computational Methods in Systems Biology, Springer Nature, 2019, pp. 155–187."},"type":"conference","doi":"10.1007/978-3-030-31304-3_9","publisher":"Springer Nature","day":"17","page":"155-187","author":[{"last_name":"Guet","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"},{"id":"40876CD8-F248-11E8-B48F-1D18A9856A87","full_name":"Henzinger, Thomas A","first_name":"Thomas A","orcid":"0000−0002−2985−7724","last_name":"Henzinger"},{"first_name":"Claudia","full_name":"Igler, Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87","last_name":"Igler","orcid":"0000-0001-7777-546X"},{"last_name":"Petrov","orcid":"0000-0002-9041-0905","first_name":"Tatjana","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","full_name":"Petrov, Tatjana"},{"full_name":"Sezgin, Ali","id":"4C7638DA-F248-11E8-B48F-1D18A9856A87","first_name":"Ali","last_name":"Sezgin"}],"publication_status":"published","project":[{"grant_number":"Z211","_id":"25F42A32-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Formal methods for the design and analysis of complex systems"},{"name":"Design principles underlying genetic switch architecture","_id":"251EE76E-B435-11E9-9278-68D0E5697425","grant_number":"24573"}],"isi":1,"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","status":"public","date_published":"2019-09-17T00:00:00Z","abstract":[{"text":"The expression of a gene is characterised by its transcription factors and the function processing them. If the transcription factors are not affected by gene products, the regulating function is often represented as a combinational logic circuit, where the outputs (product) are determined by current input values (transcription factors) only, and are hence independent on their relative arrival times. However, the simultaneous arrival of transcription factors (TFs) in genetic circuits is a strong assumption, given that the processes of transcription and translation of a gene into a protein introduce intrinsic time delays and that there is no global synchronisation among the arrival times of different molecular species at molecular targets.\r\n\r\nIn this paper, we construct an experimentally implementable genetic circuit with two inputs and a single output, such that, in presence of small delays in input arrival, the circuit exhibits qualitatively distinct observable phenotypes. In particular, these phenotypes are long lived transients: they all converge to a single value, but so slowly, that they seem stable for an extended time period, longer than typical experiment duration. We used rule-based language to prototype our circuit, and we implemented a search for finding the parameter combinations raising the phenotypes of interest.\r\n\r\nThe behaviour of our prototype circuit has wide implications. First, it suggests that GRNs can exploit event timing to create phenotypes. Second, it opens the possibility that GRNs are using event timing to react to stimuli and memorise events, without explicit feedback in regulation. From the modelling perspective, our prototype circuit demonstrates the critical importance of analysing the transient dynamics at the promoter binding sites of the DNA, before applying rapid equilibrium assumptions.","lang":"eng"}],"scopus_import":"1","conference":{"location":"Trieste, Italy","name":"CMSB: Computational Methods in Systems Biology","end_date":"2019-09-20","start_date":"2019-09-18"},"alternative_title":["LNCS"],"article_processing_charge":"No","month":"09","oa_version":"None","_id":"7147","year":"2019","title":"Transient memory in gene regulation"},{"status":"public","abstract":[{"lang":"eng","text":"Which properties of metabolic networks can be derived solely from stoichiometry? Predictive results have been obtained by flux balance analysis (FBA), by postulating that cells set metabolic fluxes to maximize growth rate. Here we consider a generalization of FBA to single-cell level using maximum entropy modeling, which we extend and test experimentally. Specifically, we define for Escherichia coli metabolism a flux distribution that yields the experimental growth rate: the model, containing FBA as a limit, provides a better match to measured fluxes and it makes a wide range of predictions: on flux variability, regulation, and correlations; on the relative importance of stoichiometry vs. optimization; on scaling relations for growth rate distributions. We validate the latter here with single-cell data at different sub-inhibitory antibiotic concentrations. The model quantifies growth optimization as emerging from the interplay of competitive dynamics in the population and regulation of metabolism at the level of single cells."}],"scopus_import":"1","date_published":"2018-07-30T00:00:00Z","ddc":["570"],"author":[{"last_name":"De Martino","orcid":"0000-0002-5214-4706","first_name":"Daniele","full_name":"De Martino, Daniele","id":"3FF5848A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Mc","first_name":"Andersson Anna","full_name":"Mc, Andersson Anna"},{"first_name":"Tobias","full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","last_name":"Bergmiller","orcid":"0000-0001-5396-4346"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","first_name":"Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"},{"last_name":"Tkacik","orcid":"0000-0002-6699-1455","first_name":"Gasper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkacik, Gasper"}],"publication_status":"published","project":[{"call_identifier":"FWF","name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27","_id":"254E9036-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"}],"oa":1,"isi":1,"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","file":[{"date_created":"2018-12-17T16:44:28Z","creator":"dernst","access_level":"open_access","content_type":"application/pdf","relation":"main_file","file_size":1043205,"file_id":"5728","checksum":"3ba7ab27b27723c7dcf633e8fc1f8f18","file_name":"2018_NatureComm_DeMartino.pdf","date_updated":"2020-07-14T12:45:06Z"}],"oa_version":"Published Version","_id":"161","issue":"1","year":"2018","title":"Statistical mechanics for metabolic networks during steady state growth","article_processing_charge":"No","month":"07","language":[{"iso":"eng"}],"quality_controlled":"1","intvolume":"         9","external_id":{"isi":["000440149300021"]},"has_accepted_license":"1","date_updated":"2025-04-15T06:50:08Z","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"article_number":"2988","file_date_updated":"2020-07-14T12:45:06Z","date_created":"2018-12-11T11:44:57Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"volume":9,"citation":{"apa":"De Martino, D., Mc, A. A., Bergmiller, T., Guet, C. C., &#38; Tkačik, G. (2018). Statistical mechanics for metabolic networks during steady state growth. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-018-05417-9\">https://doi.org/10.1038/s41467-018-05417-9</a>","mla":"De Martino, Daniele, et al. “Statistical Mechanics for Metabolic Networks during Steady State Growth.” <i>Nature Communications</i>, vol. 9, no. 1, 2988, Springer Nature, 2018, doi:<a href=\"https://doi.org/10.1038/s41467-018-05417-9\">10.1038/s41467-018-05417-9</a>.","ista":"De Martino D, Mc AA, Bergmiller T, Guet CC, Tkačik G. 2018. Statistical mechanics for metabolic networks during steady state growth. Nature Communications. 9(1), 2988.","ieee":"D. De Martino, A. A. Mc, T. Bergmiller, C. C. Guet, and G. Tkačik, “Statistical mechanics for metabolic networks during steady state growth,” <i>Nature Communications</i>, vol. 9, no. 1. Springer Nature, 2018.","short":"D. De Martino, A.A. Mc, T. Bergmiller, C.C. Guet, G. Tkačik, Nature Communications 9 (2018).","chicago":"De Martino, Daniele, Andersson Anna Mc, Tobias Bergmiller, Calin C Guet, and Gašper Tkačik. “Statistical Mechanics for Metabolic Networks during Steady State Growth.” <i>Nature Communications</i>. Springer Nature, 2018. <a href=\"https://doi.org/10.1038/s41467-018-05417-9\">https://doi.org/10.1038/s41467-018-05417-9</a>.","ama":"De Martino D, Mc AA, Bergmiller T, Guet CC, Tkačik G. Statistical mechanics for metabolic networks during steady state growth. <i>Nature Communications</i>. 2018;9(1). doi:<a href=\"https://doi.org/10.1038/s41467-018-05417-9\">10.1038/s41467-018-05417-9</a>"},"ec_funded":1,"type":"journal_article","related_material":{"record":[{"status":"public","relation":"popular_science","id":"5587"}]},"day":"30","publisher":"Springer Nature","doi":"10.1038/s41467-018-05417-9","publication":"Nature Communications","publist_id":"7760"},{"publist_id":"7972","publication":"PLoS Biology","related_material":{"record":[{"id":"9810","relation":"research_data","status":"public"}]},"type":"journal_article","doi":"10.1371/journal.pbio.2005971","day":"16","publisher":"Public Library of Science","volume":16,"citation":{"short":"W. Chaudhry, M. Pleska, N. Shah, H. Weiss, I. Mccall, J. Meyer, A. Gupta, C.C. Guet, B. Levin, PLoS Biology 16 (2018).","apa":"Chaudhry, W., Pleska, M., Shah, N., Weiss, H., Mccall, I., Meyer, J., … Levin, B. (2018). Leaky resistance and the conditions for the existence of lytic bacteriophage. <i>PLoS Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pbio.2005971\">https://doi.org/10.1371/journal.pbio.2005971</a>","ista":"Chaudhry W, Pleska M, Shah N, Weiss H, Mccall I, Meyer J, Gupta A, Guet CC, Levin B. 2018. Leaky resistance and the conditions for the existence of lytic bacteriophage. PLoS Biology. 16(8), 2005971.","mla":"Chaudhry, Waqas, et al. “Leaky Resistance and the Conditions for the Existence of Lytic Bacteriophage.” <i>PLoS Biology</i>, vol. 16, no. 8, 2005971, Public Library of Science, 2018, doi:<a href=\"https://doi.org/10.1371/journal.pbio.2005971\">10.1371/journal.pbio.2005971</a>.","ieee":"W. Chaudhry <i>et al.</i>, “Leaky resistance and the conditions for the existence of lytic bacteriophage,” <i>PLoS Biology</i>, vol. 16, no. 8. Public Library of Science, 2018.","ama":"Chaudhry W, Pleska M, Shah N, et al. Leaky resistance and the conditions for the existence of lytic bacteriophage. <i>PLoS Biology</i>. 2018;16(8). doi:<a href=\"https://doi.org/10.1371/journal.pbio.2005971\">10.1371/journal.pbio.2005971</a>","chicago":"Chaudhry, Waqas, Maros Pleska, Nilang Shah, Howard Weiss, Ingrid Mccall, Justin Meyer, Animesh Gupta, Calin C Guet, and Bruce Levin. “Leaky Resistance and the Conditions for the Existence of Lytic Bacteriophage.” <i>PLoS Biology</i>. Public Library of Science, 2018. <a href=\"https://doi.org/10.1371/journal.pbio.2005971\">https://doi.org/10.1371/journal.pbio.2005971</a>."},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_number":"2005971","department":[{"_id":"CaGu"}],"file_date_updated":"2020-07-14T12:48:10Z","date_created":"2018-12-11T11:44:32Z","external_id":{"isi":["000443383300024"]},"date_updated":"2023-09-13T08:45:41Z","has_accepted_license":"1","intvolume":"        16","language":[{"iso":"eng"}],"quality_controlled":"1","month":"08","article_processing_charge":"Yes","title":"Leaky resistance and the conditions for the existence of lytic bacteriophage","oa_version":"Published Version","year":"2018","_id":"82","issue":"8","oa":1,"file":[{"content_type":"application/pdf","access_level":"open_access","creator":"dernst","date_created":"2018-12-17T12:55:31Z","file_id":"5706","file_size":4007095,"relation":"main_file","checksum":"527076f78265cd4ea192cd1569851587","date_updated":"2020-07-14T12:48:10Z","file_name":"2018_Plos_Chaudhry.pdf"}],"isi":1,"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","author":[{"first_name":"Waqas","full_name":"Chaudhry, Waqas","last_name":"Chaudhry"},{"first_name":"Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87","full_name":"Pleska, Maros","last_name":"Pleska","orcid":"0000-0001-7460-7479"},{"first_name":"Nilang","full_name":"Shah, Nilang","last_name":"Shah"},{"full_name":"Weiss, Howard","first_name":"Howard","last_name":"Weiss"},{"first_name":"Ingrid","full_name":"Mccall, Ingrid","last_name":"Mccall"},{"last_name":"Meyer","full_name":"Meyer, Justin","first_name":"Justin"},{"last_name":"Gupta","full_name":"Gupta, Animesh","first_name":"Animesh"},{"orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"},{"last_name":"Levin","first_name":"Bruce","full_name":"Levin, Bruce"}],"publication_status":"published","ddc":["570"],"status":"public","date_published":"2018-08-16T00:00:00Z","scopus_import":"1","abstract":[{"lang":"eng","text":"In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage, bacterial cells resistant to the phage commonly emerge and become the dominant population of bacteria. Following the ascent of resistant mutants, the densities of bacteria in these simple communities become limited by resources rather than the phage. Despite the evolution of resistant hosts, upon which the phage cannot replicate, the lytic phage population is most commonly maintained in an apparently stable state with the resistant bacteria. Several mechanisms have been put forward to account for this result. Here we report the results of population dynamic/evolution experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli in serial transfer cultures. We show that, following the ascent of λVIR-resistant bacteria, λVIRis maintained in the majority of cases in maltose-limited minimal media and in all cases in nutrient-rich broth. Using mathematical models and experiments, we show that the dominant mechanism responsible for maintenance of λVIRin these resource-limited populations dominated by resistant E. coli is a high rate of either phenotypic or genetic transition from resistance to susceptibility—a hitherto undemonstrated mechanism we term &quot;leaky resistance.&quot; We discuss the implications of leaky resistance to our understanding of the conditions for the maintenance of phage in populations of bacteria—their “existence conditions.”."}]},{"department":[{"_id":"CaGu"}],"author":[{"last_name":"Chaudhry","full_name":"Chaudhry, Waqas","first_name":"Waqas"},{"first_name":"Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87","full_name":"Pleska, Maros","orcid":"0000-0001-7460-7479","last_name":"Pleska"},{"first_name":"Nilang","full_name":"Shah, Nilang","last_name":"Shah"},{"full_name":"Weiss, Howard","first_name":"Howard","last_name":"Weiss"},{"last_name":"Mccall","first_name":"Ingrid","full_name":"Mccall, Ingrid"},{"last_name":"Meyer","first_name":"Justin","full_name":"Meyer, Justin"},{"last_name":"Gupta","first_name":"Animesh","full_name":"Gupta, Animesh"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052"},{"last_name":"Levin","full_name":"Levin, Bruce","first_name":"Bruce"}],"date_created":"2021-08-06T12:43:44Z","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","status":"public","date_published":"2018-08-16T00:00:00Z","date_updated":"2023-09-13T08:45:41Z","article_processing_charge":"No","month":"08","oa_version":"Published Version","_id":"9810","citation":{"ama":"Chaudhry W, Pleska M, Shah N, et al. Numerical data used in figures. 2018. doi:<a href=\"https://doi.org/10.1371/journal.pbio.2005971.s008\">10.1371/journal.pbio.2005971.s008</a>","chicago":"Chaudhry, Waqas, Maros Pleska, Nilang Shah, Howard Weiss, Ingrid Mccall, Justin Meyer, Animesh Gupta, Calin C Guet, and Bruce Levin. “Numerical Data Used in Figures.” Public Library of Science, 2018. <a href=\"https://doi.org/10.1371/journal.pbio.2005971.s008\">https://doi.org/10.1371/journal.pbio.2005971.s008</a>.","short":"W. Chaudhry, M. Pleska, N. Shah, H. Weiss, I. Mccall, J. Meyer, A. Gupta, C.C. Guet, B. Levin, (2018).","ieee":"W. Chaudhry <i>et al.</i>, “Numerical data used in figures.” Public Library of Science, 2018.","apa":"Chaudhry, W., Pleska, M., Shah, N., Weiss, H., Mccall, I., Meyer, J., … Levin, B. (2018). Numerical data used in figures. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pbio.2005971.s008\">https://doi.org/10.1371/journal.pbio.2005971.s008</a>","ista":"Chaudhry W, Pleska M, Shah N, Weiss H, Mccall I, Meyer J, Gupta A, Guet CC, Levin B. 2018. Numerical data used in figures, Public Library of Science, <a href=\"https://doi.org/10.1371/journal.pbio.2005971.s008\">10.1371/journal.pbio.2005971.s008</a>.","mla":"Chaudhry, Waqas, et al. <i>Numerical Data Used in Figures</i>. Public Library of Science, 2018, doi:<a href=\"https://doi.org/10.1371/journal.pbio.2005971.s008\">10.1371/journal.pbio.2005971.s008</a>."},"year":"2018","type":"research_data_reference","title":"Numerical data used in figures","related_material":{"record":[{"status":"public","id":"82","relation":"used_in_publication"}]},"publisher":"Public Library of Science","day":"16","doi":"10.1371/journal.pbio.2005971.s008"}]