[{"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.","year":"2023","_id":"12478","date_updated":"2023-08-02T06:25:04Z","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"}],"oa_version":"Published Version","type":"journal_article","month":"06","volume":14,"file_date_updated":"2023-07-31T07:16:34Z","date_created":"2023-02-02T08:13:28Z","status":"public","external_id":{"isi":["001030002600001"],"pmid":["37485524"]},"intvolume":"        14","citation":{"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>","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>.","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.","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>","short":"C.C. Guet, L. Bruneaux, P. Oikonomou, M. Aldana, P. Cluzel, Frontiers in Microbiology 14 (2023).","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>.","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."},"oa":1,"publication_status":"published","has_accepted_license":"1","date_published":"2023-06-20T00:00:00Z","ddc":["570"],"publisher":"Frontiers","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"department":[{"_id":"CaGu"}],"publication":"Frontiers in Microbiology","scopus_import":"1","article_processing_charge":"Yes","article_type":"original","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)"},"author":[{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"},{"last_name":"Bruneaux","first_name":"L","full_name":"Bruneaux, L"},{"full_name":"Oikonomou, P","first_name":"P","last_name":"Oikonomou"},{"full_name":"Aldana, M","last_name":"Aldana","first_name":"M"},{"full_name":"Cluzel, P","first_name":"P","last_name":"Cluzel"}],"day":"20","file":[{"file_name":"2023_FrontiersMicrobiology_Guet.pdf","success":1,"file_size":6452841,"relation":"main_file","content_type":"application/pdf","creator":"dernst","file_id":"13322","date_updated":"2023-07-31T07:16:34Z","checksum":"7dd322347512afaa5daf72a0154f2f07","date_created":"2023-07-31T07:16:34Z","access_level":"open_access"}],"title":"Monitoring lineages of growing and dividing bacteria reveals an inducible memory of <i>mar</i> operon expression","article_number":"1049255","isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1664-302X"]},"doi":"10.3389/fmicb.2023.1049255","quality_controlled":"1"},{"doi":"10.7554/eLife.64543","quality_controlled":"1","publication_identifier":{"eissn":["2050-084X"]},"isi":1,"language":[{"iso":"eng"}],"project":[{"call_identifier":"H2020","_id":"2578D616-B435-11E9-9278-68D0E5697425","name":"Selective Barriers to Horizontal Gene Transfer","grant_number":"648440"}],"article_number":"e64543","title":"Predicting bacterial promoter function and evolution from random sequences","author":[{"full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator"},{"last_name":"Sarikas","first_name":"Srdjan","id":"35F0286E-F248-11E8-B48F-1D18A9856A87","full_name":"Sarikas, Srdjan"},{"first_name":"Magdalena","last_name":"Steinrueck","full_name":"Steinrueck, Magdalena"},{"last_name":"Toledo-Aparicio","first_name":"David","full_name":"Toledo-Aparicio, David"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","first_name":"Jonathan P","last_name":"Bollback"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"},{"first_name":"Gašper","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper"}],"day":"26","file":[{"date_created":"2022-02-07T07:14:09Z","access_level":"open_access","date_updated":"2022-02-07T07:14:09Z","file_id":"10739","checksum":"decdcdf600ff51e9a9703b49ca114170","relation":"main_file","content_type":"application/pdf","file_size":5604343,"creator":"cchlebak","success":1,"file_name":"2022_ELife_Lagator.pdf"}],"publication":"eLife","article_type":"original","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)"},"scopus_import":"1","ec_funded":1,"article_processing_charge":"No","publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"NiBa"}],"pmid":1,"date_published":"2022-01-26T00:00:00Z","ddc":["576"],"publication_status":"published","oa":1,"has_accepted_license":"1","intvolume":"        11","citation":{"ama":"Lagator M, Sarikas S, Steinrueck 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>","apa":"Lagator, M., Sarikas, S., Steinrueck, 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, Steinrueck M, Toledo-Aparicio D, Bollback JP, Guet CC, Tkačik G. 2022. Predicting bacterial promoter function and evolution from random sequences. eLife. 11, e64543.","chicago":"Lagator, Mato, Srdjan Sarikas, Magdalena Steinrueck, 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>.","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.","short":"M. Lagator, S. Sarikas, M. Steinrueck, D. Toledo-Aparicio, J.P. Bollback, C.C. Guet, G. Tkačik, ELife 11 (2022)."},"status":"public","external_id":{"isi":["000751104400001"],"pmid":["35080492"]},"volume":11,"file_date_updated":"2022-02-07T07:14:09Z","date_created":"2022-02-06T23:01:32Z","month":"01","type":"journal_article","oa_version":"Published Version","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_updated":"2023-08-02T14:09:02Z","_id":"10736","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.","year":"2022"},{"publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/eLife.78995","quality_controlled":"1","project":[{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Cellular navigation along spatial gradients","grant_number":"724373"},{"_id":"26018E70-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Mechanical adaptation of lamellipodial actin","grant_number":"P29911"}],"isi":1,"language":[{"iso":"eng"}],"author":[{"last_name":"Tomasek","first_name":"Kathrin","full_name":"Tomasek, Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F","last_name":"Leithner"},{"id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d","full_name":"Glatzová, Ivana","first_name":"Ivana","last_name":"Glatzová"},{"full_name":"Lukesch, Michael S.","last_name":"Lukesch","first_name":"Michael S."},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"},{"first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"}],"day":"26","file":[{"date_created":"2022-08-16T08:57:37Z","access_level":"open_access","date_updated":"2022-08-16T08:57:37Z","file_id":"11861","checksum":"002a3c7c7ea5caa9af9cfbea308f6ea4","relation":"main_file","content_type":"application/pdf","file_size":2057577,"creator":"cchlebak","success":1,"file_name":"2022_eLife_Tomasek.pdf"}],"title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","article_number":"e78995","publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"MiSi"},{"_id":"CaGu"}],"publication":"eLife","article_processing_charge":"Yes","scopus_import":"1","ec_funded":1,"article_type":"original","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_status":"published","oa":1,"has_accepted_license":"1","date_published":"2022-07-26T00:00:00Z","ddc":["570"],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"external_id":{"isi":["000838410200001"]},"status":"public","related_material":{"record":[{"relation":"earlier_version","status":"public","id":"10316"}]},"intvolume":"        11","citation":{"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>.","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).","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>","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>."},"date_updated":"2023-08-03T12:54:21Z","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."}],"oa_version":"Published Version","type":"journal_article","month":"07","volume":11,"date_created":"2022-08-14T22:01:46Z","file_date_updated":"2022-08-16T08:57:37Z","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.","year":"2022","_id":"11843"},{"publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"CaGu"}],"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)"},"article_type":"original","scopus_import":"1","article_processing_charge":"No","author":[{"full_name":"Tomanek, Isabella","orcid":"0000-0001-6197-363X","id":"3981F020-F248-11E8-B48F-1D18A9856A87","last_name":"Tomanek","first_name":"Isabella"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet"}],"day":"22","file":[{"date_updated":"2023-01-23T08:56:21Z","file_id":"12338","checksum":"9321fd5f06ff59d5e2d33daee84b3da1","date_created":"2023-01-23T08:56:21Z","access_level":"open_access","success":1,"file_name":"2022_eLife_Tomanek.pdf","relation":"main_file","content_type":"application/pdf","file_size":8835954,"creator":"dernst"}],"article_number":"e82240","title":"Adaptation dynamics between copynumber and point mutations","isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/ELIFE.82240","quality_controlled":"1","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.","year":"2022","_id":"12333","oa_version":"Published Version","type":"journal_article","month":"12","date_updated":"2023-08-03T14:23:07Z","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"}],"volume":11,"file_date_updated":"2023-01-23T08:56:21Z","date_created":"2023-01-22T23:00:55Z","status":"public","external_id":{"isi":["000912674700001"]},"intvolume":"        11","related_material":{"link":[{"url":"https://doi.org/10.5281/zenodo.6974122","relation":"software"}],"record":[{"relation":"research_data","status":"public","id":"12339"}]},"citation":{"ista":"Tomanek I, Guet CC. 2022. Adaptation dynamics between copynumber and point mutations. eLife. 11, e82240.","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>.","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>","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>","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.","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>."},"publication_status":"published","oa":1,"has_accepted_license":"1","date_published":"2022-12-22T00:00:00Z","ddc":["570"]},{"date_updated":"2023-08-03T14:23:06Z","day":"23","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."}],"oa_version":"Published Version","month":"12","type":"research_data_reference","author":[{"full_name":"Tomanek, Isabella","orcid":"0000-0001-6197-363X","id":"3981F020-F248-11E8-B48F-1D18A9856A87","last_name":"Tomanek","first_name":"Isabella"},{"first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"}],"date_created":"2023-01-23T09:00:37Z","title":"Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose","year":"2022","department":[{"_id":"CaGu"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Dryad","article_processing_charge":"No","_id":"12339","oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.5061/dryad.rfj6q57ds"}],"ddc":["570"],"date_published":"2022-12-23T00:00:00Z","doi":"10.5061/dryad.rfj6q57ds","status":"public","citation":{"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>.","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>","short":"I. Tomanek, C.C. Guet, (2022).","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>.","ieee":"I. Tomanek and C. C. Guet, “Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose.” Dryad, 2022."},"related_material":{"record":[{"status":"public","id":"12333","relation":"used_in_publication"}]}},{"_id":"9283","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).","year":"2021","volume":10,"file_date_updated":"2021-03-23T10:12:58Z","date_created":"2021-03-23T10:11:46Z","type":"journal_article","month":"03","oa_version":"Published Version","abstract":[{"lang":"eng","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."}],"date_updated":"2024-02-21T12:41:57Z","intvolume":"        10","related_material":{"record":[{"relation":"research_data","status":"public","id":"8951"}]},"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>","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>","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.","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>.","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>.","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.","short":"A.A. Nagy-Staron, K. Tomasek, C. Caruso Carter, E. Sonnleitner, B. Kavcic, T. Paixão, C.C. Guet, ELife 10 (2021)."},"external_id":{"isi":["000631050900001"]},"status":"public","date_published":"2021-03-08T00:00:00Z","ddc":["570"],"oa":1,"publication_status":"published","has_accepted_license":"1","publication":"eLife","article_type":"original","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)"},"ec_funded":1,"article_processing_charge":"Yes","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"eLife Sciences Publications","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"article_number":"e65993","title":"Local genetic context shapes the function of a gene regulatory network","author":[{"full_name":"Nagy-Staron, Anna A","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1391-8377","last_name":"Nagy-Staron","first_name":"Anna A"},{"last_name":"Tomasek","first_name":"Kathrin","full_name":"Tomasek, Kathrin","orcid":"0000-0003-3768-877X","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Caruso Carter, Caroline","last_name":"Caruso Carter","first_name":"Caroline"},{"full_name":"Sonnleitner, Elisabeth","last_name":"Sonnleitner","first_name":"Elisabeth"},{"first_name":"Bor","last_name":"Kavcic","full_name":"Kavcic, Bor","orcid":"0000-0001-6041-254X","id":"350F91D2-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Paixão, Tiago","last_name":"Paixão","first_name":"Tiago"},{"full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C"}],"day":"08","file":[{"checksum":"3c2f44058c2dd45a5a1027f09d263f8e","file_id":"9284","date_updated":"2021-03-23T10:12:58Z","access_level":"open_access","date_created":"2021-03-23T10:12:58Z","file_name":"elife-65993-v2.pdf","success":1,"creator":"bkavcic","file_size":1390469,"content_type":"application/pdf","relation":"main_file"}],"keyword":["Genetics and Molecular Biology"],"isi":1,"language":[{"iso":"eng"}],"project":[{"grant_number":"628377","call_identifier":"FP7","_id":"2517526A-B435-11E9-9278-68D0E5697425","name":"The Systems Biology of Transcriptional Read-Through in Bacteria: from Synthetic Networks to Genomic Studies"},{"call_identifier":"FWF","_id":"268BFA92-B435-11E9-9278-68D0E5697425","name":"CyberCircuits: Cybergenetic circuits to test composability of gene networks","grant_number":"I03901"}],"doi":"10.7554/elife.65993","quality_controlled":"1","publication_identifier":{"issn":["2050-084X"]}},{"_id":"9647","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).","year":"2021","volume":893,"file_date_updated":"2022-05-12T12:13:27Z","date_created":"2021-07-11T22:01:18Z","page":"1-16","date_updated":"2023-08-10T14:11:19Z","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"}],"month":"06","oa_version":"Published Version","type":"journal_article","intvolume":"       893","citation":{"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>","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>.","ista":"Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. 2021. Long lived transients in gene regulation. Theoretical Computer Science. 893, 1–16.","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>.","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."},"external_id":{"isi":["000710180500002"]},"status":"public","date_published":"2021-06-04T00:00:00Z","ddc":["004"],"publication_status":"published","oa":1,"has_accepted_license":"1","publication":"Theoretical Computer Science","scopus_import":"1","article_processing_charge":"No","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"article_type":"original","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Elsevier","department":[{"_id":"ToHe"},{"_id":"CaGu"}],"title":"Long lived transients in gene regulation","author":[{"full_name":"Petrov, Tatjana","first_name":"Tatjana","last_name":"Petrov"},{"last_name":"Igler","first_name":"Claudia","full_name":"Igler, Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Ali","last_name":"Sezgin","id":"4C7638DA-F248-11E8-B48F-1D18A9856A87","full_name":"Sezgin, Ali"},{"last_name":"Henzinger","first_name":"Thomas A","full_name":"Henzinger, Thomas A","orcid":"0000-0002-2985-7724","id":"40876CD8-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"}],"file":[{"success":1,"file_name":"2021_TheoreticalComputerScience_Petrov.pdf","relation":"main_file","content_type":"application/pdf","file_size":2566504,"creator":"dernst","date_updated":"2022-05-12T12:13:27Z","file_id":"11364","checksum":"d3aef34cfb13e53bba4cf44d01680793","date_created":"2022-05-12T12:13:27Z","access_level":"open_access"}],"day":"04","isi":1,"language":[{"iso":"eng"}],"project":[{"grant_number":"Z211","call_identifier":"FWF","_id":"25F42A32-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize"}],"doi":"10.1016/j.tcs.2021.05.023","quality_controlled":"1","publication_identifier":{"issn":["0304-3975"]}},{"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.","publisher":"Cold Spring Harbor Laboratory","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","year":"2021","department":[{"_id":"CaGu"},{"_id":"MiSi"}],"_id":"10316","publication":"bioRxiv","ec_funded":1,"article_processing_charge":"No","author":[{"first_name":"Kathrin","last_name":"Tomasek","full_name":"Tomasek, Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3768-877X"},{"last_name":"Leithner","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1073-744X","full_name":"Leithner, Alexander F"},{"id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d","full_name":"Glatzová, Ivana","last_name":"Glatzová","first_name":"Ivana"},{"first_name":"Michael S.","last_name":"Lukesch","full_name":"Lukesch, Michael S."},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C"},{"last_name":"Sixt","first_name":"Michael K","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4561-241X"}],"type":"preprint","month":"10","oa_version":"Preprint","abstract":[{"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.","lang":"eng"}],"date_updated":"2024-03-25T23:30:19Z","day":"18","title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","date_created":"2021-11-19T12:24:16Z","project":[{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Cellular navigation along spatial gradients","grant_number":"724373"},{"name":"Mechanical adaptation of lamellipodial actin","_id":"26018E70-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P29911"}],"status":"public","related_material":{"record":[{"status":"public","id":"11843","relation":"later_version"},{"relation":"dissertation_contains","id":"10307","status":"public"}]},"citation":{"short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, BioRxiv (n.d.).","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>.","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.","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>","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>.","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>.","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>"},"language":[{"iso":"eng"}],"publication_status":"submitted","oa":1,"date_published":"2021-10-18T00:00:00Z","doi":"10.1101/2021.10.18.464770","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/2021.10.18.464770v1","open_access":"1"}]},{"volume":13,"date_created":"2021-08-08T22:01:28Z","file_date_updated":"2021-08-09T09:44:03Z","page":"35545–35560","oa_version":"Published Version","type":"journal_article","month":"08","date_updated":"2023-08-10T14:22:48Z","abstract":[{"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.","lang":"eng"}],"_id":"9822","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.","year":"2021","date_published":"2021-08-04T00:00:00Z","ddc":["620","570"],"oa":1,"publication_status":"published","has_accepted_license":"1","intvolume":"        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.","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.","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>.","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.","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>.","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>","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>"},"status":"public","external_id":{"pmid":["34283577"],"isi":["000683741400026"]},"title":"Sequential and switchable patterning for studying cellular processes under spatiotemporal control","author":[{"first_name":"Themistoklis","last_name":"Zisis","full_name":"Zisis, Themistoklis"},{"id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Jan","last_name":"Schwarz","first_name":"Jan"},{"first_name":"Miriam","last_name":"Balles","full_name":"Balles, Miriam"},{"full_name":"Kretschmer, Maibritt","last_name":"Kretschmer","first_name":"Maibritt"},{"id":"34E27F1C-F248-11E8-B48F-1D18A9856A87","full_name":"Nemethova, Maria","last_name":"Nemethova","first_name":"Maria"},{"full_name":"Chait, Remy P","orcid":"0000-0003-0876-3187","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","last_name":"Chait","first_name":"Remy P"},{"first_name":"Robert","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert"},{"first_name":"Janina","last_name":"Lange","full_name":"Lange, Janina"},{"last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-4561-241X","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K"},{"full_name":"Zahler, Stefan","last_name":"Zahler","first_name":"Stefan"}],"day":"04","file":[{"file_name":"2021_ACSAppliedMaterialsAndInterfaces_Zisis.pdf","success":1,"file_size":7123293,"content_type":"application/pdf","relation":"main_file","creator":"asandaue","file_id":"9833","date_updated":"2021-08-09T09:44:03Z","checksum":"b043a91d9f9200e467b970b692687ed3","date_created":"2021-08-09T09:44:03Z","access_level":"open_access"}],"publication":"ACS Applied Materials and Interfaces","article_type":"original","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"ec_funded":1,"article_processing_charge":"Yes (in subscription journal)","scopus_import":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"American Chemical Society","department":[{"_id":"MiSi"},{"_id":"GaTk"},{"_id":"Bio"},{"_id":"CaGu"}],"pmid":1,"doi":"10.1021/acsami.1c09850","quality_controlled":"1","publication_identifier":{"eissn":["19448252"],"issn":["19448244"]},"isi":1,"issue":"30","language":[{"iso":"eng"}],"project":[{"grant_number":"724373","call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","name":"Cellular navigation along spatial gradients"}]},{"date_published":"2020-04-01T00:00:00Z","ddc":["570"],"has_accepted_license":"1","oa":1,"publication_status":"published","citation":{"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>","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>.","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>","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.","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>.","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."},"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"8155"},{"id":"7383","status":"public","relation":"research_data"},{"status":"public","id":"7016","relation":"research_data"},{"status":"public","id":"8653","relation":"used_in_publication"}],"link":[{"url":"https://ist.ac.at/en/news/how-to-thrive-without-gene-regulation/","description":"News on IST Homepage","relation":"press_release"}]},"intvolume":"         4","status":"public","external_id":{"isi":["000519008300005"]},"date_created":"2020-04-08T15:20:53Z","file_date_updated":"2020-10-09T09:56:01Z","volume":4,"oa_version":"Submitted Version","month":"04","type":"journal_article","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_updated":"2024-03-25T23:30:20Z","page":"612-625","_id":"7652","year":"2020","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.","quality_controlled":"1","doi":"10.1038/s41559-020-1132-7","publication_identifier":{"issn":["2397-334X"]},"issue":"4","language":[{"iso":"eng"}],"isi":1,"project":[{"name":"Biophysically realistic genotype-phenotype maps for regulatory networks","_id":"267C84F4-B435-11E9-9278-68D0E5697425"}],"title":"Gene amplification as a form of population-level gene expression regulation","day":"01","file":[{"date_created":"2020-10-09T09:56:01Z","access_level":"open_access","date_updated":"2020-10-09T09:56:01Z","file_id":"8640","checksum":"ef3bbf42023e30b2c24a6278025d2040","relation":"main_file","content_type":"application/pdf","file_size":745242,"creator":"dernst","success":1,"file_name":"2020_NatureEcolEvo_Tomanek.pdf"}],"author":[{"orcid":"0000-0001-6197-363X","id":"3981F020-F248-11E8-B48F-1D18A9856A87","full_name":"Tomanek, Isabella","last_name":"Tomanek","first_name":"Isabella"},{"full_name":"Grah, Rok","orcid":"0000-0003-2539-3560","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","last_name":"Grah","first_name":"Rok"},{"full_name":"Lagator, M.","last_name":"Lagator","first_name":"M."},{"first_name":"A. M. C.","last_name":"Andersson","full_name":"Andersson, A. M. C."},{"first_name":"Jonathan P","last_name":"Bollback","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P"},{"first_name":"Gašper","last_name":"Tkačik","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C"}],"article_type":"original","article_processing_charge":"No","scopus_import":"1","publication":"Nature Ecology & Evolution","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"publisher":"Springer Nature","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8"},{"_id":"6784","year":"2019","volume":15,"file_date_updated":"2020-07-14T12:47:40Z","date_created":"2019-08-11T21:59:19Z","date_updated":"2023-08-29T07:10:06Z","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"}],"type":"journal_article","month":"07","oa_version":"Published Version","intvolume":"        15","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>.","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.","short":"J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, PLoS Computational Biology 15 (2019).","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>","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>","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.","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>."},"status":"public","external_id":{"isi":["000481577700032"]},"ddc":["570"],"date_published":"2019-07-02T00:00:00Z","oa":1,"publication_status":"published","has_accepted_license":"1","publication":"PLoS Computational Biology","scopus_import":"1","article_processing_charge":"No","article_type":"original","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)"},"publisher":"Public Library of Science","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"title":"Molecular noise of innate immunity shapes bacteria-phage ecologies","article_number":"e1007168","author":[{"first_name":"Jakob","last_name":"Ruess","full_name":"Ruess, Jakob","orcid":"0000-0003-1615-3282","id":"4A245D00-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Pleska","first_name":"Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479","full_name":"Pleska, Maros"},{"first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"},{"first_name":"Gašper","last_name":"Tkačik","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"file":[{"file_name":"2019_PlosComputBiology_Ruess.pdf","creator":"dernst","file_size":2200003,"content_type":"application/pdf","relation":"main_file","checksum":"7ded4721b41c2a0fc66a1c634540416a","file_id":"6803","date_updated":"2020-07-14T12:47:40Z","access_level":"open_access","date_created":"2019-08-12T12:27:26Z"}],"day":"02","isi":1,"language":[{"iso":"eng"}],"issue":"7","project":[{"name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level","_id":"251D65D8-B435-11E9-9278-68D0E5697425","grant_number":"24210"},{"grant_number":"RGY0079/2011","name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems","_id":"251BCBEC-B435-11E9-9278-68D0E5697425"}],"doi":"10.1371/journal.pcbi.1007168","quality_controlled":"1","publication_identifier":{"eissn":["1553-7358"]}},{"date_published":"2019-09-17T00:00:00Z","publication_status":"published","intvolume":"     11773","citation":{"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.","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>.","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>","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>","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.","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.","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>."},"alternative_title":["LNCS"],"status":"public","external_id":{"isi":["000557875100009"]},"volume":11773,"date_created":"2019-12-04T16:07:50Z","page":"155-187","date_updated":"2023-09-06T11:18:08Z","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"}],"oa_version":"None","month":"09","type":"conference","_id":"7147","year":"2019","doi":"10.1007/978-3-030-31304-3_9","quality_controlled":"1","publication_identifier":{"eissn":["1611-3349"],"isbn":["9783030313036","9783030313043"],"issn":["0302-9743"]},"isi":1,"conference":{"name":"CMSB: Computational Methods in Systems Biology","location":"Trieste, Italy","start_date":"2019-09-18","end_date":"2019-09-20"},"language":[{"iso":"eng"}],"project":[{"grant_number":"Z211","name":"The Wittgenstein Prize","_id":"25F42A32-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"Design principles underlying genetic switch architecture","_id":"251EE76E-B435-11E9-9278-68D0E5697425","grant_number":"24573"}],"title":"Transient memory in gene regulation","author":[{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C"},{"orcid":"0000−0002−2985−7724","id":"40876CD8-F248-11E8-B48F-1D18A9856A87","full_name":"Henzinger, Thomas A","last_name":"Henzinger","first_name":"Thomas A"},{"last_name":"Igler","first_name":"Claudia","full_name":"Igler, Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87"},{"id":"3D5811FC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9041-0905","full_name":"Petrov, Tatjana","last_name":"Petrov","first_name":"Tatjana"},{"full_name":"Sezgin, Ali","id":"4C7638DA-F248-11E8-B48F-1D18A9856A87","last_name":"Sezgin","first_name":"Ali"}],"day":"17","publication":"17th International Conference on Computational Methods in Systems Biology","article_processing_charge":"No","scopus_import":"1","publisher":"Springer Nature","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","department":[{"_id":"CaGu"},{"_id":"ToHe"}]},{"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","publisher":"Public Library of Science","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"year":"2019","_id":"9786","article_processing_charge":"No","author":[{"orcid":"0000-0003-1615-3282","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","full_name":"Ruess, Jakob","first_name":"Jakob","last_name":"Ruess"},{"orcid":"0000-0001-7460-7479","id":"4569785E-F248-11E8-B48F-1D18A9856A87","full_name":"Pleska, Maros","last_name":"Pleska","first_name":"Maros"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet"},{"full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gašper","last_name":"Tkačik"}],"month":"07","oa_version":"Published Version","type":"research_data_reference","date_updated":"2023-08-29T07:10:05Z","day":"02","title":"Supporting text and results","date_created":"2021-08-06T08:23:43Z","status":"public","related_material":{"record":[{"relation":"used_in_publication","id":"6784","status":"public"}]},"citation":{"short":"J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, (2019).","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>.","ieee":"J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Supporting text and results.” Public Library of Science, 2019.","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>","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>.","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>.","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>"},"date_published":"2019-07-02T00:00:00Z","doi":"10.1371/journal.pcbi.1007168.s001"},{"oa":1,"publication_status":"published","has_accepted_license":"1","date_published":"2018-08-16T00:00:00Z","ddc":["570"],"external_id":{"isi":["000443383300024"]},"status":"public","related_material":{"record":[{"status":"public","id":"9810","relation":"research_data"}]},"intvolume":"        16","citation":{"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>.","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>","short":"W. Chaudhry, M. Pleska, N. Shah, H. Weiss, I. Mccall, J. Meyer, A. Gupta, C.C. Guet, B. Levin, PLoS Biology 16 (2018).","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>.","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."},"oa_version":"Published Version","type":"journal_article","month":"08","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.”."}],"date_updated":"2023-09-13T08:45:41Z","volume":16,"date_created":"2018-12-11T11:44:32Z","file_date_updated":"2020-07-14T12:48:10Z","year":"2018","_id":"82","doi":"10.1371/journal.pbio.2005971","quality_controlled":"1","isi":1,"issue":"8","language":[{"iso":"eng"}],"author":[{"full_name":"Chaudhry, Waqas","last_name":"Chaudhry","first_name":"Waqas"},{"last_name":"Pleska","first_name":"Maros","orcid":"0000-0001-7460-7479","id":"4569785E-F248-11E8-B48F-1D18A9856A87","full_name":"Pleska, Maros"},{"full_name":"Shah, Nilang","first_name":"Nilang","last_name":"Shah"},{"full_name":"Weiss, Howard","last_name":"Weiss","first_name":"Howard"},{"first_name":"Ingrid","last_name":"Mccall","full_name":"Mccall, Ingrid"},{"full_name":"Meyer, Justin","first_name":"Justin","last_name":"Meyer"},{"full_name":"Gupta, Animesh","first_name":"Animesh","last_name":"Gupta"},{"first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"},{"first_name":"Bruce","last_name":"Levin","full_name":"Levin, Bruce"}],"day":"16","file":[{"file_size":4007095,"relation":"main_file","content_type":"application/pdf","creator":"dernst","file_name":"2018_Plos_Chaudhry.pdf","date_created":"2018-12-17T12:55:31Z","access_level":"open_access","file_id":"5706","date_updated":"2020-07-14T12:48:10Z","checksum":"527076f78265cd4ea192cd1569851587"}],"article_number":"2005971","title":"Leaky resistance and the conditions for the existence of lytic bacteriophage","publist_id":"7972","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publisher":"Public Library of Science","department":[{"_id":"CaGu"}],"publication":"PLoS Biology","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_processing_charge":"Yes","scopus_import":"1"},{"oa_version":"Submitted Version","type":"journal_article","month":"09","date_updated":"2024-03-25T23:30:27Z","abstract":[{"lang":"eng","text":"Gene regulatory networks evolve through rewiring of individual components—that is, through changes in regulatory connections. However, the mechanistic basis of regulatory rewiring is poorly understood. Using a canonical gene regulatory system, we quantify the properties of transcription factors that determine the evolutionary potential for rewiring of regulatory connections: robustness, tunability and evolvability. In vivo repression measurements of two repressors at mutated operator sites reveal their contrasting evolutionary potential: while robustness and evolvability were positively correlated, both were in trade-off with tunability. Epistatic interactions between adjacent operators alleviated this trade-off. A thermodynamic model explains how the differences in robustness, tunability and evolvability arise from biophysical characteristics of repressor–DNA binding. The model also uncovers that the energy matrix, which describes how mutations affect repressor–DNA binding, encodes crucial information about the evolutionary potential of a repressor. The biophysical determinants of evolutionary potential for regulatory rewiring constitute a mechanistic framework for understanding network evolution."}],"page":"1633 - 1643","date_created":"2018-12-11T11:44:27Z","file_date_updated":"2020-07-14T12:47:37Z","volume":2,"year":"2018","_id":"67","has_accepted_license":"1","publication_status":"published","oa":1,"date_published":"2018-09-10T00:00:00Z","ddc":["570"],"status":"public","external_id":{"isi":["000447947600021"]},"citation":{"short":"C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, Nature Ecology and Evolution 2 (2018) 1633–1643.","ieee":"C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Evolutionary potential of transcription factors for gene regulatory rewiring,” <i>Nature Ecology and Evolution</i>, vol. 2, no. 10. Nature Publishing Group, pp. 1633–1643, 2018.","chicago":"Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin C Guet. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” <i>Nature Ecology and Evolution</i>. Nature Publishing Group, 2018. <a href=\"https://doi.org/10.1038/s41559-018-0651-y\">https://doi.org/10.1038/s41559-018-0651-y</a>.","ista":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. 2(10), 1633–1643.","mla":"Igler, Claudia, et al. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” <i>Nature Ecology and Evolution</i>, vol. 2, no. 10, Nature Publishing Group, 2018, pp. 1633–43, doi:<a href=\"https://doi.org/10.1038/s41559-018-0651-y\">10.1038/s41559-018-0651-y</a>.","apa":"Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., &#38; Guet, C. C. (2018). Evolutionary potential of transcription factors for gene regulatory rewiring. <i>Nature Ecology and Evolution</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/s41559-018-0651-y\">https://doi.org/10.1038/s41559-018-0651-y</a>","ama":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Evolutionary potential of transcription factors for gene regulatory rewiring. <i>Nature Ecology and Evolution</i>. 2018;2(10):1633-1643. doi:<a href=\"https://doi.org/10.1038/s41559-018-0651-y\">10.1038/s41559-018-0651-y</a>"},"related_material":{"record":[{"relation":"popular_science","id":"5585","status":"public"},{"id":"6371","status":"public","relation":"dissertation_contains"}]},"intvolume":"         2","file":[{"file_size":1135973,"relation":"main_file","content_type":"application/pdf","creator":"dernst","file_name":"2018_NatureEcology_Igler.pdf","date_created":"2020-05-14T11:28:52Z","access_level":"open_access","file_id":"7830","date_updated":"2020-07-14T12:47:37Z","checksum":"383a2e2c944a856e2e821ec8e7bf71b6"}],"day":"10","author":[{"first_name":"Claudia","last_name":"Igler","id":"46613666-F248-11E8-B48F-1D18A9856A87","full_name":"Igler, Claudia"},{"id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato","last_name":"Lagator","first_name":"Mato"},{"first_name":"Gasper","last_name":"Tkacik","full_name":"Tkacik, Gasper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","last_name":"Bollback","first_name":"Jonathan P"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C"}],"publist_id":"7987","title":"Evolutionary potential of transcription factors for gene regulatory rewiring","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"JoBo"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publisher":"Nature Publishing Group","article_type":"original","scopus_import":"1","ec_funded":1,"article_processing_charge":"No","publication":"Nature Ecology and Evolution","quality_controlled":"1","doi":"10.1038/s41559-018-0651-y","project":[{"call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","grant_number":"291734"},{"name":"Selective Barriers to Horizontal Gene Transfer","_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"648440"},{"_id":"251EE76E-B435-11E9-9278-68D0E5697425","name":"Design principles underlying genetic switch architecture (DOC Fellowship)","grant_number":"24573"}],"issue":"10","language":[{"iso":"eng"}],"isi":1},{"year":"2018","_id":"457","page":"359 - 366","type":"journal_article","oa_version":"None","month":"02","abstract":[{"text":"Temperate bacteriophages integrate in bacterial genomes as prophages and represent an important source of genetic variation for bacterial evolution, frequently transmitting fitness-augmenting genes such as toxins responsible for virulence of major pathogens. However, only a fraction of bacteriophage infections are lysogenic and lead to prophage acquisition, whereas the majority are lytic and kill the infected bacteria. Unless able to discriminate lytic from lysogenic infections, mechanisms of immunity to bacteriophages are expected to act as a double-edged sword and increase the odds of survival at the cost of depriving bacteria of potentially beneficial prophages. We show that although restriction-modification systems as mechanisms of innate immunity prevent both lytic and lysogenic infections indiscriminately in individual bacteria, they increase the number of prophage-acquiring individuals at the population level. We find that this counterintuitive result is a consequence of phage-host population dynamics, in which restriction-modification systems delay infection onset until bacteria reach densities at which the probability of lysogeny increases. These results underscore the importance of population-level dynamics as a key factor modulating costs and benefits of immunity to temperate bacteriophages","lang":"eng"}],"date_updated":"2023-09-15T12:04:57Z","volume":2,"date_created":"2018-12-11T11:46:35Z","status":"public","external_id":{"isi":["000426516400027"]},"related_material":{"record":[{"status":"public","id":"202","relation":"dissertation_contains"}]},"intvolume":"         2","citation":{"ieee":"M. Pleska, M. Lang, D. Refardt, B. Levin, and C. C. Guet, “Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity,” <i>Nature Ecology and Evolution</i>, vol. 2, no. 2. Springer Nature, pp. 359–366, 2018.","chicago":"Pleska, Maros, Moritz Lang, Dominik Refardt, Bruce Levin, and Calin C Guet. “Phage-Host Population Dynamics Promotes Prophage Acquisition in Bacteria with Innate Immunity.” <i>Nature Ecology and Evolution</i>. Springer Nature, 2018. <a href=\"https://doi.org/10.1038/s41559-017-0424-z\">https://doi.org/10.1038/s41559-017-0424-z</a>.","short":"M. Pleska, M. Lang, D. Refardt, B. Levin, C.C. Guet, Nature Ecology and Evolution 2 (2018) 359–366.","ama":"Pleska M, Lang M, Refardt D, Levin B, Guet CC. Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. <i>Nature Ecology and Evolution</i>. 2018;2(2):359-366. doi:<a href=\"https://doi.org/10.1038/s41559-017-0424-z\">10.1038/s41559-017-0424-z</a>","mla":"Pleska, Maros, et al. “Phage-Host Population Dynamics Promotes Prophage Acquisition in Bacteria with Innate Immunity.” <i>Nature Ecology and Evolution</i>, vol. 2, no. 2, Springer Nature, 2018, pp. 359–66, doi:<a href=\"https://doi.org/10.1038/s41559-017-0424-z\">10.1038/s41559-017-0424-z</a>.","ista":"Pleska M, Lang M, Refardt D, Levin B, Guet CC. 2018. Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. Nature Ecology and Evolution. 2(2), 359–366.","apa":"Pleska, M., Lang, M., Refardt, D., Levin, B., &#38; Guet, C. C. (2018). Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. <i>Nature Ecology and Evolution</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41559-017-0424-z\">https://doi.org/10.1038/s41559-017-0424-z</a>"},"publication_status":"published","date_published":"2018-02-01T00:00:00Z","publisher":"Springer Nature","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publication":"Nature Ecology and Evolution","scopus_import":"1","article_processing_charge":"No","ec_funded":1,"author":[{"full_name":"Pleska, Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479","last_name":"Pleska","first_name":"Maros"},{"full_name":"Lang, Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","first_name":"Moritz","last_name":"Lang"},{"last_name":"Refardt","first_name":"Dominik","full_name":"Refardt, Dominik"},{"last_name":"Levin","first_name":"Bruce","full_name":"Levin, Bruce"},{"first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"}],"day":"01","title":"Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity","publist_id":"7364","project":[{"grant_number":"291734","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"grant_number":"RGY0079/2011","_id":"251BCBEC-B435-11E9-9278-68D0E5697425","name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems (HFSP Young investigators' grant)"},{"name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)","_id":"251D65D8-B435-11E9-9278-68D0E5697425","grant_number":"24210"}],"isi":1,"issue":"2","language":[{"iso":"eng"}],"doi":"10.1038/s41559-017-0424-z","quality_controlled":"1"},{"date_published":"2018-02-20T00:00:00Z","acknowledged_ssus":[{"_id":"Bio"}],"publication_status":"published","intvolume":"       268","citation":{"ieee":"K. Tomasek, T. Bergmiller, and C. C. Guet, “Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains,” <i>Journal of Biotechnology</i>, vol. 268. Elsevier, pp. 40–52, 2018.","chicago":"Tomasek, Kathrin, Tobias Bergmiller, and Calin C Guet. “Lack of Cations in Flow Cytometry Buffers Affect Fluorescence Signals by Reducing Membrane Stability and Viability of Escherichia Coli Strains.” <i>Journal of Biotechnology</i>. Elsevier, 2018. <a href=\"https://doi.org/10.1016/j.jbiotec.2018.01.008\">https://doi.org/10.1016/j.jbiotec.2018.01.008</a>.","short":"K. Tomasek, T. Bergmiller, C.C. Guet, Journal of Biotechnology 268 (2018) 40–52.","ama":"Tomasek K, Bergmiller T, Guet CC. Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains. <i>Journal of Biotechnology</i>. 2018;268:40-52. doi:<a href=\"https://doi.org/10.1016/j.jbiotec.2018.01.008\">10.1016/j.jbiotec.2018.01.008</a>","mla":"Tomasek, Kathrin, et al. “Lack of Cations in Flow Cytometry Buffers Affect Fluorescence Signals by Reducing Membrane Stability and Viability of Escherichia Coli Strains.” <i>Journal of Biotechnology</i>, vol. 268, Elsevier, 2018, pp. 40–52, doi:<a href=\"https://doi.org/10.1016/j.jbiotec.2018.01.008\">10.1016/j.jbiotec.2018.01.008</a>.","ista":"Tomasek K, Bergmiller T, Guet CC. 2018. Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains. Journal of Biotechnology. 268, 40–52.","apa":"Tomasek, K., Bergmiller, T., &#38; Guet, C. C. (2018). Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains. <i>Journal of Biotechnology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jbiotec.2018.01.008\">https://doi.org/10.1016/j.jbiotec.2018.01.008</a>"},"status":"public","external_id":{"isi":["000425715100006"]},"volume":268,"date_created":"2018-12-11T11:46:50Z","page":"40 - 52","date_updated":"2023-09-13T08:24:51Z","abstract":[{"lang":"eng","text":"Buffers are essential for diluting bacterial cultures for flow cytometry analysis in order to study bacterial physiology and gene expression parameters based on fluorescence signals. Using a variety of constitutively expressed fluorescent proteins in Escherichia coli K-12 strain MG1655, we found strong artifactual changes in fluorescence levels after dilution into the commonly used flow cytometry buffer phosphate-buffered saline (PBS) and two other buffer solutions, Tris-HCl and M9 salts. These changes appeared very rapidly after dilution, and were linked to increased membrane permeability and loss in cell viability. We observed buffer-related effects in several different E. coli strains, K-12, C and W, but not E. coli B, which can be partially explained by differences in lipopolysaccharide (LPS) and outer membrane composition. Supplementing the buffers with divalent cations responsible for outer membrane stability, Mg2+ and Ca2+, preserved fluorescence signals, membrane integrity and viability of E. coli. Thus, stabilizing the bacterial outer membrane is essential for precise and unbiased measurements of fluorescence parameters using flow cytometry."}],"oa_version":"None","month":"02","type":"journal_article","_id":"503","acknowledgement":"We thank R Chait and M Lagator for sharing Bacillus subtilis CR_Y1 and pZS*_2R-cIPtet-Venus-Prm, respectively. We are grateful to T Pilizota and all members of the Guet lab for critically reading the manuscript. We also thank the Bioimaging facility at IST Austria for assistance using the FACSAria III system.\r\n\r\n","year":"2018","doi":"10.1016/j.jbiotec.2018.01.008","quality_controlled":"1","isi":1,"language":[{"iso":"eng"}],"title":"Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains","publist_id":"7317","author":[{"full_name":"Tomasek, Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3768-877X","first_name":"Kathrin","last_name":"Tomasek"},{"full_name":"Bergmiller, Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","first_name":"Tobias","last_name":"Bergmiller"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet"}],"day":"20","publication":"Journal of Biotechnology","article_processing_charge":"No","scopus_import":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publisher":"Elsevier","department":[{"_id":"CaGu"}]},{"related_material":{"record":[{"relation":"research_paper","id":"67","status":"public"},{"id":"6371","status":"public","relation":"research_paper"}]},"citation":{"ieee":"C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring.” Institute of Science and Technology Austria, 2018.","chicago":"Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin C Guet. “Data for the Paper Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” Institute of Science and Technology Austria, 2018. <a href=\"https://doi.org/10.15479/AT:ISTA:108\">https://doi.org/10.15479/AT:ISTA:108</a>.","short":"C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, (2018).","ama":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring. 2018. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:108\">10.15479/AT:ISTA:108</a>","ista":"Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:108\">10.15479/AT:ISTA:108</a>.","mla":"Igler, Claudia, et al. <i>Data for the Paper Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring</i>. Institute of Science and Technology Austria, 2018, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:108\">10.15479/AT:ISTA:108</a>.","apa":"Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., &#38; Guet, C. C. (2018). Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:108\">https://doi.org/10.15479/AT:ISTA:108</a>"},"project":[{"name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"},{"_id":"2578D616-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer","grant_number":"648440"},{"_id":"251EE76E-B435-11E9-9278-68D0E5697425","name":"Design principles underlying genetic switch architecture (DOC Fellowship)","grant_number":"24573"}],"status":"public","doi":"10.15479/AT:ISTA:108","date_published":"2018-07-20T00:00:00Z","ddc":["576"],"oa":1,"has_accepted_license":"1","_id":"5585","tmp":{"name":"Creative Commons Public Domain Dedication (CC0 1.0)","short":"CC0 (1.0)","image":"/images/cc_0.png","legal_code_url":"https://creativecommons.org/publicdomain/zero/1.0/legalcode"},"ec_funded":1,"article_processing_charge":"No","publisher":"Institute of Science and Technology Austria","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","datarep_id":"108","year":"2018","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"title":"Data for the paper Evolutionary potential of transcription factors for gene regulatory rewiring","file_date_updated":"2020-07-14T12:47:07Z","date_created":"2018-12-12T12:31:40Z","author":[{"first_name":"Claudia","last_name":"Igler","id":"46613666-F248-11E8-B48F-1D18A9856A87","full_name":"Igler, Claudia"},{"first_name":"Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato"},{"last_name":"Tkacik","first_name":"Gasper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","full_name":"Tkacik, Gasper"},{"first_name":"Jonathan P","last_name":"Bollback","full_name":"Bollback, Jonathan P","orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"month":"07","type":"research_data","oa_version":"Published Version","day":"20","file":[{"date_created":"2018-12-12T13:02:45Z","access_level":"open_access","file_id":"5611","date_updated":"2020-07-14T12:47:07Z","checksum":"1435781526c77413802adee0d4583cce","file_size":16507,"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","relation":"main_file","creator":"system","file_name":"IST-2018-108-v1+1_data_figures.xlsx"}],"abstract":[{"text":"Mean repression values and standard error of the mean are given for all operator mutant libraries.","lang":"eng"}],"date_updated":"2024-03-25T23:30:27Z"},{"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)"},"ec_funded":1,"scopus_import":"1","article_processing_charge":"No","publication":"Nature Communications","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"publisher":"Springer Nature","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publist_id":"7760","article_number":"2988","title":"Statistical mechanics for metabolic networks during steady state growth","day":"30","file":[{"checksum":"3ba7ab27b27723c7dcf633e8fc1f8f18","file_id":"5728","date_updated":"2020-07-14T12:45:06Z","access_level":"open_access","date_created":"2018-12-17T16:44:28Z","file_name":"2018_NatureComm_DeMartino.pdf","creator":"dernst","file_size":1043205,"content_type":"application/pdf","relation":"main_file"}],"author":[{"full_name":"De Martino, Daniele","orcid":"0000-0002-5214-4706","id":"3FF5848A-F248-11E8-B48F-1D18A9856A87","last_name":"De Martino","first_name":"Daniele"},{"first_name":"Andersson Anna","last_name":"Mc","full_name":"Mc, Andersson Anna"},{"first_name":"Tobias","last_name":"Bergmiller","full_name":"Bergmiller, Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C"},{"first_name":"Gasper","last_name":"Tkacik","full_name":"Tkacik, Gasper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"issue":"1","language":[{"iso":"eng"}],"isi":1,"project":[{"grant_number":"P28844-B27","_id":"254E9036-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Biophysics of information processing in gene regulation"},{"grant_number":"291734","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"quality_controlled":"1","doi":"10.1038/s41467-018-05417-9","_id":"161","year":"2018","date_created":"2018-12-11T11:44:57Z","file_date_updated":"2020-07-14T12:45:06Z","volume":9,"oa_version":"Published Version","month":"07","type":"journal_article","date_updated":"2024-02-21T13:45:39Z","abstract":[{"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.","lang":"eng"}],"citation":{"short":"D. De Martino, A.A. Mc, T. Bergmiller, C.C. Guet, G. Tkačik, Nature Communications 9 (2018).","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.","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>.","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.","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>.","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>","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>"},"related_material":{"record":[{"id":"5587","status":"public","relation":"popular_science"}]},"intvolume":"         9","external_id":{"isi":["000440149300021"]},"status":"public","date_published":"2018-07-30T00:00:00Z","ddc":["570"],"has_accepted_license":"1","oa":1,"publication_status":"published"},{"article_processing_charge":"No","_id":"9810","department":[{"_id":"CaGu"}],"year":"2018","publisher":"Public Library of Science","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","date_created":"2021-08-06T12:43:44Z","title":"Numerical data used in figures","day":"16","date_updated":"2023-09-13T08:45:41Z","month":"08","oa_version":"Published Version","type":"research_data_reference","author":[{"first_name":"Waqas","last_name":"Chaudhry","full_name":"Chaudhry, Waqas"},{"orcid":"0000-0001-7460-7479","id":"4569785E-F248-11E8-B48F-1D18A9856A87","full_name":"Pleska, Maros","last_name":"Pleska","first_name":"Maros"},{"full_name":"Shah, Nilang","last_name":"Shah","first_name":"Nilang"},{"first_name":"Howard","last_name":"Weiss","full_name":"Weiss, Howard"},{"full_name":"Mccall, Ingrid","last_name":"Mccall","first_name":"Ingrid"},{"first_name":"Justin","last_name":"Meyer","full_name":"Meyer, Justin"},{"full_name":"Gupta, Animesh","first_name":"Animesh","last_name":"Gupta"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"},{"first_name":"Bruce","last_name":"Levin","full_name":"Levin, Bruce"}],"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>","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>.","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>.","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>","ieee":"W. Chaudhry <i>et al.</i>, “Numerical data used in figures.” Public Library of Science, 2018.","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)."},"related_material":{"record":[{"status":"public","id":"82","relation":"used_in_publication"}]},"status":"public","date_published":"2018-08-16T00:00:00Z","doi":"10.1371/journal.pbio.2005971.s008"}]