[{"arxiv":1,"date_published":"2026-05-09T00:00:00Z","title":"Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps","publication_identifier":{"eissn":["1879-0380"],"issn":["0959-437X"]},"main_file_link":[{"url":"https://doi.org/10.1016/j.gde.2026.102483","open_access":"1"}],"oa_version":"Published Version","acknowledgement":"We thank Nick Barton and Noa Ottilie Borst for essential contributions to this manuscript.\r\nE.M. acknowledges support from the APART-USA fellowship, jointly funded by the Austrian Academy of Sciences (ÖAW) and the Institute of Science and Technology Austria (ISTA).\r\nThis study was supported by the European Molecular Biology Laboratory (J.C.); the European Molecular Biology Laboratory Interdisciplinary Postdoc Programme (EIPOD) under the Marie Skłodowska-Curie Actions cofund (S.H.A.).","_id":"21983","external_id":{"arxiv":["2601.19681"]},"publication":"Current Opinion in Genetics & Development","scopus_import":"1","author":[{"last_name":"Mascolo","full_name":"Mascolo, Elia","first_name":"Elia","id":"776a6ed0-a053-11f0-8635-80b95e0e0d53","orcid":"0000-0003-2977-7844"},{"first_name":"Reka E","last_name":"Körei","id":"50FDE43E-AA30-11E9-A72B-8A12E6697425","full_name":"Körei, Reka E"},{"first_name":"Santiago","full_name":"Herrera-Álvarez, Santiago","last_name":"Herrera-Álvarez"},{"orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"},{"full_name":"Crocker, Justin","first_name":"Justin","last_name":"Crocker"},{"orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik","full_name":"Tkačik, Gašper","first_name":"Gašper"}],"day":"09","date_updated":"2026-06-16T12:37:02Z","abstract":[{"text":"Promoters and enhancers are cis-regulatory elements (CREs), DNA sequences that bind transcription factor (TF) proteins to up- or down-regulate target genes. Decades-long efforts yielded TF-DNA interaction models that predict how strongly an individual TF binds arbitrary DNA sequences and how individual binding events on the CRE combine to affect gene expression. These insights can be synthesized into a global, biophysically realistic, and quantitative genotype–phenotype map for gene regulation, a ‘holy grail’ for the application of evolutionary theory. A global map provides a rare opportunity to simulate the long-term evolution of regulatory sequences and pose several fundamental questions: How long does it take to evolve CREs de novo? How many non-trivial regulatory functions exist in sequence space? How connected are they? For which regulatory architecture is CRE evolution most rapid and evolvable? In this article, the first of a two-part series, we briefly review the pertinent modeling and simulation efforts for a unique system that enables close, quantitative, and mechanistic links between biophysics, as well as systems, synthetic, and evolutionary biology.","lang":"eng"}],"fulldoi":"https://doi.org/10.1016/j.gde.2026.102483","language":[{"iso":"eng"}],"month":"05","has_accepted_license":"1","status":"public","department":[{"_id":"GradSch"},{"_id":"CaGu"},{"_id":"GaTk"}],"article_processing_charge":"Yes (via OA deal)","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)"},"type":"journal_article","date_created":"2026-06-10T07:37:12Z","volume":99,"intvolume":"        99","OA_type":"hybrid","publisher":"Elsevier","oa":1,"OA_place":"publisher","article_type":"original","article_number":"102483","corr_author":"1","PlanS_conform":"1","publication_status":"published","citation":{"ieee":"E. Mascolo, R. E. Körei, S. Herrera-Álvarez, C. C. Guet, J. Crocker, and G. Tkačik, “Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps,” <i>Current Opinion in Genetics &#38; Development</i>, vol. 99. Elsevier, 2026.","apa":"Mascolo, E., Körei, R. E., Herrera-Álvarez, S., Guet, C. C., Crocker, J., &#38; Tkačik, G. (2026). Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps. <i>Current Opinion in Genetics &#38; Development</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.gde.2026.102483\">https://doi.org/10.1016/j.gde.2026.102483</a>","ista":"Mascolo E, Körei RE, Herrera-Álvarez S, Guet CC, Crocker J, Tkačik G. 2026. Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps. Current Opinion in Genetics &#38; Development. 99, 102483.","mla":"Mascolo, Elia, et al. “Long-Term Evolution of Regulatory DNA Sequences. Part 1: Simulations on Global, Biophysically-Realistic Genotype–Phenotype Maps.” <i>Current Opinion in Genetics &#38; Development</i>, vol. 99, 102483, Elsevier, 2026, doi:<a href=\"https://doi.org/10.1016/j.gde.2026.102483\">10.1016/j.gde.2026.102483</a>.","chicago":"Mascolo, Elia, Reka E Körei, Santiago Herrera-Álvarez, Calin C Guet, Justin Crocker, and Gašper Tkačik. “Long-Term Evolution of Regulatory DNA Sequences. Part 1: Simulations on Global, Biophysically-Realistic Genotype–Phenotype Maps.” <i>Current Opinion in Genetics &#38; Development</i>. Elsevier, 2026. <a href=\"https://doi.org/10.1016/j.gde.2026.102483\">https://doi.org/10.1016/j.gde.2026.102483</a>.","short":"E. Mascolo, R.E. Körei, S. Herrera-Álvarez, C.C. Guet, J. Crocker, G. Tkačik, Current Opinion in Genetics &#38; Development 99 (2026).","ama":"Mascolo E, Körei RE, Herrera-Álvarez S, Guet CC, Crocker J, Tkačik G. Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps. <i>Current Opinion in Genetics &#38; Development</i>. 2026;99. doi:<a href=\"https://doi.org/10.1016/j.gde.2026.102483\">10.1016/j.gde.2026.102483</a>"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"quality_controlled":"1","year":"2026","doi":"10.1016/j.gde.2026.102483"},{"volume":80,"date_created":"2026-06-10T07:38:12Z","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 (via OA deal)","type":"journal_article","language":[{"iso":"eng"}],"month":"06","has_accepted_license":"1","department":[{"_id":"CaGu"}],"status":"public","day":"01","date_updated":"2026-06-16T12:46:02Z","abstract":[{"lang":"eng","text":"Upon infecting a bacterial cell, temperate phages make a decision between lysis and lysogeny. While research has previously explored how phages sense environmental information to make this choice, most studies have focused on modelling known mechanisms that impact the decision. These mechanisms tell us what environmental information the phage does respond to, but not what it should respond to, as the signals sensed by the phage may serve as proxies for other sources of information. Here, using a mechanism-agnostic population dynamics model, we find that irreversible phage binding to lysogens protects sensitive host cells from infection. This results in lysogens being an additional environmental factor that the phage should sense while making its decision to undergo lysis or lysogeny. Using this model, we derive a responsive lysogeny probability for phages that respond to both cell and lysogen densities optimized towards invading phage-occupied systems, and show that it is more capable of invading and resisting invasion than phage with fixed lysogeny probabilities across different environmental conditions."}],"fulldoi":"https://doi.org/10.1093/evolut/qpag061","external_id":{"pmid":["41968110"]},"scopus_import":"1","author":[{"full_name":"Wu, Bryan","last_name":"Wu","id":"3C521EBA-F248-11E8-B48F-1D18A9856A87","first_name":"Bryan"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","full_name":"Guet, Calin C","first_name":"Calin C","orcid":"0000-0001-6220-2052"}],"publication":"Evolution","oa_version":"Published Version","acknowledgement":"We thank Fyodor Kondrashov and Gašper Tkačik for valuable input and guidance in building the model, and Stephen Abedon as well as the two anonymous reviewers for the comments provided on the manuscript.","_id":"21985","title":"Responsive lysogeny under nonproductive phage binding","publication_identifier":{"eissn":["1558-5646"],"issn":["0014-3820"]},"file_date_updated":"2026-06-16T12:45:09Z","date_published":"2026-06-01T00:00:00Z","year":"2026","doi":"10.1093/evolut/qpag061","page":"1365-1373","ddc":["570"],"quality_controlled":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","PlanS_conform":"1","publication_status":"published","citation":{"short":"B. Wu, C.C. Guet, Evolution 80 (2026) 1365–1373.","ama":"Wu B, Guet CC. Responsive lysogeny under nonproductive phage binding. <i>Evolution</i>. 2026;80(6):1365-1373. doi:<a href=\"https://doi.org/10.1093/evolut/qpag061\">10.1093/evolut/qpag061</a>","ista":"Wu B, Guet CC. 2026. Responsive lysogeny under nonproductive phage binding. Evolution. 80(6), 1365–1373.","apa":"Wu, B., &#38; Guet, C. C. (2026). Responsive lysogeny under nonproductive phage binding. <i>Evolution</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/evolut/qpag061\">https://doi.org/10.1093/evolut/qpag061</a>","ieee":"B. Wu and C. C. Guet, “Responsive lysogeny under nonproductive phage binding,” <i>Evolution</i>, vol. 80, no. 6. Oxford University Press, pp. 1365–1373, 2026.","chicago":"Wu, Bryan, and Calin C Guet. “Responsive Lysogeny under Nonproductive Phage Binding.” <i>Evolution</i>. Oxford University Press, 2026. <a href=\"https://doi.org/10.1093/evolut/qpag061\">https://doi.org/10.1093/evolut/qpag061</a>.","mla":"Wu, Bryan, and Calin C. Guet. “Responsive Lysogeny under Nonproductive Phage Binding.” <i>Evolution</i>, vol. 80, no. 6, Oxford University Press, 2026, pp. 1365–73, doi:<a href=\"https://doi.org/10.1093/evolut/qpag061\">10.1093/evolut/qpag061</a>."},"article_type":"original","pmid":1,"related_material":{"link":[{"url":"https://github.com/theguetlab/responsive-lysogeny","relation":"software"}]},"oa":1,"OA_place":"publisher","intvolume":"        80","OA_type":"hybrid","publisher":"Oxford University Press","issue":"6","file":[{"access_level":"open_access","creator":"dernst","success":1,"file_id":"22015","checksum":"6d0f48566a7a36cb0c469e1968c9cb1c","date_updated":"2026-06-16T12:45:09Z","file_name":"2026_Evolution_Wu.pdf","date_created":"2026-06-16T12:45:09Z","file_size":2077781,"relation":"main_file","content_type":"application/pdf"}]},{"file_date_updated":"2026-06-02T07:11:12Z","date_published":"2026-05-20T00:00:00Z","title":"Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope","publication_identifier":{"eissn":["2041-1723"]},"oa_version":"Published Version","acknowledgement":"We are very grateful to S. Hernando-Amado (Madrid, Spain), C. Pál (Szeged, Hungary), and T. Bollenbach (Cologne, Germany) for critical comments and advice on the manuscript. We further thank D. Rogers, J. Summers (Ploen, Germany) for guidance in allelic exchange, P. Rainey (Ploen, Germany) for providing the plasmids and strains, then J. Lorenzen, K. Flinder, N. Steinbach, S. Butze (all Schulenburg lab), and L. Kirchhoff (Rupp lab) for supporting the experimental work, and also the Rupp and Schulenburg groups for general feedback. We are grateful for financial support from the German Research Foundation within the Research and Training Group 2501 (RTG 2501) on Translational Evolutionary Research (project 4.2 to H.S.), within the Excellence cluster Precision Medicine in chronic Inflammation (PMI; funding under Germany’s Excellence Strategy EXC 2167-390884018, to B.K., K.R., J.R., H.S.), within the Clinician Scientist Program in Evolutionary Medicine (CSEM) – project number 413490537 (to EEG), and as part of the individual grants SCHU 1415/12-2 (to H.S.) and BR-2915/7-1 (to M.B.). We are grateful for financial support from the Swedish Research Council, project number 2021-02091 (to D.I.A.). We are also grateful for financial support from the Max-Planck Society (Fellowship to H.S.), the Leibniz Association within the Leibniz Science-Campus Evolutionary Medicine of the Lung (EvoLUNG, to H.S.), and the project SKILLED funded by the DAMP foundation (to J.R., H.S.). This work was also supported by the ZMB Young Scientist award and the FWF grant 10.55776/ESP219 (to R.R.) and the TransEvo Innovation prize (to F.B.). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Open Access funding enabled and organized by Projekt DEAL.\r\n","_id":"21928","author":[{"full_name":"Buchholz, Florian","first_name":"Florian","last_name":"Buchholz"},{"last_name":"Upterworth","first_name":"Lina M.","full_name":"Upterworth, Lina M."},{"first_name":"Leif","full_name":"Tueffers, Leif","last_name":"Tueffers"},{"last_name":"Groth","full_name":"Groth, Espen E.","first_name":"Espen E."},{"full_name":"Haas, Kira","last_name":"Haas","first_name":"Kira"},{"first_name":"Daniel","full_name":"Schütz, Daniel","last_name":"Schütz"},{"first_name":"Abigail","full_name":"Savietto Scholz, Abigail","last_name":"Savietto Scholz"},{"first_name":"Aditi","full_name":"Batra, Aditi","last_name":"Batra"},{"full_name":"Pal, Surajit","first_name":"Surajit","last_name":"Pal"},{"full_name":"Banerjee, Samarpita","last_name":"Banerjee","first_name":"Samarpita"},{"last_name":"Dubey","first_name":"Badri N.","full_name":"Dubey, Badri N."},{"full_name":"Franzenburg, Sören","first_name":"Sören","last_name":"Franzenburg"},{"first_name":"Barbara","full_name":"Kalsdorf, Barbara","last_name":"Kalsdorf"},{"last_name":"Rabe","first_name":"Klaus F.","full_name":"Rabe, Klaus F."},{"first_name":"Dennis","last_name":"Nurjadi","full_name":"Nurjadi, Dennis"},{"last_name":"Rupp","first_name":"Jan","full_name":"Rupp, Jan"},{"full_name":"Andersson, Dan I.","last_name":"Andersson","first_name":"Dan I."},{"full_name":"Sondermann, Holger","last_name":"Sondermann","first_name":"Holger"},{"full_name":"Bramkamp, Marc","first_name":"Marc","last_name":"Bramkamp"},{"full_name":"Römhild, Roderich","first_name":"Roderich","last_name":"Römhild","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","orcid":"0000-0001-9480-5261"},{"full_name":"Schulenburg, Hinrich","first_name":"Hinrich","last_name":"Schulenburg"}],"scopus_import":"1","publication":"Nature Communications","date_updated":"2026-06-02T07:14:35Z","day":"20","abstract":[{"text":"Antibiotic combination in time and space is a key strategy to combat antimicrobial resistance. The success of such treatment designs requires their robust efficacy across treatment conditions and a pathogen’s genomic diversity. This study found that an initial treatment with a β-lactam antibiotic causes robust cellular sensitization towards an aminoglycoside antibiotic across the high-risk human pathogen Pseudomonas aeruginosa, including resistant strains. This phenomenon of cellular sensitization, termed negative hysteresis, is modulated by the Cpx envelope stress response system and linked to membrane stress during growth. The increase in efficacy is achieved through a β-lactam induced elevated cellular uptake of the subsequently administered aminoglycoside. Negative hysteresis and the Cpx system are linked in several cases to the expression of synergistic drug interactions, thus enhancing efficacy of antibiotic combinations. Overall, our study identifies the phenomenon of negative hysteresis as a robustly inducible phenotype and thus a unique focus for optimizing antimicrobial therapy.","lang":"eng"}],"fulldoi":"https://doi.org/10.1038/s41467-026-71178-5","language":[{"iso":"eng"}],"month":"05","has_accepted_license":"1","department":[{"_id":"CaGu"}],"status":"public","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)"},"type":"journal_article","article_processing_charge":"Yes (via OA deal)","DOAJ_listed":"1","date_created":"2026-05-31T22:02:12Z","volume":17,"file":[{"date_updated":"2026-06-02T07:11:12Z","file_name":"2026_NatureComm_Buchholz.pdf","success":1,"creator":"dernst","access_level":"open_access","checksum":"aa29f8806908dc0469dff21e2d5ad01f","file_id":"21936","file_size":1276166,"relation":"main_file","content_type":"application/pdf","date_created":"2026-06-02T07:11:12Z"}],"OA_type":"gold","intvolume":"        17","publisher":"Springer Nature","oa":1,"project":[{"name":"Non-canonical antibiotic interactions","grant_number":"E219","_id":"bd6f94d1-d553-11ed-ba76-ae9f07250f74"}],"OA_place":"publisher","article_type":"original","article_number":"4487","corr_author":"1","PlanS_conform":"1","publication_status":"published","citation":{"short":"F. Buchholz, L.M. Upterworth, L. Tueffers, E.E. Groth, K. Haas, D. Schütz, A. Savietto Scholz, A. Batra, S. Pal, S. Banerjee, B.N. Dubey, S. Franzenburg, B. Kalsdorf, K.F. Rabe, D. Nurjadi, J. Rupp, D.I. Andersson, H. Sondermann, M. Bramkamp, R. Römhild, H. Schulenburg, Nature Communications 17 (2026).","ama":"Buchholz F, Upterworth LM, Tueffers L, et al. Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope. <i>Nature Communications</i>. 2026;17. doi:<a href=\"https://doi.org/10.1038/s41467-026-71178-5\">10.1038/s41467-026-71178-5</a>","chicago":"Buchholz, Florian, Lina M. Upterworth, Leif Tueffers, Espen E. Groth, Kira Haas, Daniel Schütz, Abigail Savietto Scholz, et al. “Robust Antibiotic Sensitization of Pathogenic Pseudomonas Aeruginosa via Negative Hysteresis in the Cell Envelope.” <i>Nature Communications</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41467-026-71178-5\">https://doi.org/10.1038/s41467-026-71178-5</a>.","mla":"Buchholz, Florian, et al. “Robust Antibiotic Sensitization of Pathogenic Pseudomonas Aeruginosa via Negative Hysteresis in the Cell Envelope.” <i>Nature Communications</i>, vol. 17, 4487, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41467-026-71178-5\">10.1038/s41467-026-71178-5</a>.","ista":"Buchholz F, Upterworth LM, Tueffers L, Groth EE, Haas K, Schütz D, Savietto Scholz A, Batra A, Pal S, Banerjee S, Dubey BN, Franzenburg S, Kalsdorf B, Rabe KF, Nurjadi D, Rupp J, Andersson DI, Sondermann H, Bramkamp M, Römhild R, Schulenburg H. 2026. Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope. Nature Communications. 17, 4487.","apa":"Buchholz, F., Upterworth, L. M., Tueffers, L., Groth, E. E., Haas, K., Schütz, D., … Schulenburg, H. (2026). Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-026-71178-5\">https://doi.org/10.1038/s41467-026-71178-5</a>","ieee":"F. Buchholz <i>et al.</i>, “Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope,” <i>Nature Communications</i>, vol. 17. Springer Nature, 2026."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"quality_controlled":"1","year":"2026","doi":"10.1038/s41467-026-71178-5"},{"year":"2026","doi":"10.15479/AT-ISTA-22981","page":"102","degree_awarded":"PhD","ddc":["570","576","579"],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","publication_status":"published","citation":{"short":"N. Gruber, Genetic Strategies Enabling Bacterial Adaptation to Selective Pressures, Institute of Science and Technology Austria, 2026.","ama":"Gruber N. Genetic strategies enabling bacterial adaptation to selective pressures. 2026. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22981\">10.15479/AT-ISTA-22981</a>","ista":"Gruber N. 2026. Genetic strategies enabling bacterial adaptation to selective pressures. Institute of Science and Technology Austria.","apa":"Gruber, N. (2026). <i>Genetic strategies enabling bacterial adaptation to selective pressures</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-22981\">https://doi.org/10.15479/AT-ISTA-22981</a>","ieee":"N. Gruber, “Genetic strategies enabling bacterial adaptation to selective pressures,” Institute of Science and Technology Austria, 2026.","chicago":"Gruber, Nathalie. “Genetic Strategies Enabling Bacterial Adaptation to Selective Pressures.” Institute of Science and Technology Austria, 2026. <a href=\"https://doi.org/10.15479/AT-ISTA-22981\">https://doi.org/10.15479/AT-ISTA-22981</a>.","mla":"Gruber, Nathalie. <i>Genetic Strategies Enabling Bacterial Adaptation to Selective Pressures</i>. Institute of Science and Technology Austria, 2026, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22981\">10.15479/AT-ISTA-22981</a>."},"corr_author":"1","OA_place":"publisher","supervisor":[{"orcid":"0000-0001-6220-2052","first_name":"Calin C","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet"}],"project":[{"name":"Uncovering the organisational principle of bacterial genomic islands in Anti-phage defense","_id":"34cb8730-11ca-11ed-8bc3-8b3b3752a6f6","grant_number":"26422"}],"publisher":"Institute of Science and Technology Austria","alternative_title":["ISTA Thesis"],"file":[{"file_name":"2026_Gruber_Nathalie_Thesis.pdf","date_updated":"2026-10-01T12:34:18Z","checksum":"64a61a8812cefaaeffc247a409d46a23","file_id":"23020","creator":"ngruber","access_level":"closed","embargo":"2027-10-01","content_type":"application/pdf","relation":"main_file","file_size":48619027,"embargo_to":"open_access","date_created":"2026-10-01T09:00:53Z"},{"checksum":"942f6291750664d6d1adfb4f8b5a1735","file_id":"23021","creator":"ngruber","access_level":"closed","file_name":"2026_Gruber_Nathalie_Thesis.docx","date_updated":"2026-10-01T11:49:41Z","date_created":"2026-10-01T09:31:20Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":55175414,"relation":"source_file"}],"date_created":"2026-09-23T12:25:43Z","article_processing_charge":"No","type":"dissertation","status":"public","department":[{"_id":"GradSch"},{"_id":"CaGu"}],"month":"09","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"language":[{"iso":"eng"}],"has_accepted_license":"1","doi_confirm":"1","fulldoi":"https://doi.org/10.15479/AT-ISTA-22981","date_updated":"2026-10-02T10:52:13Z","day":"24","author":[{"full_name":"Gruber, Nathalie","last_name":"Gruber","first_name":"Nathalie","id":"2C9C8316-AA17-11E9-B5C2-8BC2E5697425"}],"acknowledgement":"I want to acknowledge the Austrian Academy of Sciences for funding through the DOC \r\nFellowship program (fellowship number 26422) and for the honest and inspirational talk by \r\nAnton Zeilinger at the award ceremony about the PhD journey. ","_id":"22981","oa_version":"Published Version","title":"Genetic strategies enabling bacterial adaptation to selective pressures","publication_identifier":{"issn":["2663-337X"]},"file_date_updated":"2026-10-01T12:34:18Z","date_published":"2026-09-24T00:00:00Z"},{"publisher":"Oxford University Press","issue":"10","intvolume":"        43","OA_type":"gold","keyword":["homologous recombination","defense systems","CRISPR-Cas","herd immunity","stationary phase","bacterial evolution"],"pmid":1,"supplementarymaterial":"yes","article_number":"msag238","article_type":"original","OA_place":"publisher","oa":1,"das_tickbox":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ama":"Payne P, Plevka P, Bollback JP, Guet CC. Herd immunity underlies homologous recombination in stationary phase bacteria. <i>Molecular Biology and Evolution</i>. 2026;43(10). doi:<a href=\"https://doi.org/10.1093/molbev/msag238\">10.1093/molbev/msag238</a>","short":"P. Payne, P. Plevka, J.P. Bollback, C.C. Guet, Molecular Biology and Evolution 43 (2026).","ista":"Payne P, Plevka P, Bollback JP, Guet CC. 2026. Herd immunity underlies homologous recombination in stationary phase bacteria. Molecular Biology and Evolution. 43(10), msag238.","ieee":"P. Payne, P. Plevka, J. P. Bollback, and C. C. Guet, “Herd immunity underlies homologous recombination in stationary phase bacteria,” <i>Molecular Biology and Evolution</i>, vol. 43, no. 10. Oxford University Press, 2026.","apa":"Payne, P., Plevka, P., Bollback, J. P., &#38; Guet, C. C. (2026). Herd immunity underlies homologous recombination in stationary phase bacteria. <i>Molecular Biology and Evolution</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/molbev/msag238\">https://doi.org/10.1093/molbev/msag238</a>","chicago":"Payne, Pavel, Pavel Plevka, Jonathan P Bollback, and Calin C Guet. “Herd Immunity Underlies Homologous Recombination in Stationary Phase Bacteria.” <i>Molecular Biology and Evolution</i>. Oxford University Press, 2026. <a href=\"https://doi.org/10.1093/molbev/msag238\">https://doi.org/10.1093/molbev/msag238</a>.","mla":"Payne, Pavel, et al. “Herd Immunity Underlies Homologous Recombination in Stationary Phase Bacteria.” <i>Molecular Biology and Evolution</i>, vol. 43, no. 10, msag238, Oxford University Press, 2026, doi:<a href=\"https://doi.org/10.1093/molbev/msag238\">10.1093/molbev/msag238</a>."},"publication_status":"epub_ahead","researchdata_availability":"no","corr_author":"1","doi":"10.1093/molbev/msag238","year":"2026","quality_controlled":"1","ddc":["570"],"publication_identifier":{"eissn":["1537-1719"],"issn":["0737-4038"]},"title":"Herd immunity underlies homologous recombination in stationary phase bacteria","date_published":"2026-10-03T00:00:00Z","author":[{"orcid":"0000-0002-2711-9453","id":"35F78294-F248-11E8-B48F-1D18A9856A87","full_name":"Payne, Pavel","first_name":"Pavel","last_name":"Payne"},{"first_name":"Pavel","last_name":"Plevka","full_name":"Plevka, Pavel"},{"orcid":"0000-0002-4624-4612","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P","first_name":"Jonathan P","last_name":"Bollback"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052"}],"scopus_import":"1","publication":"Molecular Biology and Evolution","external_id":{"pmid":["42827080"]},"dataavailabilitystatement":"The data underlying this article are available in the article and in its online material.","_id":"23090","acknowledgement":"We thank Stuart Baird, Nick Barton, Max Joesch, Meriem El Karoui, Mato Lagator, Ivana Mašlaňová, Stepan Ovchinnikov, Roman Pantůček, Maroš Pleška, Jitka Polechová, and Bryan Wu for their feedback on the manuscript. We are grateful to the Redlinger Hut for hosting many discussions about the project away from the daily buzz. We acknowledge the core facility CELLIM supported by the Czech-BioImaging large RI project (LM2023050 funded by MEYS CR) for their support. This work was supported by H2020 European Research Council EVOLHGT No. 648440 to JPB, European Commission Programme EXCELES project LX22NPO5103 “National Institute of Virology and Bacteriology” to PPl, and a bilateral Czech-Austrian mobility grant 8J3AT003 funded by MEYS CR and OeAD AT to PPa and CCG.","main_file_link":[{"url":"https://doi.org/10.1093/molbev/msag238","open_access":"1"}],"oa_version":"Published Version","status":"public","department":[{"_id":"CaGu"}],"has_accepted_license":"1","language":[{"iso":"eng"}],"month":"10","fulldoi":"https://doi.org/10.1093/molbev/msag238","abstract":[{"lang":"eng","text":"Homologous recombination is ubiquitous across evolution, generating variation through genetic reshuffling. Although bacteria lack meiotic recombination, homologous recombination has been known to extensively shape their genomes. However, the mechanisms and ecological conditions sustaining frequent recombination in bacteria remain unclear. Using an Escherichia coli–P1 phage model system, we reveal how frequent recombination emerges from CRISPR-based herd immunity to a generalized transducing phage (DNA vector). Herd immunity maintains phage-susceptible donor bacteria, recipient immune bacteria, and transducing phage, which promotes chromosomal gene flow that exceeds spontaneous mutation by up to two orders of magnitude. Notably, recombination begins as bacterial cultures enter stationary phase, when canonical mutation supply through population growth and DNA replication is strongly reduced, and recombination can be reinitiated by brief fresh nutrient pulses. Genetic analysis showed that stationary-phase recombination requires recA, recB, and recG, connecting this process to a defined homologous recombination pathway, and suggests a plausible transcriptional regulatory link to transition to nutrient limitation. Bacterial herd immunity therefore has an unexpected evolutionary consequence: it can promote homologous recombination by turning phages into de facto pollinators. This mechanism can help explain how high rates of homologous recombination may be sustained across bacterial populations and suggests that bacterial immune systems can shape molecular evolution not only by blocking infection but also by regulating genetic exchange."}],"day":"03","date_updated":"2026-10-12T10:51:54Z","date_created":"2026-10-11T22:02:04Z","volume":43,"DOAJ_listed":"1","tmp":{"short":"CC BY-NC (4.0)","image":"/images/cc_by_nc.png","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)"},"article_processing_charge":"Yes","type":"journal_article"},{"file":[{"access_level":"open_access","creator":"dernst","success":1,"file_id":"19295","checksum":"11a5bab307a4e1e1598a1577d8a2fbb5","date_updated":"2025-03-04T13:08:52Z","file_name":"Data1.xlsx","date_created":"2025-03-04T13:08:52Z","relation":"main_file","file_size":269054,"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet"},{"relation":"main_file","file_size":87143,"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","date_created":"2025-03-04T13:08:52Z","date_updated":"2025-03-04T13:08:52Z","file_name":"Data2.xlsx","success":1,"creator":"dernst","access_level":"open_access","checksum":"3b057894322639f0c1e11fb2e84173e6","file_id":"19296"},{"date_updated":"2025-03-04T13:08:52Z","file_name":"Data3.xlsx","success":1,"access_level":"open_access","creator":"dernst","checksum":"a551e1b79a138bb97ab96979aa475b3c","file_id":"19297","file_size":129101,"relation":"main_file","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","date_created":"2025-03-04T13:08:52Z"},{"date_created":"2025-03-04T13:08:52Z","file_size":86243,"relation":"main_file","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","access_level":"open_access","creator":"dernst","success":1,"file_id":"19298","checksum":"d6909c9bf111f859058082b1a2f970c4","date_updated":"2025-03-04T13:08:52Z","file_name":"Data4.xlsx"},{"access_level":"open_access","creator":"dernst","success":1,"file_id":"19299","checksum":"e5725a3a118a3f06846104906c8792c7","date_updated":"2025-03-04T13:08:52Z","file_name":"Data5.xlsx","date_created":"2025-03-04T13:08:52Z","file_size":26049,"relation":"main_file","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet"},{"file_size":7327253,"relation":"main_file","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","date_created":"2025-03-04T13:08:52Z","date_updated":"2025-03-04T13:08:52Z","file_name":"RawData_2_3.xlsx","creator":"dernst","access_level":"open_access","success":1,"file_id":"19300","checksum":"16763c127049f14bd587dc885677dce1"},{"file_id":"19301","checksum":"2f3e1a368b4e3abc46bf37e02724f0f4","creator":"dernst","access_level":"open_access","success":1,"file_name":"Readme.txt","date_updated":"2025-03-05T07:39:38Z","date_created":"2025-03-05T07:39:38Z","content_type":"text/plain","relation":"main_file","file_size":606}],"date_published":"2025-03-04T00:00:00Z","file_date_updated":"2025-03-05T07:39:38Z","publisher":"Institute of Science and Technology Austria","title":"Data for \"Pulsatile basal gene expression as a fitness determinant in bacteria\"","OA_type":"gold","oa":1,"related_material":{"record":[{"status":"public","id":"19626","relation":"used_in_publication"}]},"oa_version":"Published Version","_id":"19294","OA_place":"repository","author":[{"first_name":"Kirti","last_name":"Jain","full_name":"Jain, Kirti","id":"330F0278-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3809-0449"},{"orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert","first_name":"Robert","last_name":"Hauschild"},{"orcid":"0000-0003-1006-6639","last_name":"Bochkareva","first_name":"Olga","full_name":"Bochkareva, Olga","id":"C4558D3C-6102-11E9-A62E-F418E6697425"},{"full_name":"Römhild, Roderich","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","last_name":"Römhild","first_name":"Roderich","orcid":"0000-0001-9480-5261"},{"orcid":"0000-0002-6699-1455","first_name":"Gašper","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052"}],"day":"04","date_updated":"2026-05-20T08:33:07Z","corr_author":"1","fulldoi":"https://doi.org/10.15479/AT:ISTA:19294","citation":{"ista":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Data for ‘Pulsatile basal gene expression as a fitness determinant in bacteria’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:19294\">10.15479/AT:ISTA:19294</a>.","ieee":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet, “Data for ‘Pulsatile basal gene expression as a fitness determinant in bacteria.’” Institute of Science and Technology Austria, 2025.","apa":"Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., &#38; Guet, C. C. (2025). 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Data for “Pulsatile basal gene expression as a fitness determinant in bacteria.” 2025. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:19294\">10.15479/AT:ISTA:19294</a>","short":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, (2025)."},"abstract":[{"lang":"eng","text":"Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of non-functional “promoter leakiness”, merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the non-canonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g. control of costly-to-induce multi-drug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multi-drug resistance is crucial for effective public health measures."}],"has_accepted_license":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"03","status":"public","department":[{"_id":"CaGu"},{"_id":"Bio"},{"_id":"FyKo"},{"_id":"GaTk"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_processing_charge":"No","ddc":["570"],"type":"research_data","date_created":"2025-03-04T13:27:21Z","doi":"10.15479/AT:ISTA:19294","year":"2025"},{"OA_place":"publisher","isi":1,"oa":1,"related_material":{"link":[{"relation":"press_release","description":"News on ISTA website","url":"https://ista.ac.at/en/news/clockwork-just-for-antibiotic-resistance/"}],"record":[{"status":"public","id":"19294","relation":"research_data"}]},"project":[{"_id":"c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473","grant_number":"CZI01","name":"Tools for automation and feedback microscopy"},{"_id":"bd6f94d1-d553-11ed-ba76-ae9f07250f74","grant_number":"E219","name":"Non-canonical antibiotic interactions"},{"name":"Evolutionary analysis of gene regulation","_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181","grant_number":"I05127"}],"pmid":1,"article_number":"e2413709122","article_type":"original","file":[{"file_id":"19888","checksum":"115a687f40009660eb4b38b4f6559d41","creator":"dernst","access_level":"open_access","success":1,"file_name":"2025_PNAS_Jain.pdf","date_updated":"2025-06-24T07:27:43Z","date_created":"2025-06-24T07:27:43Z","content_type":"application/pdf","file_size":2949523,"relation":"main_file"}],"publisher":"National Academy of Sciences","issue":"15","OA_type":"hybrid","intvolume":"       122","quality_controlled":"1","ddc":["570"],"doi":"10.1073/pnas.2413709122","year":"2025","citation":{"short":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, Proceedings of the National Academy of Sciences 122 (2025).","ama":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Pulsatile basal gene expression as a fitness determinant in bacteria. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(15). doi:<a href=\"https://doi.org/10.1073/pnas.2413709122\">10.1073/pnas.2413709122</a>","mla":"Jain, Kirti, et al. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15, e2413709122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2413709122\">10.1073/pnas.2413709122</a>.","chicago":"Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper Tkačik, and Calin C Guet. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2413709122\">https://doi.org/10.1073/pnas.2413709122</a>.","ieee":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet, “Pulsatile basal gene expression as a fitness determinant in bacteria,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15. National Academy of Sciences, 2025.","apa":"Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., &#38; Guet, C. C. (2025). Pulsatile basal gene expression as a fitness determinant in bacteria. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2413709122\">https://doi.org/10.1073/pnas.2413709122</a>","ista":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Pulsatile basal gene expression as a fitness determinant in bacteria. Proceedings of the National Academy of Sciences. 122(15), e2413709122."},"APC_amount":"5949 EUR","publication_status":"published","corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"19626","acknowledgement":"K.J. thanks B. Wu, I. Tomanek, K. Tomasek for detailed discussions on the manuscript, all other members from the Guet laboratory for valuable feedback, R. Chait, & Imaging and Optics Facility, Institute of Science and Technology Austria for helping with microscopy, Dr. Sudha Rao and Dr. Raja Mugasimangalam, Genotypic Technology India for allowing time off to address the revisions. K.J. acknowledges Institute of Science and Technology fellowship IC1006FELL02, R.H. was supported in part by Chan Zuckerberg Initiative and Donor Advised-Fund grant 2020-225401 (https://doi.org/10.37921/120055ratwvi), O.O.B. acknowledges Fonds Zur Förderung der Wissenschaftlichen Forschung (FWF) Grant ESP253-B, R.R. acknowledges FWF Grant 10.55776/ESP219, C.C.G. acknowledges FWF I5127-B.","oa_version":"Published Version","scopus_import":"1","publication":"Proceedings of the National Academy of Sciences","author":[{"full_name":"Jain, Kirti","id":"330F0278-F248-11E8-B48F-1D18A9856A87","first_name":"Kirti","last_name":"Jain","orcid":"0000-0002-3809-0449"},{"orcid":"0000-0001-9843-3522","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","first_name":"Robert","full_name":"Hauschild, Robert"},{"orcid":"0000-0003-1006-6639","first_name":"Olga","last_name":"Bochkareva","id":"C4558D3C-6102-11E9-A62E-F418E6697425","full_name":"Bochkareva, Olga"},{"last_name":"Römhild","first_name":"Roderich","full_name":"Römhild, Roderich","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","orcid":"0000-0001-9480-5261"},{"orcid":"0000-0002-6699-1455","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","last_name":"Tkačik"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052"}],"external_id":{"isi":["001471235200001"],"pmid":["40193613"]},"date_published":"2025-04-15T00:00:00Z","file_date_updated":"2025-06-24T07:27:43Z","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"title":"Pulsatile basal gene expression as a fitness determinant in bacteria","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)"},"type":"journal_article","article_processing_charge":"Yes (in subscription journal)","date_created":"2025-04-27T22:02:13Z","volume":122,"fulldoi":"https://doi.org/10.1073/pnas.2413709122","abstract":[{"lang":"eng","text":"Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of nonfunctional “promoter leakiness,” merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the noncanonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g., control of costly-to-induce multidrug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multidrug resistance is crucial for effective public health measures."}],"date_updated":"2026-05-20T08:33:08Z","day":"15","department":[{"_id":"CaGu"},{"_id":"Bio"},{"_id":"FyKo"},{"_id":"GaTk"}],"status":"public","has_accepted_license":"1","acknowledged_ssus":[{"_id":"Bio"}],"month":"04","language":[{"iso":"eng"}]},{"file_date_updated":"2025-12-30T08:18:07Z","date_published":"2025-09-01T00:00:00Z","title":"A F420-dependent single domain chemogenetic tool for protein de-dimerization","publication_identifier":{"issn":["0022-2836"],"eissn":["1089-8638"]},"acknowledgement":"We thank J. Kaczmarski for advice on isothermal titration calorimetry and helpful comments, and Alexandra Tichy, Elliot Gerrard and Rahkesh T Sabapathy for assistance with experiments. This study was supported by grants of the Australian Research Council (FT200100519 and DP200102093, to H.J.; DE190100806, DP220101901, FT230100203, and DP250102939 to T.P.S.D.C; DP200102093, CE200100029 and CE200100012 to C.J.J.), the National Health and Medical Research Council (APP1187638, to H.J.). S.K. was supported by the graduate program MolecularDrugTargets (Austrian Science Fund FWF W1232). The Australian Regenerative Medicine Institute is supported by grants from the State Government of Victoria and the Australian Government. The EMBL Australia Partnership Laboratory (EMBL Australia) is supported by the National Collaborative Research Infrastructure Strategy (NCRIS) of the Australian Government. T.P.S.D.C. acknowledges the University of Adelaide for a Future Making Fellowship. E.R.R.M acknowledges the Grains Research and Development Corporation (9176977) for support through a PhD scholarship and operational funding. J.A. and E.R.R.M. were supported by Australian Research Training Program scholarship. MicroMon of Monash University provided Sanger sequencing services. Imaging was performed in the CellScreen SA screening center of Flinders University. C.J.J. thanks the ARC Centre of Excellence for Innovations in Peptide and Protein Science and the ARC Centre of Excellence in Synthetic Biology. We thank the staff of the MX2 beamline at the Australian Synchrotron, part of ANSTO, which made use of the Australian Cancer Research Foundation (ACRF) detector.","_id":"19725","oa_version":"Published Version","external_id":{"isi":["001494762800001"],"pmid":["40324743"]},"publication":"Journal of Molecular Biology","scopus_import":"1","author":[{"last_name":"Antoney","full_name":"Antoney, James","first_name":"James"},{"last_name":"Kainrath","first_name":"Stephanie","full_name":"Kainrath, Stephanie","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6709-2195"},{"full_name":"Dubowsky, Joshua G.","last_name":"Dubowsky","first_name":"Joshua G."},{"full_name":"Ahmed, F. Hafna","first_name":"F. Hafna","last_name":"Ahmed"},{"last_name":"Kang","first_name":"Suk Woo","full_name":"Kang, Suk Woo"},{"first_name":"Emily R.R.","last_name":"Mackie","full_name":"Mackie, Emily R.R."},{"first_name":"Gustavo","full_name":"Bracho Granado, Gustavo","last_name":"Bracho Granado"},{"first_name":"Tatiana P.","full_name":"Soares Da Costa, Tatiana P.","last_name":"Soares Da Costa"},{"first_name":"Colin J.","full_name":"Jackson, Colin J.","last_name":"Jackson"},{"orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","first_name":"Harald L","last_name":"Janovjak"}],"abstract":[{"text":"Protein-protein interactions (PPIs) mediate many fundamental cellular processes. Control of PPIs through optically or chemically responsive protein domains has had a profound impact on basic research and some clinical applications. Most chemogenetic methods induce the association, i.e., dimerization or oligomerization, of target proteins, whilst the few available dissociation approaches either break large oligomeric protein clusters or heteromeric complexes. Here, we have exploited the controlled dissociation of a homodimeric oxidoreductase from mycobacteria (MSMEG_2027) by its native cofactor, F420, which is not present in mammals, as a bioorthogonal monomerization switch. Using X-ray crystallography, we found that in the absence of F420 MSMEG_2027 forms a unique domain-swapped dimer that occludes the cofactor binding site. Rearrangement of the N-terminal helix upon F420 binding results in the dissolution of the dimer. We then showed that MSMEG_2027 can be fused to proteins of interest in human cells and applied it as a tool to induce and release MAPK/ERK signalling downstream of a chimeric fibroblast growth factor receptor 1 (FGFR1) tyrosine kinase. This F420-dependent chemogenetic de-homodimerization tool is stoichiometric and based on a single domain and thus represents a novel mechanism to investigate protein complexes in situ.","lang":"eng"}],"fulldoi":"https://doi.org/10.1016/j.jmb.2025.169184","date_updated":"2025-12-30T08:18:25Z","day":"01","department":[{"_id":"CaGu"}],"status":"public","month":"09","language":[{"iso":"eng"}],"has_accepted_license":"1","article_processing_charge":"Yes (in subscription journal)","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)"},"type":"journal_article","date_created":"2025-05-25T22:16:39Z","volume":437,"file":[{"content_type":"application/pdf","relation":"main_file","file_size":1682721,"date_created":"2025-12-30T08:18:07Z","file_name":"2025_JourMolecularBiology_Antoney.pdf","date_updated":"2025-12-30T08:18:07Z","checksum":"fb6e84ba7dc92faee97647fd2bc8cca8","file_id":"20892","success":1,"creator":"dernst","access_level":"open_access"}],"intvolume":"       437","OA_type":"hybrid","issue":"17","publisher":"Elsevier","OA_place":"publisher","isi":1,"oa":1,"project":[{"call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"255A6082-B435-11E9-9278-68D0E5697425"}],"pmid":1,"article_type":"original","article_number":"169184","publication_status":"published","citation":{"short":"J. Antoney, S. Kainrath, J.G. Dubowsky, F.H. Ahmed, S.W. Kang, E.R.R. Mackie, G. Bracho Granado, T.P. Soares Da Costa, C.J. Jackson, H.L. Janovjak, Journal of Molecular Biology 437 (2025).","ama":"Antoney J, Kainrath S, Dubowsky JG, et al. A F420-dependent single domain chemogenetic tool for protein de-dimerization. <i>Journal of Molecular Biology</i>. 2025;437(17). doi:<a href=\"https://doi.org/10.1016/j.jmb.2025.169184\">10.1016/j.jmb.2025.169184</a>","apa":"Antoney, J., Kainrath, S., Dubowsky, J. G., Ahmed, F. H., Kang, S. W., Mackie, E. R. R., … Janovjak, H. L. (2025). A F420-dependent single domain chemogenetic tool for protein de-dimerization. <i>Journal of Molecular Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jmb.2025.169184\">https://doi.org/10.1016/j.jmb.2025.169184</a>","ieee":"J. Antoney <i>et al.</i>, “A F420-dependent single domain chemogenetic tool for protein de-dimerization,” <i>Journal of Molecular Biology</i>, vol. 437, no. 17. Elsevier, 2025.","ista":"Antoney J, Kainrath S, Dubowsky JG, Ahmed FH, Kang SW, Mackie ERR, Bracho Granado G, Soares Da Costa TP, Jackson CJ, Janovjak HL. 2025. A F420-dependent single domain chemogenetic tool for protein de-dimerization. Journal of Molecular Biology. 437(17), 169184.","mla":"Antoney, James, et al. “A F420-Dependent Single Domain Chemogenetic Tool for Protein de-Dimerization.” <i>Journal of Molecular Biology</i>, vol. 437, no. 17, 169184, Elsevier, 2025, doi:<a href=\"https://doi.org/10.1016/j.jmb.2025.169184\">10.1016/j.jmb.2025.169184</a>.","chicago":"Antoney, James, Stephanie Kainrath, Joshua G. Dubowsky, F. Hafna Ahmed, Suk Woo Kang, Emily R.R. Mackie, Gustavo Bracho Granado, Tatiana P. Soares Da Costa, Colin J. Jackson, and Harald L Janovjak. “A F420-Dependent Single Domain Chemogenetic Tool for Protein de-Dimerization.” <i>Journal of Molecular Biology</i>. Elsevier, 2025. <a href=\"https://doi.org/10.1016/j.jmb.2025.169184\">https://doi.org/10.1016/j.jmb.2025.169184</a>."},"PlanS_conform":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"quality_controlled":"1","year":"2025","doi":"10.1016/j.jmb.2025.169184"},{"publisher":"The Royal Society","issue":"6","intvolume":"        21","OA_type":"hybrid","file":[{"date_created":"2025-06-23T11:34:39Z","file_size":1850797,"relation":"main_file","content_type":"application/pdf","success":1,"access_level":"open_access","creator":"dernst","checksum":"016f644ed068f8609ded306ad26dbd3f","file_id":"19873","date_updated":"2025-06-23T11:34:39Z","file_name":"2025_BiologyLetters_Nikolic.pdf"}],"article_number":"20250080","article_type":"original","pmid":1,"oa":1,"project":[{"call_identifier":"FP7","grant_number":"291734","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme"},{"call_identifier":"FWF","name":"Bacterial toxin-antitoxin systems as antiphage defense mechanisms","grant_number":"V00738","_id":"26956E74-B435-11E9-9278-68D0E5697425"}],"OA_place":"publisher","isi":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","corr_author":"1","citation":{"ama":"Nikolic N, Pleska M, Bergmiller T, Guet CC. A bacterial toxin-antitoxin system as a native defence element against RNA phages. <i>Biology Letters</i>. 2025;21(6). doi:<a href=\"https://doi.org/10.1098/rsbl.2025.0080\">10.1098/rsbl.2025.0080</a>","short":"N. Nikolic, M. Pleska, T. Bergmiller, C.C. Guet, Biology Letters 21 (2025).","apa":"Nikolic, N., Pleska, M., Bergmiller, T., &#38; Guet, C. C. (2025). A bacterial toxin-antitoxin system as a native defence element against RNA phages. <i>Biology Letters</i>. The Royal Society. <a href=\"https://doi.org/10.1098/rsbl.2025.0080\">https://doi.org/10.1098/rsbl.2025.0080</a>","ieee":"N. Nikolic, M. Pleska, T. Bergmiller, and C. C. Guet, “A bacterial toxin-antitoxin system as a native defence element against RNA phages,” <i>Biology Letters</i>, vol. 21, no. 6. The Royal Society, 2025.","ista":"Nikolic N, Pleska M, Bergmiller T, Guet CC. 2025. A bacterial toxin-antitoxin system as a native defence element against RNA phages. Biology Letters. 21(6), 20250080.","mla":"Nikolic, Nela, et al. “A Bacterial Toxin-Antitoxin System as a Native Defence Element against RNA Phages.” <i>Biology Letters</i>, vol. 21, no. 6, 20250080, The Royal Society, 2025, doi:<a href=\"https://doi.org/10.1098/rsbl.2025.0080\">10.1098/rsbl.2025.0080</a>.","chicago":"Nikolic, Nela, Maros Pleska, Tobias Bergmiller, and Calin C Guet. “A Bacterial Toxin-Antitoxin System as a Native Defence Element against RNA Phages.” <i>Biology Letters</i>. The Royal Society, 2025. <a href=\"https://doi.org/10.1098/rsbl.2025.0080\">https://doi.org/10.1098/rsbl.2025.0080</a>."},"publication_status":"published","ec_funded":1,"doi":"10.1098/rsbl.2025.0080","year":"2025","quality_controlled":"1","ddc":["570"],"publication_identifier":{"eissn":["1744-957X"],"issn":["1744-9561"]},"title":"A bacterial toxin-antitoxin system as a native defence element against RNA phages","date_published":"2025-06-11T00:00:00Z","file_date_updated":"2025-06-23T11:34:39Z","author":[{"orcid":"0000-0001-9068-6090","full_name":"Nikolic, Nela","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","last_name":"Nikolic","first_name":"Nela"},{"orcid":"0000-0001-7460-7479","last_name":"Pleska","first_name":"Maros","full_name":"Pleska, Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-5396-4346","last_name":"Bergmiller","full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","first_name":"Tobias"},{"orcid":"0000-0001-6220-2052","last_name":"Guet","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C"}],"publication":"Biology Letters","scopus_import":"1","external_id":{"pmid":["40494395"],"isi":["001505019800001"]},"oa_version":"Published Version","_id":"19857","acknowledgement":"This work was supported by ISTFELLOW (People Program – Marie Curie Actions of the European Union’s Seventh Framework Program FP7 under REA grant agreement 291734), the FWF (Austrian Science Fund) Elise Richter Program project number V 738 and the Wellcome Trust Institutional Strategic Support Award (WT105618MA), to N.N. M.P. was a Simons Foundation Fellow of the Life Sciences Research Foundation. We are grateful to Kathrin Tomasek, Lisa Butt, Chris Estell, Alys Jepson, Franklin Nobrega, Stefano Pagliara, Remy Chait, Steve West, Vicki Gold, Josh Eaton, Ivana Gudelj and Rob Beardmore for useful discussions and technical support, as well as to Robin Wright, Christian Fitch and Ben Temperton for sharing equipment. We thank Laurence Van Melderen for sharing the strains. We acknowledge the IST Austria Lab Support Facility, LSI Technical Services Team at the University of Exeter and the Translational Research Exchange @ Exeter (TREE) network. N.N. is grateful to Fabrice Gielen for his support.","has_accepted_license":"1","acknowledged_ssus":[{"_id":"LifeSc"}],"language":[{"iso":"eng"}],"month":"06","department":[{"_id":"CaGu"}],"status":"public","day":"11","date_updated":"2025-09-30T13:38:08Z","fulldoi":"https://doi.org/10.1098/rsbl.2025.0080","abstract":[{"text":"Bacteria have evolved a wide range of defence strategies to protect themselves against bacterial viruses (phages). Most known bacterial antiphage defence systems target phages with DNA genomes, which raises the question of how bacteria defend against phages with RNA genomes. Bacterial toxin–antitoxin systems that cleave intracellular RNA could potentially protect bacteria against RNA phages, but this has not been explored experimentally. In this study, we investigated the role of a model toxin–antitoxin system, MazEF, in protecting Escherichia coli against two RNA phage species. When challenged with these phages, the native presence of mazEF moderately reduced population susceptibility and increased the survival of individual E. coli cells. Genomic analysis further revealed an underrepresentation of the MazF cleavage site in genomes of RNA phages infecting E. coli, indicating selection against cleavage. These results show that, in addition to other physiological roles, RNA-degrading toxin–antitoxin systems may also help defend against RNA phages.","lang":"eng"}],"volume":21,"date_created":"2025-06-22T22:02:06Z","type":"journal_article","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 (via OA deal)"},{"day":"04","date_updated":"2026-05-20T07:53:03Z","fulldoi":"https://doi.org/10.3389/fpls.2025.1612366","abstract":[{"text":"Introduction: Acid-growth theory has been postulated in the 70s to explain the rapid elongation of plant cells in response to the hormone auxin. More recently, it has been demonstrated that activation of the proton ATPs pump (H+-ATPs) promoting acidification of the apoplast is the principal mechanism by which auxin and other hormones such as brassinosteroids (BR) induce cell elongation. Despite these advances, the impact of this acidification on the mechanical properties of the cell wall remained largely unexplored.\r\n\r\nMethods: Here, we use elongation assays of Arabidopsis thaliana hypocotyls and Atomic Force Microscopy (AFM) to correlate hormone-induced tissue elongation and local changes in cell wall mechanical properties. Furthermore, employing transgenic lines over-expressing Pectin Methyl Esterase (PME), along with calcium chelators, we investigate the effect of pectin modification in hormone-driven cell elongation.\r\n\r\nResults: We demonstrate that acidification of apoplast is necessary and sufficient to induce cell elongation through promoting cell wall softening. Moreover, we show that enhanced PME activity can induce both cell wall softening or stiffening in extracellular calcium dependent-manner and that tight control of PME activity is required for proper hypocotyl elongation.\r\n\r\nDiscussion: Our results confirm a dual role of PME in plant cell elongation. However, further investigation is needed to assess the status of pectin following short- or long-term PME treatments in order to determine if pectin methyl-esterification might promote its degradation as well as the role of PME inhibitors upon PME induction.","lang":"eng"}],"has_accepted_license":"1","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"E-Lib"}],"language":[{"iso":"eng"}],"month":"07","department":[{"_id":"EdHa"},{"_id":"EvBe"},{"_id":"CaGu"}],"status":"public","type":"journal_article","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","DOAJ_listed":"1","volume":16,"date_created":"2025-07-27T22:01:26Z","date_published":"2025-07-04T00:00:00Z","file_date_updated":"2025-07-31T07:28:54Z","publication_identifier":{"eissn":["1664-462X"]},"title":"Dual role of pectin methyl esterase activity in the regulation of plant cell wall biophysical properties","oa_version":"Published Version","_id":"20080","acknowledgement":"The author(s) declare that financial support was received for the research and/or publication of this article. This work was supported by grants from the European Research Council (Starting Independent Research Grant ERC-2007-Stg- 207362-HCPO to EB) and MG was recipient of an IST Interdisciplinary project (IC1022IPC03).\r\nWe acknowledge Jaume F. Martı́nez Garcı́a for phyAphyB mutant seeds. We acknowledge CF Nanobiotechnology of CIISB, Instruct-CZ Centre, supported by MEYS CR (LM2018127). We gratefully acknowledge support by the Scientific Service Units at ISTA, including the Imaging and Optics and Lab Support facilities and Library. We thank Stefan Riegler for the efforts to establish immunodetection method.","publication":"Frontiers in Plant Science","scopus_import":"1","author":[{"first_name":"Marçal","full_name":"Gallemi, Marçal","last_name":"Gallemi","id":"460C6802-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4675-6893"},{"orcid":"0000-0001-9179-6099","full_name":"Montesinos López, Juan C","id":"310A8E3E-F248-11E8-B48F-1D18A9856A87","first_name":"Juan C","last_name":"Montesinos López"},{"first_name":"Nikola","id":"18e95355-e05a-11ea-a9c0-8fba1b89e83a","last_name":"Zarevski","full_name":"Zarevski, Nikola"},{"full_name":"Pribyl, Jan","first_name":"Jan","last_name":"Pribyl"},{"first_name":"Petr","full_name":"Skládal, Petr","last_name":"Skládal"},{"orcid":"0000-0001-6005-1561","first_name":"Edouard B","last_name":"Hannezo","full_name":"Hannezo, Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Eva","full_name":"Benková, Eva","id":"38F4F166-F248-11E8-B48F-1D18A9856A87","last_name":"Benková","orcid":"0000-0002-8510-9739"}],"external_id":{"isi":["001530690900001"],"pmid":["40688689"]},"PlanS_conform":"1","corr_author":"1","APC_amount":"3642,79 EUR","citation":{"ama":"Gallemi M, Montesinos López JC, Zarevski N, et al. Dual role of pectin methyl esterase activity in the regulation of plant cell wall biophysical properties. <i>Frontiers in Plant Science</i>. 2025;16. doi:<a href=\"https://doi.org/10.3389/fpls.2025.1612366\">10.3389/fpls.2025.1612366</a>","short":"M. Gallemi, J.C. Montesinos López, N. Zarevski, J. Pribyl, P. Skládal, E.B. Hannezo, E. Benková, Frontiers in Plant Science 16 (2025).","mla":"Gallemi, Marçal, et al. “Dual Role of Pectin Methyl Esterase Activity in the Regulation of Plant Cell Wall Biophysical Properties.” <i>Frontiers in Plant Science</i>, vol. 16, 1612366, Frontiers Media, 2025, doi:<a href=\"https://doi.org/10.3389/fpls.2025.1612366\">10.3389/fpls.2025.1612366</a>.","chicago":"Gallemi, Marçal, Juan C Montesinos López, Nikola Zarevski, Jan Pribyl, Petr Skládal, Edouard B Hannezo, and Eva Benková. “Dual Role of Pectin Methyl Esterase Activity in the Regulation of Plant Cell Wall Biophysical Properties.” <i>Frontiers in Plant Science</i>. Frontiers Media, 2025. <a href=\"https://doi.org/10.3389/fpls.2025.1612366\">https://doi.org/10.3389/fpls.2025.1612366</a>.","ieee":"M. Gallemi <i>et al.</i>, “Dual role of pectin methyl esterase activity in the regulation of plant cell wall biophysical properties,” <i>Frontiers in Plant Science</i>, vol. 16. Frontiers Media, 2025.","apa":"Gallemi, M., Montesinos López, J. C., Zarevski, N., Pribyl, J., Skládal, P., Hannezo, E. B., &#38; Benková, E. (2025). Dual role of pectin methyl esterase activity in the regulation of plant cell wall biophysical properties. <i>Frontiers in Plant Science</i>. Frontiers Media. <a href=\"https://doi.org/10.3389/fpls.2025.1612366\">https://doi.org/10.3389/fpls.2025.1612366</a>","ista":"Gallemi M, Montesinos López JC, Zarevski N, Pribyl J, Skládal P, Hannezo EB, Benková E. 2025. Dual role of pectin methyl esterase activity in the regulation of plant cell wall biophysical properties. Frontiers in Plant Science. 16, 1612366."},"publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","ddc":["580"],"ec_funded":1,"year":"2025","doi":"10.3389/fpls.2025.1612366","file":[{"relation":"main_file","file_size":3665187,"content_type":"application/pdf","date_created":"2025-07-31T07:28:54Z","date_updated":"2025-07-31T07:28:54Z","file_name":"2025_FrontiersPlantSc_Gallemi.pdf","success":1,"creator":"dernst","access_level":"open_access","checksum":"9e6b8b53ba56d4a24a9bd91cf6d2dc58","file_id":"20093"}],"publisher":"Frontiers Media","intvolume":"        16","OA_type":"gold","oa":1,"project":[{"call_identifier":"FP7","_id":"253FCA6A-B435-11E9-9278-68D0E5697425","grant_number":"207362","name":"Hormonal cross-talk in plant organogenesis"},{"name":"IST Austria Open Access Fund","_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854"}],"OA_place":"publisher","isi":1,"article_number":"1612366","article_type":"original","pmid":1},{"corr_author":"1","researchdata_availability":"upon request","citation":{"mla":"Grah, Rok, et al. “Linking Molecular Mechanisms to Their Evolutionary Consequences: A Primer.” <i>Genetics</i>, vol. 229, no. 2, iyae191, Oxford University Press, 2025, doi:<a href=\"https://doi.org/10.1093/genetics/iyae191\">10.1093/genetics/iyae191</a>.","chicago":"Grah, Rok, Calin C Guet, Gašper Tkačik, and Mato Lagator. “Linking Molecular Mechanisms to Their Evolutionary Consequences: A Primer.” <i>Genetics</i>. Oxford University Press, 2025. <a href=\"https://doi.org/10.1093/genetics/iyae191\">https://doi.org/10.1093/genetics/iyae191</a>.","ieee":"R. Grah, C. C. Guet, G. Tkačik, and M. Lagator, “Linking molecular mechanisms to their evolutionary consequences: a primer,” <i>Genetics</i>, vol. 229, no. 2. Oxford University Press, 2025.","apa":"Grah, R., Guet, C. C., Tkačik, G., &#38; Lagator, M. (2025). Linking molecular mechanisms to their evolutionary consequences: a primer. <i>Genetics</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/genetics/iyae191\">https://doi.org/10.1093/genetics/iyae191</a>","ista":"Grah R, Guet CC, Tkačik G, Lagator M. 2025. Linking molecular mechanisms to their evolutionary consequences: a primer. Genetics. 229(2), iyae191.","ama":"Grah R, Guet CC, Tkačik G, Lagator M. Linking molecular mechanisms to their evolutionary consequences: a primer. <i>Genetics</i>. 2025;229(2). doi:<a href=\"https://doi.org/10.1093/genetics/iyae191\">10.1093/genetics/iyae191</a>","short":"R. Grah, C.C. Guet, G. Tkačik, M. Lagator, Genetics 229 (2025)."},"publication_status":"published","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","quality_controlled":"1","ddc":["570"],"doi":"10.1093/genetics/iyae191","year":"2025","file":[{"date_created":"2025-04-16T09:41:04Z","content_type":"application/pdf","relation":"main_file","file_size":1511688,"file_id":"19580","checksum":"f730e416795969449ef49d97b82ac494","access_level":"open_access","creator":"dernst","success":1,"file_name":"2025_Genetics_Grah.pdf","date_updated":"2025-04-16T09:41:04Z"}],"issue":"2","publisher":"Oxford University Press","OA_type":"hybrid","intvolume":"       229","oa":1,"das_tickbox":"1","isi":1,"OA_place":"publisher","supplementarymaterial":"yes","article_number":"iyae191","article_type":"original","pmid":1,"day":"01","date_updated":"2026-10-01T08:30:12Z","fulldoi":"https://doi.org/10.1093/genetics/iyae191","abstract":[{"lang":"eng","text":"A major obstacle to predictive understanding of evolution stems from the complexity of biological systems, which prevents detailed characterization of key evolutionary properties. Here, we highlight some of the major sources of complexity that arise when relating molecular mechanisms to their evolutionary consequences and ask whether accounting for every mechanistic detail is important to accurately predict evolutionary outcomes. To do this, we developed a mechanistic model of a bacterial promoter regulated by 2 proteins, allowing us to connect any promoter genotype to 6 phenotypes that capture the dynamics of gene expression following an environmental switch. Accounting for the mechanisms that govern how this system works enabled us to provide an in-depth picture of how regulated bacterial promoters might evolve. More importantly, we used the model to explore which factors that contribute to the complexity of this system are essential for understanding its evolution, and which can be simplified without information loss. We found that several key evolutionary properties—the distribution of phenotypic and fitness effects of mutations, the evolutionary trajectories during selection for regulation—can be accurately captured without accounting for all, or even most, parameters of the system. Our findings point to the need for a mechanistic approach to studying evolution, as it enables tackling biological complexity and in doing so improves the ability to predict evolutionary outcomes."}],"has_accepted_license":"1","month":"02","language":[{"iso":"eng"}],"department":[{"_id":"CaGu"},{"_id":"GaTk"}],"status":"public","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 (in subscription journal)","type":"journal_article","date_created":"2025-01-29T08:21:35Z","volume":229,"date_published":"2025-02-01T00:00:00Z","file_date_updated":"2025-04-16T09:41:04Z","publication_identifier":{"eissn":["1943-2631"]},"title":"Linking molecular mechanisms to their evolutionary consequences: a primer","oa_version":"Published Version","dataavailabilitystatement":"Strains and plasmids are available upon request. All experimental raw data can be found in Supplementary Data 1. All code underpinning this work is available at https://github.com/Lagator-Group/Linking-Molecular-Mechanisms-to-their-Evolutionary-consequence-a-primer or upon request.  Supplemental material available at GENETICS online","_id":"18936","acknowledgement":"The authors thank Nick Barton, Stepan Denisov, Claudia Igler, Srdjan Sarikas, Anna Staron, and the anonymous reviewers for useful comments and discussions that helped improve our work.\r\nFunding for this work was provided by the Wellcome Trust–Royal Society Sir Henry Dale Fellowship (216779/Z/19/Z) and the Royal Society Research Grant (RG\\R2\\232522) to M.L.","scopus_import":"1","author":[{"id":"483E70DE-F248-11E8-B48F-1D18A9856A87","last_name":"Grah","full_name":"Grah, Rok","first_name":"Rok","orcid":"0000-0003-2539-3560"},{"orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","last_name":"Tkačik","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Lagator","first_name":"Mato","full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87"}],"publication":"Genetics","external_id":{"pmid":["39601269"],"isi":["001379194200001"]}},{"publisher":"Institute of Science and Technology Austria","file":[{"relation":"source_file","file_size":10603235,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_created":"2025-10-21T17:33:27Z","embargo_to":"open_access","date_updated":"2026-04-30T22:30:02Z","file_name":"2025_Wu_Bryan_Thesis.docx","access_level":"closed","creator":"brwu","checksum":"d32ea83f259f6b0506325cd57b1d44c3","file_id":"20516"},{"embargo":"2026-04-30","content_type":"application/pdf","file_size":6251936,"relation":"main_file","date_created":"2025-10-21T17:33:26Z","file_name":"2025_Wu_Bryan_Thesis.pdf","date_updated":"2026-04-30T22:30:02Z","file_id":"20517","checksum":"53590046fd3244c5550b4022282449d2","access_level":"open_access","creator":"brwu"}],"alternative_title":["ISTA Thesis"],"OA_place":"publisher","oa":1,"supervisor":[{"full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"chicago":"Wu, Bryan. “An Examination on Phages as a Naturally Composable System.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-20470\">https://doi.org/10.15479/AT-ISTA-20470</a>.","mla":"Wu, Bryan. <i>An Examination on Phages as a Naturally Composable System</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20470\">10.15479/AT-ISTA-20470</a>.","ista":"Wu B. 2025. An examination on phages as a naturally composable system. Institute of Science and Technology Austria.","apa":"Wu, B. (2025). <i>An examination on phages as a naturally composable system</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-20470\">https://doi.org/10.15479/AT-ISTA-20470</a>","ieee":"B. Wu, “An examination on phages as a naturally composable system,” Institute of Science and Technology Austria, 2025.","ama":"Wu B. An examination on phages as a naturally composable system. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20470\">10.15479/AT-ISTA-20470</a>","short":"B. Wu, An Examination on Phages as a Naturally Composable System, Institute of Science and Technology Austria, 2025."},"publication_status":"published","corr_author":"1","page":"102","doi":"10.15479/AT-ISTA-20470","year":"2025","degree_awarded":"PhD","ddc":["579"],"publication_identifier":{"issn":["2663-337X"]},"title":"An examination on phages as a naturally composable system","date_published":"2025-10-30T00:00:00Z","file_date_updated":"2026-04-30T22:30:02Z","author":[{"id":"3C521EBA-F248-11E8-B48F-1D18A9856A87","full_name":"Wu, Bryan","last_name":"Wu","first_name":"Bryan"}],"_id":"20470","oa_version":"Published Version","status":"public","department":[{"_id":"GradSch"},{"_id":"CaGu"}],"has_accepted_license":"1","language":[{"iso":"eng"}],"month":"10","fulldoi":"https://doi.org/10.15479/AT-ISTA-20470","abstract":[{"lang":"eng","text":"Systems design has classically relied on composable systems, in which individual subsystems\r\nhave defined inputs, outputs, and interactions with each other; however, attempts at\r\ndesigning complex systems in synthetic biology has often run in to issues of crosstalk and\r\ninterference, given that these systems must function within the context of the host. In nature,\r\nmobile genetic elements are systems that have evolved to travel between hosts, and thus\r\nappear to be a good candidate with which to evaluate composability. Selecting temperate\r\nphages as a model system, I used mathematical modelling to identify sources of information\r\nthat temperate phages should respond to. I found that essential proteins of temperate phages\r\ncan interfere with potential hosts, indicating limitations to composability. I also designed a\r\nlysogeny reporter construct and characterize its behavior across various laboratory and\r\nenvironmental strains, finding differences in phage lambda lysogens, and potential\r\ninterference from prophages that already exist within the environmental strains. Although\r\nthe information gathered is not conclusive, it suggests that composability is not a key property\r\nof temperate phages, implying that biological systems may not be composable, and that other\r\nsystem design principles should be considered when designing synthetic systems."}],"date_updated":"2026-05-06T08:01:28Z","day":"30","date_created":"2025-10-15T13:30:21Z","article_processing_charge":"No","type":"dissertation"},{"pmid":1,"article_type":"original","supplementarymaterial":"unclear","isi":1,"project":[{"name":"Bacterial cytoplasm glass transition: passive physiological switch or active survival strategy","_id":"eb872896-77a9-11ec-83b8-f59a38ec17f8","grant_number":"ALTF 44-2021"}],"das_tickbox":"0","oa":1,"intvolume":"        53","publisher":"Annual Reviews","file":[{"date_updated":"2024-07-29T10:56:01Z","file_name":"2024_AnnualReviewBiophys_Lo.pdf","success":1,"creator":"dernst","access_level":"open_access","checksum":"e0505553b3cee624fa865f0cc5a99ecc","file_id":"17339","file_size":1276645,"relation":"main_file","content_type":"application/pdf","date_created":"2024-07-29T10:56:01Z"}],"year":"2024","doi":"10.1146/annurev-biophys-030822-032215","page":"487-510","ddc":["570"],"quality_controlled":"1","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","publication_status":"published","citation":{"ama":"Lo WC, Krasnopeeva E, Pilizota T. Bacterial Electrophysiology. <i>Annual Review of Biophysics</i>. 2024;53:487-510. doi:<a href=\"https://doi.org/10.1146/annurev-biophys-030822-032215\">10.1146/annurev-biophys-030822-032215</a>","short":"W.C. Lo, E. Krasnopeeva, T. Pilizota, Annual Review of Biophysics 53 (2024) 487–510.","chicago":"Lo, Wei Chang, Ekaterina Krasnopeeva, and Teuta Pilizota. “Bacterial Electrophysiology.” <i>Annual Review of Biophysics</i>. Annual Reviews, 2024. <a href=\"https://doi.org/10.1146/annurev-biophys-030822-032215\">https://doi.org/10.1146/annurev-biophys-030822-032215</a>.","mla":"Lo, Wei Chang, et al. “Bacterial Electrophysiology.” <i>Annual Review of Biophysics</i>, vol. 53, Annual Reviews, 2024, pp. 487–510, doi:<a href=\"https://doi.org/10.1146/annurev-biophys-030822-032215\">10.1146/annurev-biophys-030822-032215</a>.","ista":"Lo WC, Krasnopeeva E, Pilizota T. 2024. Bacterial Electrophysiology. Annual Review of Biophysics. 53, 487–510.","apa":"Lo, W. C., Krasnopeeva, E., &#38; Pilizota, T. (2024). Bacterial Electrophysiology. <i>Annual Review of Biophysics</i>. Annual Reviews. <a href=\"https://doi.org/10.1146/annurev-biophys-030822-032215\">https://doi.org/10.1146/annurev-biophys-030822-032215</a>","ieee":"W. C. Lo, E. Krasnopeeva, and T. Pilizota, “Bacterial Electrophysiology,” <i>Annual Review of Biophysics</i>, vol. 53. Annual Reviews, pp. 487–510, 2024."},"researchdata_availability":"no","external_id":{"isi":["001278237500021"],"pmid":["38382113"]},"author":[{"last_name":"Lo","full_name":"Lo, Wei Chang","first_name":"Wei Chang"},{"first_name":"Ekaterina","full_name":"Krasnopeeva, Ekaterina","id":"1F1EE44A-BF83-11EA-B3C1-BB9CC619BF3A","last_name":"Krasnopeeva"},{"first_name":"Teuta","last_name":"Pilizota","full_name":"Pilizota, Teuta"}],"publication":"Annual Review of Biophysics","scopus_import":"1","acknowledgement":"We would like to thank all members of the Pilizota lab, as well as Calin Guet, Orkun Soyer, Munehiro Asally, Peter Swain, and in particular Matt Scott and Ariel Amir, for their support, comments, and useful discussions. T.P. and W.-C.L. were supported by the Leverhulme Trust, grant RPG-2019-187, and T.P. is supported by EPSRC Fellowship EP/V03264X/1. E.K. was supported by a European Molecular Biology Organization Long-Term Postdoctoral Fellowship, ALTF 44-2021.","_id":"17325","oa_version":"Published Version","title":"Bacterial Electrophysiology","publication_identifier":{"issn":["1936-122X"],"eissn":["1936-1238"]},"file_date_updated":"2024-07-29T10:56:01Z","date_published":"2024-07-01T00:00:00Z","volume":53,"date_created":"2024-07-28T22:01:09Z","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)"},"type":"journal_article","article_processing_charge":"Yes (in subscription journal)","department":[{"_id":"CaGu"}],"status":"public","language":[{"iso":"eng"}],"month":"07","has_accepted_license":"1","abstract":[{"lang":"eng","text":"Bacterial ion fluxes are involved in the generation of energy, transport, and motility. As such, bacterial electrophysiology is fundamentally important for the bacterial life cycle, but it is often neglected and consequently, by and large, not understood. Arguably, the two main reasons for this are the complexity of measuring relevant variables in small cells with a cell envelope that contains the cell wall and the fact that, in a unicellular organism, relevant variables become intertwined in a nontrivial manner. To help give bacterial electrophysiology studies a firm footing, in this review, we go back to basics. We look first at the biophysics of bacterial membrane potential, and then at the approaches and models developed mostly for the study of neurons and eukaryotic mitochondria. We discuss their applicability to bacterial cells. Finally, we connect bacterial membrane potential with other relevant (electro)physiological variables and summarize methods that can be used to both measure and influence bacterial electrophysiology."}],"fulldoi":"https://doi.org/10.1146/annurev-biophys-030822-032215","day":"01","date_updated":"2026-10-01T08:29:37Z"},{"article_number":"1049255","article_type":"original","pmid":1,"oa":1,"isi":1,"publisher":"Frontiers","intvolume":"        14","file":[{"content_type":"application/pdf","file_size":6452841,"relation":"main_file","date_created":"2023-07-31T07:16:34Z","file_name":"2023_FrontiersMicrobiology_Guet.pdf","date_updated":"2023-07-31T07:16:34Z","file_id":"13322","checksum":"7dd322347512afaa5daf72a0154f2f07","creator":"dernst","access_level":"open_access","success":1}],"doi":"10.3389/fmicb.2023.1049255","year":"2023","quality_controlled":"1","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","corr_author":"1","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>","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.","ista":"Guet CC, Bruneaux L, Oikonomou P, Aldana M, Cluzel P. 2023. Monitoring lineages of growing and dividing bacteria reveals an inducible memory of <i>mar</i> operon expression. Frontiers in Microbiology. 14, 1049255.","mla":"Guet, Calin C., et al. “Monitoring Lineages of Growing and Dividing Bacteria Reveals an Inducible Memory of <i>Mar</i> Operon Expression.” <i>Frontiers in Microbiology</i>, vol. 14, 1049255, Frontiers, 2023, doi:<a href=\"https://doi.org/10.3389/fmicb.2023.1049255\">10.3389/fmicb.2023.1049255</a>.","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>.","short":"C.C. Guet, L. Bruneaux, P. Oikonomou, M. Aldana, P. Cluzel, Frontiers in Microbiology 14 (2023).","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>"},"publication_status":"published","scopus_import":"1","publication":"Frontiers in Microbiology","author":[{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052"},{"last_name":"Bruneaux","first_name":"L","full_name":"Bruneaux, L"},{"full_name":"Oikonomou, P","first_name":"P","last_name":"Oikonomou"},{"full_name":"Aldana, M","first_name":"M","last_name":"Aldana"},{"full_name":"Cluzel, P","last_name":"Cluzel","first_name":"P"}],"external_id":{"pmid":["37485524"],"isi":["001030002600001"]},"oa_version":"Published Version","_id":"12478","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.","publication_identifier":{"eissn":["1664-302X"]},"title":"Monitoring lineages of growing and dividing bacteria reveals an inducible memory of <i>mar</i> operon expression","date_published":"2023-06-20T00:00:00Z","file_date_updated":"2023-07-31T07:16:34Z","volume":14,"date_created":"2023-02-02T08:13:28Z","type":"journal_article","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","has_accepted_license":"1","month":"06","language":[{"iso":"eng"}],"status":"public","department":[{"_id":"CaGu"}],"day":"20","date_updated":"2024-10-09T21:03:59Z","fulldoi":"https://doi.org/10.3389/fmicb.2023.1049255","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"}]},{"department":[{"_id":"CaGu"}],"status":"public","month":"03","language":[{"iso":"eng"}],"has_accepted_license":"1","abstract":[{"lang":"eng","text":"Understanding and characterising biochemical processes inside single cells requires experimental platforms that allow one to perturb and observe the dynamics of such processes as well as computational methods to build and parameterise models from the collected data. Recent progress with experimental platforms and optogenetics has made it possible to expose each cell in an experiment to an individualised input and automatically record cellular responses over days with fine time resolution. However, methods to infer parameters of stochastic kinetic models from single-cell longitudinal data have generally been developed under the assumption that experimental data is sparse and that responses of cells to at most a few different input perturbations can be observed. Here, we investigate and compare different approaches for calculating parameter likelihoods of single-cell longitudinal data based on approximations of the chemical master equation (CME) with a particular focus on coupling the linear noise approximation (LNA) or moment closure methods to a Kalman filter. We show that, as long as cells are measured sufficiently frequently, coupling the LNA to a Kalman filter allows one to accurately approximate likelihoods and to infer model parameters from data even in cases where the LNA provides poor approximations of the CME. Furthermore, the computational cost of filtering-based iterative likelihood evaluation scales advantageously in the number of measurement times and different input perturbations and is thus ideally suited for data obtained from modern experimental platforms. To demonstrate the practical usefulness of these results, we perform an experiment in which single cells, equipped with an optogenetic gene expression system, are exposed to various different light-input sequences and measured at several hundred time points and use parameter inference based on iterative likelihood evaluation to parameterise a stochastic model of the system."}],"fulldoi":"https://doi.org/10.1371/journal.pcbi.1009950","date_updated":"2025-09-09T14:29:53Z","day":"18","date_created":"2022-04-03T22:01:42Z","volume":18,"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)"},"type":"journal_article","article_processing_charge":"No","title":"Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level","publication_identifier":{"eissn":["1553-7358"],"issn":["1553-734X"]},"file_date_updated":"2022-04-04T10:14:39Z","date_published":"2022-03-18T00:00:00Z","external_id":{"isi":["001044208400004"],"pmid":["35303737"]},"author":[{"first_name":"Anđela","full_name":"Davidović, Anđela","last_name":"Davidović"},{"orcid":"0000-0003-0876-3187","full_name":"Chait, Remy P","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","first_name":"Remy P","last_name":"Chait"},{"full_name":"Batt, Gregory","last_name":"Batt","first_name":"Gregory"},{"orcid":"0000-0003-1615-3282","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","first_name":"Jakob","last_name":"Ruess","full_name":"Ruess, Jakob"}],"publication":"PLoS Computational Biology","scopus_import":"1","acknowledgement":"We thank Virgile Andreani for useful discussions about the model and parameter inference. We thank Johan Paulsson and Jeffrey J Tabor for kind gifts of plasmids. R was supported by the ANR grant CyberCircuits (ANR-18-CE91-0002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","_id":"10939","oa_version":"Published Version","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","publication_status":"published","citation":{"ieee":"A. Davidović, R. P. Chait, G. Batt, and J. Ruess, “Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level,” <i>PLoS Computational Biology</i>, vol. 18, no. 3. Public Library of Science, 2022.","apa":"Davidović, A., Chait, R. P., Batt, G., &#38; Ruess, J. (2022). Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level. <i>PLoS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1009950\">https://doi.org/10.1371/journal.pcbi.1009950</a>","ista":"Davidović A, Chait RP, Batt G, Ruess J. 2022. Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level. PLoS Computational Biology. 18(3), e1009950.","mla":"Davidović, Anđela, et al. “Parameter Inference for Stochastic Biochemical Models from Perturbation Experiments Parallelised at the Single Cell Level.” <i>PLoS Computational Biology</i>, vol. 18, no. 3, e1009950, Public Library of Science, 2022, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1009950\">10.1371/journal.pcbi.1009950</a>.","chicago":"Davidović, Anđela, Remy P Chait, Gregory Batt, and Jakob Ruess. “Parameter Inference for Stochastic Biochemical Models from Perturbation Experiments Parallelised at the Single Cell Level.” <i>PLoS Computational Biology</i>. Public Library of Science, 2022. <a href=\"https://doi.org/10.1371/journal.pcbi.1009950\">https://doi.org/10.1371/journal.pcbi.1009950</a>.","ama":"Davidović A, Chait RP, Batt G, Ruess J. Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level. <i>PLoS Computational Biology</i>. 2022;18(3). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1009950\">10.1371/journal.pcbi.1009950</a>","short":"A. Davidović, R.P. Chait, G. Batt, J. Ruess, PLoS Computational Biology 18 (2022)."},"doi":"10.1371/journal.pcbi.1009950","year":"2022","ddc":["570","000"],"quality_controlled":"1","intvolume":"        18","issue":"3","publisher":"Public Library of Science","file":[{"file_name":"2022_PLoSCompBio_Davidovic.pdf","date_updated":"2022-04-04T10:14:39Z","file_id":"10947","checksum":"458ef542761fb714ced214f240daf6b2","creator":"dernst","access_level":"open_access","success":1,"content_type":"application/pdf","relation":"main_file","file_size":2958642,"date_created":"2022-04-04T10:14:39Z"}],"pmid":1,"article_type":"original","article_number":"e1009950","isi":1,"oa":1,"related_material":{"link":[{"relation":"software","url":"https://gitlab.pasteur.fr/adavidov/inferencelnakf"}]}},{"article_type":"original","article_number":"385","pmid":1,"oa":1,"isi":1,"intvolume":"         5","publisher":"Springer Nature","file":[{"file_name":"2022_CommBiology_Glover.pdf","date_updated":"2022-05-02T06:26:26Z","file_id":"11342","checksum":"7c6f76ab17393d650825cc240edc84b3","access_level":"open_access","creator":"dernst","success":1,"content_type":"application/pdf","file_size":2827723,"relation":"main_file","date_created":"2022-05-02T06:26:26Z"}],"year":"2022","doi":"10.1038/s42003-022-03336-6","ddc":["570"],"quality_controlled":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication_status":"published","citation":{"short":"G. Glover, M. Voliotis, U. Łapińska, B.M. Invergo, D. Soanes, P. O’Neill, K. Moore, N. Nikolic, P. Petrov, D.S. Milner, S. Roy, K. Heesom, T.A. Richards, K. Tsaneva-Atanasova, S. Pagliara, Communications Biology 5 (2022).","ama":"Glover G, Voliotis M, Łapińska U, et al. Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells. <i>Communications Biology</i>. 2022;5. doi:<a href=\"https://doi.org/10.1038/s42003-022-03336-6\">10.1038/s42003-022-03336-6</a>","ista":"Glover G, Voliotis M, Łapińska U, Invergo BM, Soanes D, O’Neill P, Moore K, Nikolic N, Petrov P, Milner DS, Roy S, Heesom K, Richards TA, Tsaneva-Atanasova K, Pagliara S. 2022. Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells. Communications Biology. 5, 385.","apa":"Glover, G., Voliotis, M., Łapińska, U., Invergo, B. M., Soanes, D., O’Neill, P., … Pagliara, S. (2022). Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells. <i>Communications Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s42003-022-03336-6\">https://doi.org/10.1038/s42003-022-03336-6</a>","ieee":"G. Glover <i>et al.</i>, “Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells,” <i>Communications Biology</i>, vol. 5. Springer Nature, 2022.","chicago":"Glover, Georgina, Margaritis Voliotis, Urszula Łapińska, Brandon M. Invergo, Darren Soanes, Paul O’Neill, Karen Moore, et al. “Nutrient and Salt Depletion Synergistically Boosts Glucose Metabolism in Individual Escherichia Coli Cells.” <i>Communications Biology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s42003-022-03336-6\">https://doi.org/10.1038/s42003-022-03336-6</a>.","mla":"Glover, Georgina, et al. “Nutrient and Salt Depletion Synergistically Boosts Glucose Metabolism in Individual Escherichia Coli Cells.” <i>Communications Biology</i>, vol. 5, 385, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s42003-022-03336-6\">10.1038/s42003-022-03336-6</a>."},"external_id":{"pmid":["35444215"],"isi":["000784143400001"]},"scopus_import":"1","author":[{"first_name":"Georgina","last_name":"Glover","full_name":"Glover, Georgina"},{"last_name":"Voliotis","full_name":"Voliotis, Margaritis","first_name":"Margaritis"},{"first_name":"Urszula","full_name":"Łapińska, Urszula","last_name":"Łapińska"},{"full_name":"Invergo, Brandon M.","first_name":"Brandon M.","last_name":"Invergo"},{"last_name":"Soanes","first_name":"Darren","full_name":"Soanes, Darren"},{"first_name":"Paul","full_name":"O’Neill, Paul","last_name":"O’Neill"},{"last_name":"Moore","first_name":"Karen","full_name":"Moore, Karen"},{"first_name":"Nela","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","last_name":"Nikolic","full_name":"Nikolic, Nela","orcid":"0000-0001-9068-6090"},{"last_name":"Petrov","first_name":"Peter","full_name":"Petrov, Peter"},{"full_name":"Milner, David S.","first_name":"David S.","last_name":"Milner"},{"last_name":"Roy","full_name":"Roy, Sumita","first_name":"Sumita"},{"first_name":"Kate","last_name":"Heesom","full_name":"Heesom, Kate"},{"first_name":"Thomas A.","last_name":"Richards","full_name":"Richards, Thomas A."},{"full_name":"Tsaneva-Atanasova, Krasimira","first_name":"Krasimira","last_name":"Tsaneva-Atanasova"},{"first_name":"Stefano","last_name":"Pagliara","full_name":"Pagliara, Stefano"}],"publication":"Communications Biology","oa_version":"Published Version","acknowledgement":"G.G. was supported by an EPSRC DTP PhD studentship (EP/M506527/1). M.V. and K.T.A. gratefully acknowledge financial support from the EPSRC (EP/N014391/1). U.L. was supported through a BBSRC grant (BB/V008021/1) and an MRC Proximity to Discovery EXCITEME2 grant (MCPC17189). This work was further supported by a Royal Society Research Grant (RG180007) awarded to S.P. and a QUEX Initiator grant awarded to S.P. and K.T.A.. D.S.M., T.A.R. and S.P.’s work in this area is also supported by a Marie Skłodowska-Curie project SINGEK (H2020-MSCA-ITN-2015-675752) and the Gordon and Betty Moore Foundation Marine Microbiology Initiative (GBMF5514). B.M.I. acknowledges support from a Wellcome Trust Institutional Strategic Support Award to the University of Exeter (204909/Z/16/Z). This project utilised equipment funded by the Wellcome Trust Institutional Strategic Support Fund (WT097835MF), Wellcome Trust Multi User Equipment Award (WT101650MA) and BBSRC LOLA award (BB/K003240/1).","_id":"11339","title":"Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells","publication_identifier":{"eissn":["2399-3642"]},"file_date_updated":"2022-05-02T06:26:26Z","date_published":"2022-04-20T00:00:00Z","date_created":"2022-05-01T22:01:41Z","volume":5,"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)"},"type":"journal_article","article_processing_charge":"No","month":"04","language":[{"iso":"eng"}],"has_accepted_license":"1","department":[{"_id":"CaGu"}],"status":"public","date_updated":"2023-08-03T06:45:26Z","day":"20","abstract":[{"text":"The interaction between a cell and its environment shapes fundamental intracellular processes such as cellular metabolism. In most cases growth rate is treated as a proximal metric for understanding the cellular metabolic status. However, changes in growth rate might not reflect metabolic variations in individuals responding to environmental fluctuations. Here we use single-cell microfluidics-microscopy combined with transcriptomics, proteomics and mathematical modelling to quantify the accumulation of glucose within Escherichia coli cells. In contrast to the current consensus, we reveal that environmental conditions which are comparatively unfavourable for growth, where both nutrients and salinity are depleted, increase glucose accumulation rates in individual bacteria and population subsets. We find that these changes in metabolic function are underpinned by variations at the translational and posttranslational level but not at the transcriptional level and are not dictated by changes in cell size. The metabolic response-characteristics identified greatly advance our fundamental understanding of the interactions between bacteria and their environment and have important ramifications when investigating cellular processes where salinity plays an important role.","lang":"eng"}],"fulldoi":"https://doi.org/10.1038/s42003-022-03336-6"},{"article_processing_charge":"No","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)"},"type":"journal_article","volume":15,"date_created":"2022-08-01T09:04:27Z","day":"13","date_updated":"2025-04-14T09:24:53Z","fulldoi":"https://doi.org/10.1186/s13104-022-06061-9","abstract":[{"lang":"eng","text":"Objective: MazF is a sequence-specific endoribonuclease-toxin of the MazEF toxin–antitoxin system. MazF cleaves single-stranded ribonucleic acid (RNA) regions at adenine–cytosine–adenine (ACA) sequences in the bacterium Escherichia coli. The MazEF system has been used in various biotechnology and synthetic biology applications. In this study, we infer how ectopic mazF overexpression affects production of heterologous proteins. To this end, we quantified the levels of fluorescent proteins expressed in E. coli from reporters translated from the ACA-containing or ACA-less messenger RNAs (mRNAs). Additionally, we addressed the impact of the 5′-untranslated region of these reporter mRNAs under the same conditions by comparing expression from mRNAs that comprise (canonical mRNA) or lack this region (leaderless mRNA).\r\nResults: Flow cytometry analysis indicates that during mazF overexpression, fluorescent proteins are translated from the canonical as well as leaderless mRNAs. Our analysis further indicates that longer mazF overexpression generally increases the concentration of fluorescent proteins translated from ACA-less mRNAs, however it also substantially increases bacterial population heterogeneity. Finally, our results suggest that the strength and duration of mazF overexpression should be optimized for each experimental setup, to maximize the heterologous protein production and minimize the amount of phenotypic heterogeneity in bacterial populations, which is unfavorable in biotechnological processes."}],"has_accepted_license":"1","language":[{"iso":"eng"}],"month":"05","department":[{"_id":"CaGu"}],"status":"public","oa_version":"Published Version","_id":"11713","acknowledgement":"We acknowledge the Max Perutz Labs FACS Facility together with Thomas Sauer. NN is grateful to Călin C. Guet for his support.\r\nThis work was funded by the Elise Richter grant V738 of the Austrian Science Fund (FWF), and the FWF Lise Meitner grant M1697, to NN; and by the FWF grant P22249, FWF Special Research Program RNA-REG F43 (subproject F4316), and FWF doctoral program RNA Biology (W1207), to IM. Open access funding provided by the Austrian Science Fund.","publication":"BMC Research Notes","scopus_import":"1","author":[{"orcid":"0000-0001-9068-6090","first_name":"Nela","full_name":"Nikolic, Nela","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","last_name":"Nikolic"},{"full_name":"Sauert, Martina","first_name":"Martina","last_name":"Sauert"},{"full_name":"Albanese, Tanino G.","first_name":"Tanino G.","last_name":"Albanese"},{"first_name":"Isabella","full_name":"Moll, Isabella","last_name":"Moll"}],"external_id":{"pmid":["35562780"]},"date_published":"2022-05-13T00:00:00Z","file_date_updated":"2022-08-01T09:24:42Z","publication_identifier":{"issn":["1756-0500"]},"title":"Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli","quality_controlled":"1","ddc":["570"],"year":"2022","doi":"10.1186/s13104-022-06061-9","corr_author":"1","citation":{"ama":"Nikolic N, Sauert M, Albanese TG, Moll I. Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli. <i>BMC Research Notes</i>. 2022;15. doi:<a href=\"https://doi.org/10.1186/s13104-022-06061-9\">10.1186/s13104-022-06061-9</a>","short":"N. Nikolic, M. Sauert, T.G. Albanese, I. Moll, BMC Research Notes 15 (2022).","mla":"Nikolic, Nela, et al. “Quantifying Heterologous Gene Expression during Ectopic MazF Production in Escherichia Coli.” <i>BMC Research Notes</i>, vol. 15, 173, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1186/s13104-022-06061-9\">10.1186/s13104-022-06061-9</a>.","chicago":"Nikolic, Nela, Martina Sauert, Tanino G. Albanese, and Isabella Moll. “Quantifying Heterologous Gene Expression during Ectopic MazF Production in Escherichia Coli.” <i>BMC Research Notes</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1186/s13104-022-06061-9\">https://doi.org/10.1186/s13104-022-06061-9</a>.","apa":"Nikolic, N., Sauert, M., Albanese, T. G., &#38; Moll, I. (2022). Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli. <i>BMC Research Notes</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s13104-022-06061-9\">https://doi.org/10.1186/s13104-022-06061-9</a>","ieee":"N. Nikolic, M. Sauert, T. G. Albanese, and I. Moll, “Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli,” <i>BMC Research Notes</i>, vol. 15. Springer Nature, 2022.","ista":"Nikolic N, Sauert M, Albanese TG, Moll I. 2022. Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli. BMC Research Notes. 15, 173."},"publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1186/s13104-022-06152-7"}]},"project":[{"call_identifier":"FWF","name":"Bacterial toxin-antitoxin systems as antiphage defense mechanisms","grant_number":"V00738","_id":"26956E74-B435-11E9-9278-68D0E5697425"}],"article_number":"173","article_type":"letter_note","pmid":1,"file":[{"file_name":"2022_BMCResearchNotes_Nikolic.pdf","date_updated":"2022-08-01T09:24:42Z","checksum":"008156e5340e9789f0f6d82bde4d347a","file_id":"11714","success":1,"creator":"dernst","access_level":"open_access","content_type":"application/pdf","file_size":1545310,"relation":"main_file","date_created":"2022-08-01T09:24:42Z"}],"keyword":["General Biochemistry","Genetics and Molecular Biology","General Medicine"],"publisher":"Springer Nature","intvolume":"        15"},{"publisher":"eLife Sciences Publications","intvolume":"        11","file":[{"date_updated":"2023-01-23T08:56:21Z","file_name":"2022_eLife_Tomanek.pdf","access_level":"open_access","creator":"dernst","success":1,"file_id":"12338","checksum":"9321fd5f06ff59d5e2d33daee84b3da1","relation":"main_file","file_size":8835954,"content_type":"application/pdf","date_created":"2023-01-23T08:56:21Z"}],"pmid":1,"article_number":"e82240","article_type":"original","isi":1,"related_material":{"record":[{"status":"public","id":"12339","relation":"research_data"}],"link":[{"url":"https://doi.org/10.5281/zenodo.6974122","relation":"software"}]},"oa":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ieee":"I. Tomanek and C. C. Guet, “Adaptation dynamics between copynumber and point mutations,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","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>","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>.","chicago":"Tomanek, Isabella, and Calin C Guet. “Adaptation Dynamics between Copynumber and Point Mutations.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/ELIFE.82240\">https://doi.org/10.7554/ELIFE.82240</a>.","short":"I. Tomanek, C.C. Guet, ELife 11 (2022).","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>"},"publication_status":"published","corr_author":"1","doi":"10.7554/ELIFE.82240","year":"2022","quality_controlled":"1","ddc":["570"],"publication_identifier":{"eissn":["2050-084X"]},"title":"Adaptation dynamics between copynumber and point mutations","date_published":"2022-12-22T00:00:00Z","file_date_updated":"2023-01-23T08:56:21Z","author":[{"last_name":"Tomanek","id":"3981F020-F248-11E8-B48F-1D18A9856A87","full_name":"Tomanek, Isabella","first_name":"Isabella","orcid":"0000-0001-6197-363X"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C"}],"scopus_import":"1","publication":"eLife","external_id":{"isi":["000912674700001"],"pmid":["36546673"]},"_id":"12333","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.","oa_version":"Published Version","department":[{"_id":"CaGu"}],"status":"public","has_accepted_license":"1","month":"12","language":[{"iso":"eng"}],"fulldoi":"https://doi.org/10.7554/ELIFE.82240","abstract":[{"lang":"eng","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."}],"day":"22","date_updated":"2025-03-06T14:03:50Z","date_created":"2023-01-22T23:00:55Z","volume":11,"article_processing_charge":"No","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)"},"type":"journal_article"},{"author":[{"orcid":"0000-0001-6197-363X","id":"3981F020-F248-11E8-B48F-1D18A9856A87","first_name":"Isabella","full_name":"Tomanek, Isabella","last_name":"Tomanek"},{"full_name":"Guet, Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","orcid":"0000-0001-6220-2052"}],"_id":"12339","oa_version":"Published Version","main_file_link":[{"url":"https://doi.org/10.5061/dryad.rfj6q57ds","open_access":"1"}],"related_material":{"record":[{"id":"12333","relation":"used_in_publication","status":"public"}]},"oa":1,"title":"Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose","publisher":"Dryad","date_published":"2022-12-23T00:00:00Z","year":"2022","doi":"10.5061/dryad.rfj6q57ds","date_created":"2023-01-23T09:00:37Z","article_processing_charge":"No","type":"research_data_reference","ddc":["570"],"status":"public","department":[{"_id":"CaGu"}],"month":"12","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","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."}],"fulldoi":"https://doi.org/10.5061/dryad.rfj6q57ds","citation":{"ama":"Tomanek I, Guet CC. Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose. 2022. doi:<a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">10.5061/dryad.rfj6q57ds</a>","short":"I. Tomanek, C.C. Guet, (2022).","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>.","ieee":"I. Tomanek and C. C. Guet, “Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose.” Dryad, 2022.","apa":"Tomanek, I., &#38; Guet, C. C. (2022). Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose. Dryad. <a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">https://doi.org/10.5061/dryad.rfj6q57ds</a>","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>.","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>."},"corr_author":"1","day":"23","date_updated":"2025-03-06T14:03:50Z"},{"publication_status":"published","citation":{"short":"M. Lagator, S. Sarikas, M. Steinrück, D. Toledo-Aparicio, J.P. Bollback, C.C. Guet, G. Tkačik, ELife 11 (2022).","ama":"Lagator M, Sarikas S, Steinrück M, et al. Predicting bacterial promoter function and evolution from random sequences. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.64543\">10.7554/eLife.64543</a>","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.","apa":"Lagator, M., Sarikas, S., Steinrück, M., Toledo-Aparicio, D., Bollback, J. P., Guet, C. C., &#38; Tkačik, G. (2022). Predicting bacterial promoter function and evolution from random sequences. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.64543\">https://doi.org/10.7554/eLife.64543</a>","ista":"Lagator M, Sarikas S, Steinrück M, Toledo-Aparicio D, Bollback JP, Guet CC, Tkačik G. 2022. Predicting bacterial promoter function and evolution from random sequences. eLife. 11, e64543.","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>.","chicago":"Lagator, Mato, Srdjan Sarikas, Magdalena Steinrück, David Toledo-Aparicio, Jonathan P Bollback, Calin C Guet, and Gašper Tkačik. “Predicting Bacterial Promoter Function and Evolution from Random Sequences.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.64543\">https://doi.org/10.7554/eLife.64543</a>."},"corr_author":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["576"],"quality_controlled":"1","year":"2022","doi":"10.7554/eLife.64543","ec_funded":1,"file":[{"file_name":"2022_ELife_Lagator.pdf","date_updated":"2022-02-07T07:14:09Z","file_id":"10739","checksum":"decdcdf600ff51e9a9703b49ca114170","access_level":"open_access","creator":"cchlebak","success":1,"content_type":"application/pdf","file_size":5604343,"relation":"main_file","date_created":"2022-02-07T07:14:09Z"}],"intvolume":"        11","publisher":"eLife Sciences Publications","isi":1,"project":[{"call_identifier":"H2020","name":"Selective Barriers to Horizontal Gene Transfer","grant_number":"648440","_id":"2578D616-B435-11E9-9278-68D0E5697425"}],"oa":1,"pmid":1,"article_type":"original","article_number":"e64543","abstract":[{"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.","lang":"eng"}],"fulldoi":"https://doi.org/10.7554/eLife.64543","date_updated":"2025-03-31T16:00:23Z","day":"26","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"NiBa"}],"status":"public","month":"01","language":[{"iso":"eng"}],"has_accepted_license":"1","article_processing_charge":"No","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)"},"type":"journal_article","date_created":"2022-02-06T23:01:32Z","volume":11,"file_date_updated":"2022-02-07T07:14:09Z","date_published":"2022-01-26T00:00:00Z","title":"Predicting bacterial promoter function and evolution from random sequences","publication_identifier":{"eissn":["2050-084X"]},"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.","_id":"10736","oa_version":"Published Version","external_id":{"pmid":["35080492"],"isi":["000751104400001"]},"author":[{"first_name":"Mato","full_name":"Lagator, Mato","last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Srdjan","id":"35F0286E-F248-11E8-B48F-1D18A9856A87","full_name":"Sarikas, Srdjan","last_name":"Sarikas"},{"orcid":"0000-0003-1229-9719","last_name":"Steinrück","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","first_name":"Magdalena","full_name":"Steinrück, Magdalena"},{"full_name":"Toledo-Aparicio, David","first_name":"David","last_name":"Toledo-Aparicio"},{"orcid":"0000-0002-4624-4612","first_name":"Jonathan P","last_name":"Bollback","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","full_name":"Bollback, Jonathan P"},{"orcid":"0000-0001-6220-2052","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","first_name":"Calin C"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik","full_name":"Tkačik, Gašper","first_name":"Gašper","orcid":"0000-0002-6699-1455"}],"scopus_import":"1","publication":"eLife"}]