[{"quality_controlled":"1","intvolume":"        17","date_updated":"2026-06-02T07:14:35Z","OA_place":"publisher","file":[{"date_created":"2026-06-02T07:11:12Z","access_level":"open_access","file_id":"21936","file_name":"2026_NatureComm_Buchholz.pdf","checksum":"aa29f8806908dc0469dff21e2d5ad01f","date_updated":"2026-06-02T07:11:12Z","success":1,"relation":"main_file","creator":"dernst","content_type":"application/pdf","file_size":1276166}],"author":[{"last_name":"Buchholz","first_name":"Florian","full_name":"Buchholz, Florian"},{"full_name":"Upterworth, Lina M.","first_name":"Lina M.","last_name":"Upterworth"},{"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","first_name":"Kira","last_name":"Haas"},{"last_name":"Schütz","first_name":"Daniel","full_name":"Schütz, Daniel"},{"last_name":"Savietto Scholz","first_name":"Abigail","full_name":"Savietto Scholz, Abigail"},{"first_name":"Aditi","full_name":"Batra, Aditi","last_name":"Batra"},{"last_name":"Pal","full_name":"Pal, Surajit","first_name":"Surajit"},{"full_name":"Banerjee, Samarpita","first_name":"Samarpita","last_name":"Banerjee"},{"last_name":"Dubey","first_name":"Badri N.","full_name":"Dubey, Badri N."},{"last_name":"Franzenburg","full_name":"Franzenburg, Sören","first_name":"Sören"},{"first_name":"Barbara","full_name":"Kalsdorf, Barbara","last_name":"Kalsdorf"},{"first_name":"Klaus F.","full_name":"Rabe, Klaus F.","last_name":"Rabe"},{"last_name":"Nurjadi","first_name":"Dennis","full_name":"Nurjadi, Dennis"},{"last_name":"Rupp","first_name":"Jan","full_name":"Rupp, Jan"},{"full_name":"Andersson, Dan I.","first_name":"Dan I.","last_name":"Andersson"},{"last_name":"Sondermann","full_name":"Sondermann, Holger","first_name":"Holger"},{"last_name":"Bramkamp","first_name":"Marc","full_name":"Bramkamp, Marc"},{"orcid":"0000-0001-9480-5261","last_name":"Römhild","full_name":"Römhild, Roderich","first_name":"Roderich","id":"68E56E44-62B0-11EA-B963-444F3DDC885E"},{"full_name":"Schulenburg, Hinrich","first_name":"Hinrich","last_name":"Schulenburg"}],"oa":1,"status":"public","publication":"Nature Communications","language":[{"iso":"eng"}],"publisher":"Springer Nature","date_created":"2026-05-31T22:02:12Z","PlanS_conform":"1","article_type":"original","oa_version":"Published Version","has_accepted_license":"1","volume":17,"OA_type":"gold","article_processing_charge":"Yes (via OA deal)","citation":{"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>.","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.","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>","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>","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.","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>.","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)."},"ddc":["570"],"day":"20","publication_status":"published","date_published":"2026-05-20T00:00:00Z","project":[{"_id":"bd6f94d1-d553-11ed-ba76-ae9f07250f74","name":"Non-canonical antibiotic interactions","grant_number":"E219"}],"corr_author":"1","_id":"21928","department":[{"_id":"CaGu"}],"file_date_updated":"2026-06-02T07:11:12Z","scopus_import":"1","publication_identifier":{"eissn":["2041-1723"]},"doi":"10.1038/s41467-026-71178-5","article_number":"4487","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","abstract":[{"lang":"eng","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."}],"DOAJ_listed":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Robust antibiotic sensitization of pathogenic Pseudomonas aeruginosa via negative hysteresis in the cell envelope","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"year":"2026","month":"05","type":"journal_article"},{"date_created":"2026-06-10T07:37:12Z","publisher":"Elsevier","publication":"Current Opinion in Genetics & Development","language":[{"iso":"eng"}],"oa_version":"Published Version","arxiv":1,"PlanS_conform":"1","article_type":"original","date_updated":"2026-06-16T12:37:02Z","OA_place":"publisher","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.gde.2026.102483"}],"intvolume":"        99","quality_controlled":"1","status":"public","oa":1,"author":[{"orcid":"0000-0003-2977-7844","last_name":"Mascolo","first_name":"Elia","full_name":"Mascolo, Elia","id":"776a6ed0-a053-11f0-8635-80b95e0e0d53"},{"first_name":"Reka E","full_name":"Körei, Reka E","id":"50FDE43E-AA30-11E9-A72B-8A12E6697425","last_name":"Körei"},{"last_name":"Herrera-Álvarez","full_name":"Herrera-Álvarez, Santiago","first_name":"Santiago"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","full_name":"Guet, Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052"},{"last_name":"Crocker","full_name":"Crocker, Justin","first_name":"Justin"},{"last_name":"Tkačik","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"Yes (via OA deal)","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>","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>","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>."},"ddc":["570"],"day":"09","publication_status":"published","volume":99,"OA_type":"hybrid","corr_author":"1","date_published":"2026-05-09T00:00:00Z","has_accepted_license":"1","doi":"10.1016/j.gde.2026.102483","publication_identifier":{"issn":["0959-437X"],"eissn":["1879-0380"]},"scopus_import":"1","department":[{"_id":"GradSch"},{"_id":"CaGu"},{"_id":"GaTk"}],"_id":"21983","external_id":{"arxiv":["2601.19681"]},"year":"2026","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"month":"05","type":"journal_article","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.).","article_number":"102483","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps","abstract":[{"lang":"eng","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."}]},{"file_date_updated":"2026-06-16T12:45:09Z","publication_identifier":{"issn":["0014-3820"],"eissn":["1558-5646"]},"doi":"10.1093/evolut/qpag061","issue":"6","scopus_import":"1","department":[{"_id":"CaGu"}],"_id":"21985","year":"2026","external_id":{"pmid":["41968110"]},"tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","month":"06","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.","title":"Responsive lysogeny under nonproductive phage binding","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"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."}],"publisher":"Oxford University Press","date_created":"2026-06-10T07:38:12Z","language":[{"iso":"eng"}],"publication":"Evolution","page":"1365-1373","related_material":{"link":[{"url":"https://github.com/theguetlab/responsive-lysogeny","relation":"software"}]},"oa_version":"Published Version","article_type":"original","PlanS_conform":"1","OA_place":"publisher","date_updated":"2026-06-16T12:46:02Z","intvolume":"        80","quality_controlled":"1","status":"public","author":[{"last_name":"Wu","full_name":"Wu, Bryan","first_name":"Bryan","id":"3C521EBA-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-6220-2052","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","full_name":"Guet, Calin C"}],"oa":1,"file":[{"access_level":"open_access","date_created":"2026-06-16T12:45:09Z","file_name":"2026_Evolution_Wu.pdf","checksum":"6d0f48566a7a36cb0c469e1968c9cb1c","file_id":"22015","relation":"main_file","creator":"dernst","date_updated":"2026-06-16T12:45:09Z","success":1,"content_type":"application/pdf","file_size":2077781}],"publication_status":"published","ddc":["570"],"day":"01","article_processing_charge":"Yes (via OA deal)","citation":{"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>.","short":"B. Wu, C.C. Guet, Evolution 80 (2026) 1365–1373.","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>.","ista":"Wu B, Guet CC. 2026. Responsive lysogeny under nonproductive phage binding. Evolution. 80(6), 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>"},"OA_type":"hybrid","volume":80,"corr_author":"1","date_published":"2026-06-01T00:00:00Z","has_accepted_license":"1"},{"month":"03","type":"research_data","date_published":"2025-03-04T00:00:00Z","corr_author":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"OA_type":"gold","article_processing_charge":"No","citation":{"chicago":"Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper Tkačik, and Calin C Guet. “Data for ‘Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.’” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT:ISTA:19294\">https://doi.org/10.15479/AT:ISTA:19294</a>.","ieee":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet, “Data for ‘Pulsatile basal gene expression as a fitness determinant in bacteria.’” Institute of Science and Technology Austria, 2025.","apa":"Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., &#38; Guet, C. C. (2025). Data for “Pulsatile basal gene expression as a fitness determinant in bacteria.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:19294\">https://doi.org/10.15479/AT:ISTA:19294</a>","short":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, (2025).","ama":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Data for “Pulsatile basal gene expression as a fitness determinant in bacteria.” 2025. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:19294\">10.15479/AT:ISTA:19294</a>","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>.","mla":"Jain, Kirti, et al. <i>Data for “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.”</i> Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:19294\">10.15479/AT:ISTA:19294</a>."},"day":"04","ddc":["570"],"year":"2025","abstract":[{"text":"Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of non-functional “promoter leakiness”, merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the non-canonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g. control of costly-to-induce multi-drug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multi-drug resistance is crucial for effective public health measures.","lang":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Data for \"Pulsatile basal gene expression as a fitness determinant in bacteria\"","has_accepted_license":"1","related_material":{"record":[{"status":"public","id":"19626","relation":"used_in_publication"}]},"oa_version":"Published Version","doi":"10.15479/AT:ISTA:19294","date_created":"2025-03-04T13:27:21Z","publisher":"Institute of Science and Technology Austria","file_date_updated":"2025-03-05T07:39:38Z","file":[{"date_updated":"2025-03-04T13:08:52Z","success":1,"creator":"dernst","relation":"main_file","file_size":269054,"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","date_created":"2025-03-04T13:08:52Z","access_level":"open_access","file_id":"19295","file_name":"Data1.xlsx","checksum":"11a5bab307a4e1e1598a1577d8a2fbb5"},{"date_created":"2025-03-04T13:08:52Z","access_level":"open_access","file_id":"19296","checksum":"3b057894322639f0c1e11fb2e84173e6","file_name":"Data2.xlsx","success":1,"date_updated":"2025-03-04T13:08:52Z","creator":"dernst","relation":"main_file","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","file_size":87143},{"file_size":129101,"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","relation":"main_file","creator":"dernst","date_updated":"2025-03-04T13:08:52Z","success":1,"checksum":"a551e1b79a138bb97ab96979aa475b3c","file_name":"Data3.xlsx","file_id":"19297","access_level":"open_access","date_created":"2025-03-04T13:08:52Z"},{"creator":"dernst","relation":"main_file","date_updated":"2025-03-04T13:08:52Z","success":1,"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","file_size":86243,"access_level":"open_access","date_created":"2025-03-04T13:08:52Z","checksum":"d6909c9bf111f859058082b1a2f970c4","file_name":"Data4.xlsx","file_id":"19298"},{"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","file_size":26049,"success":1,"date_updated":"2025-03-04T13:08:52Z","relation":"main_file","creator":"dernst","file_id":"19299","file_name":"Data5.xlsx","checksum":"e5725a3a118a3f06846104906c8792c7","date_created":"2025-03-04T13:08:52Z","access_level":"open_access"},{"creator":"dernst","relation":"main_file","success":1,"date_updated":"2025-03-04T13:08:52Z","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","file_size":7327253,"access_level":"open_access","date_created":"2025-03-04T13:08:52Z","checksum":"16763c127049f14bd587dc885677dce1","file_name":"RawData_2_3.xlsx","file_id":"19300"},{"file_id":"19301","checksum":"2f3e1a368b4e3abc46bf37e02724f0f4","file_name":"Readme.txt","date_created":"2025-03-05T07:39:38Z","access_level":"open_access","file_size":606,"content_type":"text/plain","date_updated":"2025-03-05T07:39:38Z","success":1,"relation":"main_file","creator":"dernst"}],"oa":1,"author":[{"first_name":"Kirti","full_name":"Jain, Kirti","id":"330F0278-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3809-0449","last_name":"Jain"},{"orcid":"0000-0001-9843-3522","last_name":"Hauschild","full_name":"Hauschild, Robert","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bochkareva, Olga","first_name":"Olga","id":"C4558D3C-6102-11E9-A62E-F418E6697425","orcid":"0000-0003-1006-6639","last_name":"Bochkareva"},{"id":"68E56E44-62B0-11EA-B963-444F3DDC885E","full_name":"Römhild, Roderich","first_name":"Roderich","last_name":"Römhild","orcid":"0000-0001-9480-5261"},{"last_name":"Tkačik","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","first_name":"Gašper"},{"first_name":"Calin C","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","orcid":"0000-0001-6220-2052"}],"status":"public","_id":"19294","date_updated":"2026-05-20T08:33:07Z","OA_place":"repository","department":[{"_id":"CaGu"},{"_id":"Bio"},{"_id":"FyKo"},{"_id":"GaTk"}]},{"has_accepted_license":"1","volume":122,"OA_type":"hybrid","article_processing_charge":"Yes (in subscription journal)","citation":{"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>.","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.","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>","short":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, Proceedings of the National Academy of Sciences 122 (2025).","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>","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>."},"day":"15","ddc":["570"],"publication_status":"published","project":[{"_id":"c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473","name":"Tools for automation and feedback microscopy","grant_number":"CZI01"},{"grant_number":"E219","_id":"bd6f94d1-d553-11ed-ba76-ae9f07250f74","name":"Non-canonical antibiotic interactions"},{"grant_number":"I05127","name":"Evolutionary analysis of gene regulation","_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181"}],"date_published":"2025-04-15T00:00:00Z","corr_author":"1","quality_controlled":"1","intvolume":"       122","date_updated":"2026-05-20T08:33:08Z","OA_place":"publisher","APC_amount":"5949 EUR","isi":1,"file":[{"creator":"dernst","relation":"main_file","date_updated":"2025-06-24T07:27:43Z","success":1,"content_type":"application/pdf","file_size":2949523,"access_level":"open_access","date_created":"2025-06-24T07:27:43Z","checksum":"115a687f40009660eb4b38b4f6559d41","file_name":"2025_PNAS_Jain.pdf","file_id":"19888"}],"author":[{"id":"330F0278-F248-11E8-B48F-1D18A9856A87","full_name":"Jain, Kirti","first_name":"Kirti","last_name":"Jain","orcid":"0000-0002-3809-0449"},{"last_name":"Hauschild","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"id":"C4558D3C-6102-11E9-A62E-F418E6697425","first_name":"Olga","full_name":"Bochkareva, Olga","orcid":"0000-0003-1006-6639","last_name":"Bochkareva"},{"orcid":"0000-0001-9480-5261","last_name":"Römhild","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","first_name":"Roderich","full_name":"Römhild, Roderich"},{"orcid":"0000-0002-6699-1455","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","first_name":"Gašper"},{"last_name":"Guet","orcid":"0000-0001-6220-2052","first_name":"Calin C","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"oa":1,"status":"public","publication":"Proceedings of the National Academy of Sciences","language":[{"iso":"eng"}],"date_created":"2025-04-27T22:02:13Z","publisher":"National Academy of Sciences","article_type":"original","oa_version":"Published Version","related_material":{"record":[{"status":"public","id":"19294","relation":"research_data"}],"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/clockwork-just-for-antibiotic-resistance/","description":"News on ISTA website"}]},"article_number":"e2413709122","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.","abstract":[{"text":"Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of nonfunctional “promoter leakiness,” merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the noncanonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g., control of costly-to-induce multidrug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multidrug resistance is crucial for effective public health measures.","lang":"eng"}],"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Pulsatile basal gene expression as a fitness determinant in bacteria","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"external_id":{"pmid":["40193613"],"isi":["001471235200001"]},"year":"2025","month":"04","type":"journal_article","acknowledged_ssus":[{"_id":"Bio"}],"_id":"19626","department":[{"_id":"CaGu"},{"_id":"Bio"},{"_id":"FyKo"},{"_id":"GaTk"}],"file_date_updated":"2025-06-24T07:27:43Z","scopus_import":"1","doi":"10.1073/pnas.2413709122","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"issue":"15"},{"publication_status":"published","day":"01","ddc":["570"],"article_processing_charge":"Yes (in subscription journal)","citation":{"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.","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>","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>.","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>.","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>","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.","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)."},"OA_type":"hybrid","volume":437,"date_published":"2025-09-01T00:00:00Z","project":[{"call_identifier":"FWF","grant_number":"W1232-B24","_id":"255A6082-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets"}],"has_accepted_license":"1","date_created":"2025-05-25T22:16:39Z","publisher":"Elsevier","language":[{"iso":"eng"}],"publication":"Journal of Molecular Biology","oa_version":"Published Version","article_type":"original","PlanS_conform":"1","OA_place":"publisher","date_updated":"2025-12-30T08:18:25Z","intvolume":"       437","quality_controlled":"1","status":"public","oa":1,"author":[{"last_name":"Antoney","full_name":"Antoney, James","first_name":"James"},{"full_name":"Kainrath, Stephanie","first_name":"Stephanie","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6709-2195","last_name":"Kainrath"},{"last_name":"Dubowsky","full_name":"Dubowsky, Joshua G.","first_name":"Joshua G."},{"first_name":"F. Hafna","full_name":"Ahmed, F. Hafna","last_name":"Ahmed"},{"last_name":"Kang","full_name":"Kang, Suk Woo","first_name":"Suk Woo"},{"last_name":"Mackie","first_name":"Emily R.R.","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"},{"last_name":"Janovjak","orcid":"0000-0002-8023-9315","first_name":"Harald L","full_name":"Janovjak, Harald L","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87"}],"isi":1,"file":[{"file_name":"2025_JourMolecularBiology_Antoney.pdf","checksum":"fb6e84ba7dc92faee97647fd2bc8cca8","file_id":"20892","access_level":"open_access","date_created":"2025-12-30T08:18:07Z","file_size":1682721,"content_type":"application/pdf","creator":"dernst","relation":"main_file","success":1,"date_updated":"2025-12-30T08:18:07Z"}],"year":"2025","external_id":{"isi":["001494762800001"],"pmid":["40324743"]},"tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","month":"09","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.","article_number":"169184","title":"A F420-dependent single domain chemogenetic tool for protein de-dimerization","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"abstract":[{"lang":"eng","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."}],"file_date_updated":"2025-12-30T08:18:07Z","doi":"10.1016/j.jmb.2025.169184","issue":"17","publication_identifier":{"eissn":["1089-8638"],"issn":["0022-2836"]},"scopus_import":"1","department":[{"_id":"CaGu"}],"_id":"19725"},{"corr_author":"1","project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734"},{"grant_number":"V00738","call_identifier":"FWF","name":"Bacterial toxin-antitoxin systems as antiphage defense mechanisms","_id":"26956E74-B435-11E9-9278-68D0E5697425"}],"date_published":"2025-06-11T00:00:00Z","citation":{"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>.","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.","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>","short":"N. Nikolic, M. Pleska, T. Bergmiller, C.C. Guet, Biology Letters 21 (2025).","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>","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>."},"article_processing_charge":"Yes (via OA deal)","publication_status":"published","day":"11","ddc":["570"],"volume":21,"OA_type":"hybrid","has_accepted_license":"1","oa_version":"Published Version","article_type":"original","publisher":"The Royal Society","date_created":"2025-06-22T22:02:06Z","publication":"Biology Letters","language":[{"iso":"eng"}],"status":"public","isi":1,"file":[{"access_level":"open_access","date_created":"2025-06-23T11:34:39Z","file_name":"2025_BiologyLetters_Nikolic.pdf","checksum":"016f644ed068f8609ded306ad26dbd3f","file_id":"19873","creator":"dernst","relation":"main_file","date_updated":"2025-06-23T11:34:39Z","success":1,"file_size":1850797,"content_type":"application/pdf"}],"oa":1,"author":[{"last_name":"Nikolic","orcid":"0000-0001-9068-6090","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","full_name":"Nikolic, Nela","first_name":"Nela"},{"orcid":"0000-0001-7460-7479","last_name":"Pleska","id":"4569785E-F248-11E8-B48F-1D18A9856A87","first_name":"Maros","full_name":"Pleska, Maros"},{"last_name":"Bergmiller","orcid":"0000-0001-5396-4346","first_name":"Tobias","full_name":"Bergmiller, Tobias","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"}],"date_updated":"2025-09-30T13:38:08Z","OA_place":"publisher","intvolume":"        21","quality_controlled":"1","month":"06","type":"journal_article","external_id":{"isi":["001505019800001"],"pmid":["40494395"]},"year":"2025","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","title":"A bacterial toxin-antitoxin system as a native defence element against RNA phages","abstract":[{"lang":"eng","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."}],"pmid":1,"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.","article_number":"20250080","doi":"10.1098/rsbl.2025.0080","publication_identifier":{"issn":["1744-9561"],"eissn":["1744-957X"]},"issue":"6","scopus_import":"1","ec_funded":1,"file_date_updated":"2025-06-23T11:34:39Z","department":[{"_id":"CaGu"}],"acknowledged_ssus":[{"_id":"LifeSc"}],"_id":"19857"},{"status":"public","author":[{"last_name":"Gallemi","orcid":"0000-0003-4675-6893","full_name":"Gallemi, Marçal","first_name":"Marçal","id":"460C6802-F248-11E8-B48F-1D18A9856A87"},{"id":"310A8E3E-F248-11E8-B48F-1D18A9856A87","full_name":"Montesinos López, Juan C","first_name":"Juan C","last_name":"Montesinos López","orcid":"0000-0001-9179-6099"},{"last_name":"Zarevski","full_name":"Zarevski, Nikola","first_name":"Nikola","id":"18e95355-e05a-11ea-a9c0-8fba1b89e83a"},{"last_name":"Pribyl","full_name":"Pribyl, Jan","first_name":"Jan"},{"last_name":"Skládal","full_name":"Skládal, Petr","first_name":"Petr"},{"last_name":"Hannezo","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","first_name":"Edouard B","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Benková","orcid":"0000-0002-8510-9739","full_name":"Benková, Eva","first_name":"Eva","id":"38F4F166-F248-11E8-B48F-1D18A9856A87"}],"oa":1,"APC_amount":"3642,79 EUR","file":[{"date_created":"2025-07-31T07:28:54Z","access_level":"open_access","file_id":"20093","file_name":"2025_FrontiersPlantSc_Gallemi.pdf","checksum":"9e6b8b53ba56d4a24a9bd91cf6d2dc58","date_updated":"2025-07-31T07:28:54Z","success":1,"creator":"dernst","relation":"main_file","file_size":3665187,"content_type":"application/pdf"}],"isi":1,"OA_place":"publisher","date_updated":"2026-05-20T07:53:03Z","intvolume":"        16","quality_controlled":"1","oa_version":"Published Version","article_type":"original","PlanS_conform":"1","publisher":"Frontiers Media","date_created":"2025-07-27T22:01:26Z","language":[{"iso":"eng"}],"publication":"Frontiers in Plant Science","has_accepted_license":"1","corr_author":"1","project":[{"name":"Hormonal cross-talk in plant organogenesis","_id":"253FCA6A-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"207362"},{"_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854","name":"IST Austria Open Access Fund"}],"date_published":"2025-07-04T00:00:00Z","ddc":["580"],"publication_status":"published","day":"04","article_processing_charge":"Yes","citation":{"short":"M. Gallemi, J.C. Montesinos López, N. Zarevski, J. Pribyl, P. Skládal, E.B. Hannezo, E. Benková, Frontiers in Plant Science 16 (2025).","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>","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.","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>.","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>","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."},"OA_type":"gold","volume":16,"department":[{"_id":"EdHa"},{"_id":"EvBe"},{"_id":"CaGu"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"E-Lib"}],"_id":"20080","publication_identifier":{"eissn":["1664-462X"]},"doi":"10.3389/fpls.2025.1612366","scopus_import":"1","file_date_updated":"2025-07-31T07:28:54Z","ec_funded":1,"title":"Dual role of pectin methyl esterase activity in the regulation of plant cell wall biophysical properties","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"DOAJ_listed":"1","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"}],"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.","article_number":"1612366","type":"journal_article","month":"07","year":"2025","external_id":{"pmid":["40688689"],"isi":["001530690900001"]},"tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"}},{"scopus_import":"1","issue":"2","doi":"10.1093/genetics/iyae191","publication_identifier":{"eissn":["1943-2631"]},"file_date_updated":"2025-04-16T09:41:04Z","_id":"18936","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"type":"journal_article","month":"02","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"year":"2025","external_id":{"isi":["001379194200001"],"pmid":["39601269"]},"pmid":1,"abstract":[{"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.","lang":"eng"}],"title":"Linking molecular mechanisms to their evolutionary consequences: a primer","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_number":"iyae191","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.","article_type":"original","oa_version":"Published Version","language":[{"iso":"eng"}],"publication":"Genetics","date_created":"2025-01-29T08:21:35Z","publisher":"Oxford University Press","author":[{"id":"483E70DE-F248-11E8-B48F-1D18A9856A87","first_name":"Rok","full_name":"Grah, Rok","orcid":"0000-0003-2539-3560","last_name":"Grah"},{"last_name":"Guet","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","full_name":"Guet, Calin C"},{"first_name":"Gašper","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","last_name":"Tkačik"},{"last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","full_name":"Lagator, Mato","first_name":"Mato"}],"oa":1,"isi":1,"file":[{"relation":"main_file","creator":"dernst","date_updated":"2025-04-16T09:41:04Z","success":1,"content_type":"application/pdf","file_size":1511688,"access_level":"open_access","date_created":"2025-04-16T09:41:04Z","checksum":"f730e416795969449ef49d97b82ac494","file_name":"2025_Genetics_Grah.pdf","file_id":"19580"}],"status":"public","intvolume":"       229","quality_controlled":"1","OA_place":"publisher","date_updated":"2025-05-19T14:08:02Z","date_published":"2025-02-01T00:00:00Z","corr_author":"1","OA_type":"hybrid","volume":229,"day":"01","ddc":["570"],"publication_status":"published","article_processing_charge":"Yes (in subscription journal)","citation":{"short":"R. Grah, C.C. Guet, G. Tkačik, M. Lagator, Genetics 229 (2025).","mla":"Grah, Rok, et al. “Linking Molecular Mechanisms to Their Evolutionary Consequences: A Primer.” <i>Genetics</i>, vol. 229, no. 2, iyae191, Oxford University Press, 2025, doi:<a href=\"https://doi.org/10.1093/genetics/iyae191\">10.1093/genetics/iyae191</a>.","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>","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>","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.","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>."},"has_accepted_license":"1"},{"alternative_title":["ISTA Thesis"],"year":"2025","month":"10","type":"dissertation","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."}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","title":"An examination on phages as a naturally composable system","supervisor":[{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","first_name":"Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"}],"file_date_updated":"2026-04-30T22:30:02Z","doi":"10.15479/AT-ISTA-20470","publication_identifier":{"issn":["2663-337X"]},"_id":"20470","department":[{"_id":"GradSch"},{"_id":"CaGu"}],"article_processing_charge":"No","citation":{"ieee":"B. Wu, “An examination on phages as a naturally composable system,” Institute of Science and Technology Austria, 2025.","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>","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.","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."},"degree_awarded":"PhD","publication_status":"published","day":"30","ddc":["579"],"date_published":"2025-10-30T00:00:00Z","corr_author":"1","has_accepted_license":"1","language":[{"iso":"eng"}],"publisher":"Institute of Science and Technology Austria","date_created":"2025-10-15T13:30:21Z","oa_version":"Published Version","page":"102","date_updated":"2026-05-06T08:01:28Z","OA_place":"publisher","file":[{"relation":"source_file","creator":"brwu","date_updated":"2026-04-30T22:30:02Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_size":10603235,"embargo_to":"open_access","access_level":"closed","date_created":"2025-10-21T17:33:27Z","checksum":"d32ea83f259f6b0506325cd57b1d44c3","file_name":"2025_Wu_Bryan_Thesis.docx","file_id":"20516"},{"file_size":6251936,"content_type":"application/pdf","date_updated":"2026-04-30T22:30:02Z","relation":"main_file","creator":"brwu","file_id":"20517","file_name":"2025_Wu_Bryan_Thesis.pdf","checksum":"53590046fd3244c5550b4022282449d2","date_created":"2025-10-21T17:33:26Z","embargo":"2026-04-30","access_level":"open_access"}],"oa":1,"author":[{"id":"3C521EBA-F248-11E8-B48F-1D18A9856A87","full_name":"Wu, Bryan","first_name":"Bryan","last_name":"Wu"}],"status":"public"},{"has_accepted_license":"1","volume":53,"citation":{"short":"W.C. Lo, E. Krasnopeeva, T. Pilizota, Annual Review of Biophysics 53 (2024) 487–510.","ista":"Lo WC, Krasnopeeva E, Pilizota T. 2024. Bacterial Electrophysiology. Annual Review of Biophysics. 53, 487–510.","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>","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>.","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>","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>.","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."},"article_processing_charge":"Yes (in subscription journal)","ddc":["570"],"publication_status":"published","day":"01","project":[{"name":"Bacterial cytoplasm glass transition: passive physiological switch or active survival strategy","_id":"eb872896-77a9-11ec-83b8-f59a38ec17f8","grant_number":"ALTF 44-2021"}],"date_published":"2024-07-01T00:00:00Z","quality_controlled":"1","intvolume":"        53","date_updated":"2025-09-08T08:34:43Z","file":[{"success":1,"date_updated":"2024-07-29T10:56:01Z","relation":"main_file","creator":"dernst","file_size":1276645,"content_type":"application/pdf","date_created":"2024-07-29T10:56:01Z","access_level":"open_access","file_id":"17339","checksum":"e0505553b3cee624fa865f0cc5a99ecc","file_name":"2024_AnnualReviewBiophys_Lo.pdf"}],"isi":1,"oa":1,"author":[{"last_name":"Lo","full_name":"Lo, Wei Chang","first_name":"Wei Chang"},{"last_name":"Krasnopeeva","full_name":"Krasnopeeva, Ekaterina","first_name":"Ekaterina","id":"1F1EE44A-BF83-11EA-B3C1-BB9CC619BF3A"},{"full_name":"Pilizota, Teuta","first_name":"Teuta","last_name":"Pilizota"}],"status":"public","publication":"Annual Review of Biophysics","language":[{"iso":"eng"}],"date_created":"2024-07-28T22:01:09Z","publisher":"Annual Reviews","article_type":"original","oa_version":"Published Version","page":"487-510","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.","abstract":[{"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.","lang":"eng"}],"pmid":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","title":"Bacterial Electrophysiology","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"external_id":{"isi":["001278237500021"],"pmid":["38382113"]},"year":"2024","month":"07","type":"journal_article","_id":"17325","department":[{"_id":"CaGu"}],"file_date_updated":"2024-07-29T10:56:01Z","scopus_import":"1","publication_identifier":{"eissn":["1936-1238"],"issn":["1936-122X"]},"doi":"10.1146/annurev-biophys-030822-032215"},{"scopus_import":"1","publication_identifier":{"eissn":["1664-302X"]},"doi":"10.3389/fmicb.2023.1049255","file_date_updated":"2023-07-31T07:16:34Z","_id":"12478","department":[{"_id":"CaGu"}],"type":"journal_article","month":"06","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"year":"2023","external_id":{"isi":["001030002600001"],"pmid":["37485524"]},"pmid":1,"abstract":[{"text":"In Gram negative bacteria, the multiple antibiotic resistance or mar operon, is known to control the expression of multi-drug efflux genes that protect bacteria from a wide range of drugs. As many different chemical compounds can induce this operon, identifying the parameters that govern the dynamics of its induction is crucial to better characterize the processes of tolerance and resistance. Most experiments have assumed that the properties of the mar transcriptional network can be inferred from population measurements. However, measurements from an asynchronous population of cells can mask underlying phenotypic variations of single cells. We monitored the activity of the mar promoter in single Escherichia coli cells in linear micro-colonies and established that the response to a steady level of inducer was most heterogeneous within individual colonies for an intermediate value of inducer. Specifically, sub-lineages defined by contiguous daughter-cells exhibited similar promoter activity, whereas activity was greatly variable between different sub-lineages. Specific sub-trees of uniform promoter activity persisted over several generations. Statistical analyses of the lineages suggest that the presence of these sub-trees is the signature of an inducible memory of the promoter state that is transmitted from mother to daughter cells. This single-cell study reveals that the degree of epigenetic inheritance changes as a function of inducer concentration, suggesting that phenotypic inheritance may be an inducible phenotype.","lang":"eng"}],"title":"Monitoring lineages of growing and dividing bacteria reveals an inducible memory of <i>mar</i> operon expression","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_number":"1049255","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.","article_type":"original","oa_version":"Published Version","language":[{"iso":"eng"}],"publication":"Frontiers in Microbiology","publisher":"Frontiers","date_created":"2023-02-02T08:13:28Z","author":[{"first_name":"Calin C","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","orcid":"0000-0001-6220-2052"},{"first_name":"L","full_name":"Bruneaux, L","last_name":"Bruneaux"},{"last_name":"Oikonomou","first_name":"P","full_name":"Oikonomou, P"},{"last_name":"Aldana","full_name":"Aldana, M","first_name":"M"},{"last_name":"Cluzel","first_name":"P","full_name":"Cluzel, P"}],"oa":1,"file":[{"access_level":"open_access","date_created":"2023-07-31T07:16:34Z","file_name":"2023_FrontiersMicrobiology_Guet.pdf","checksum":"7dd322347512afaa5daf72a0154f2f07","file_id":"13322","creator":"dernst","relation":"main_file","success":1,"date_updated":"2023-07-31T07:16:34Z","content_type":"application/pdf","file_size":6452841}],"isi":1,"status":"public","intvolume":"        14","quality_controlled":"1","date_updated":"2024-10-09T21:03:59Z","date_published":"2023-06-20T00:00:00Z","corr_author":"1","volume":14,"ddc":["570"],"publication_status":"published","day":"20","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>","chicago":"Guet, Calin C, L Bruneaux, P Oikonomou, M Aldana, and P Cluzel. “Monitoring Lineages of Growing and Dividing Bacteria Reveals an Inducible Memory of <i>Mar</i> Operon Expression.” <i>Frontiers in Microbiology</i>. Frontiers, 2023. <a href=\"https://doi.org/10.3389/fmicb.2023.1049255\">https://doi.org/10.3389/fmicb.2023.1049255</a>.","ieee":"C. C. Guet, L. Bruneaux, P. Oikonomou, M. Aldana, and P. Cluzel, “Monitoring lineages of growing and dividing bacteria reveals an inducible memory of <i>mar</i> operon expression,” <i>Frontiers in Microbiology</i>, vol. 14. Frontiers, 2023.","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>","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>."},"article_processing_charge":"Yes","has_accepted_license":"1"},{"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.","article_number":"e64543","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Predicting bacterial promoter function and evolution from random sequences","abstract":[{"lang":"eng","text":"Predicting function from sequence is a central problem of biology. Currently, this is possible only locally in a narrow mutational neighborhood around a wildtype sequence rather than globally from any sequence. Using random mutant libraries, we developed a biophysical model that accounts for multiple features of σ70 binding bacterial promoters to predict constitutive gene expression levels from any sequence. We experimentally and theoretically estimated that 10–20% of random sequences lead to expression and ~80% of non-expressing sequences are one mutation away from a functional promoter. The potential for generating expression from random sequences is so pervasive that selection acts against σ70-RNA polymerase binding sites even within inter-genic, promoter-containing regions. This pervasiveness of σ70-binding sites implies that emergence of promoters is not the limiting step in gene regulatory evolution. Ultimately, the inclusion of novel features of promoter function into a mechanistic model enabled not only more accurate predictions of gene expression levels, but also identified that promoters evolve more rapidly than previously thought."}],"pmid":1,"external_id":{"isi":["000751104400001"],"pmid":["35080492"]},"year":"2022","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"month":"01","type":"journal_article","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"NiBa"}],"_id":"10736","ec_funded":1,"file_date_updated":"2022-02-07T07:14:09Z","publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/eLife.64543","scopus_import":"1","has_accepted_license":"1","article_processing_charge":"No","citation":{"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>","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>.","mla":"Lagator, Mato, et al. “Predicting Bacterial Promoter Function and Evolution from Random Sequences.” <i>ELife</i>, vol. 11, e64543, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.64543\">10.7554/eLife.64543</a>.","ista":"Lagator M, Sarikas S, Steinrück M, Toledo-Aparicio D, Bollback JP, Guet CC, Tkačik G. 2022. Predicting bacterial promoter function and evolution from random sequences. eLife. 11, e64543.","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>","short":"M. Lagator, S. Sarikas, M. Steinrück, D. Toledo-Aparicio, J.P. Bollback, C.C. Guet, G. Tkačik, ELife 11 (2022)."},"day":"26","ddc":["576"],"publication_status":"published","volume":11,"corr_author":"1","date_published":"2022-01-26T00:00:00Z","project":[{"_id":"2578D616-B435-11E9-9278-68D0E5697425","name":"Selective Barriers to Horizontal Gene Transfer","call_identifier":"H2020","grant_number":"648440"}],"date_updated":"2025-03-31T16:00:23Z","intvolume":"        11","quality_controlled":"1","status":"public","file":[{"date_created":"2022-02-07T07:14:09Z","access_level":"open_access","file_id":"10739","file_name":"2022_ELife_Lagator.pdf","checksum":"decdcdf600ff51e9a9703b49ca114170","success":1,"date_updated":"2022-02-07T07:14:09Z","relation":"main_file","creator":"cchlebak","content_type":"application/pdf","file_size":5604343}],"isi":1,"oa":1,"author":[{"last_name":"Lagator","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","full_name":"Lagator, Mato"},{"last_name":"Sarikas","full_name":"Sarikas, Srdjan","first_name":"Srdjan","id":"35F0286E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Steinrück","orcid":"0000-0003-1229-9719","id":"2C023F40-F248-11E8-B48F-1D18A9856A87","full_name":"Steinrück, Magdalena","first_name":"Magdalena"},{"full_name":"Toledo-Aparicio, David","first_name":"David","last_name":"Toledo-Aparicio"},{"full_name":"Bollback, Jonathan P","first_name":"Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","last_name":"Bollback"},{"last_name":"Guet","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","full_name":"Guet, Calin C"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","first_name":"Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455"}],"publisher":"eLife Sciences Publications","date_created":"2022-02-06T23:01:32Z","publication":"eLife","language":[{"iso":"eng"}],"oa_version":"Published Version","article_type":"original"},{"date_created":"2022-03-04T04:33:49Z","publisher":"Springer Nature","publication":"Nature Reviews Microbiology","language":[{"iso":"eng"}],"oa_version":"None","page":"478-490","article_type":"review","date_updated":"2023-08-02T14:41:44Z","intvolume":"        20","quality_controlled":"1","status":"public","isi":1,"author":[{"orcid":"0000-0001-9480-5261","last_name":"Römhild","full_name":"Römhild, Roderich","first_name":"Roderich","id":"68E56E44-62B0-11EA-B963-444F3DDC885E"},{"full_name":"Bollenbach, Mark Tobias","first_name":"Mark Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X","last_name":"Bollenbach"},{"full_name":"Andersson, Dan I.","first_name":"Dan I.","last_name":"Andersson"}],"citation":{"apa":"Römhild, R., Bollenbach, M. T., &#38; Andersson, D. I. (2022). The physiology and genetics of bacterial responses to antibiotic combinations. <i>Nature Reviews Microbiology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41579-022-00700-5\">https://doi.org/10.1038/s41579-022-00700-5</a>","ieee":"R. Römhild, M. T. Bollenbach, and D. I. Andersson, “The physiology and genetics of bacterial responses to antibiotic combinations,” <i>Nature Reviews Microbiology</i>, vol. 20. Springer Nature, pp. 478–490, 2022.","chicago":"Römhild, Roderich, Mark Tobias Bollenbach, and Dan I. Andersson. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” <i>Nature Reviews Microbiology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41579-022-00700-5\">https://doi.org/10.1038/s41579-022-00700-5</a>.","short":"R. Römhild, M.T. Bollenbach, D.I. Andersson, Nature Reviews Microbiology 20 (2022) 478–490.","mla":"Römhild, Roderich, et al. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” <i>Nature Reviews Microbiology</i>, vol. 20, Springer Nature, 2022, pp. 478–90, doi:<a href=\"https://doi.org/10.1038/s41579-022-00700-5\">10.1038/s41579-022-00700-5</a>.","ama":"Römhild R, Bollenbach MT, Andersson DI. The physiology and genetics of bacterial responses to antibiotic combinations. <i>Nature Reviews Microbiology</i>. 2022;20:478-490. doi:<a href=\"https://doi.org/10.1038/s41579-022-00700-5\">10.1038/s41579-022-00700-5</a>","ista":"Römhild R, Bollenbach MT, Andersson DI. 2022. The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. 20, 478–490."},"article_processing_charge":"No","day":"01","publication_status":"published","volume":20,"date_published":"2022-08-01T00:00:00Z","doi":"10.1038/s41579-022-00700-5","publication_identifier":{"eissn":["1740-1534"],"issn":["1740-1526"]},"scopus_import":"1","department":[{"_id":"CaGu"}],"_id":"10812","keyword":["General Immunology and Microbiology","Microbiology","Infectious Diseases"],"external_id":{"pmid":["35241807"],"isi":["000763891900001"]},"year":"2022","month":"08","type":"journal_article","acknowledgement":"The authors thank B. Kavčič and H. Schulenburg for constructive feedback on the manuscript.","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"The physiology and genetics of bacterial responses to antibiotic combinations","abstract":[{"text":"Several promising strategies based on combining or cycling different antibiotics have been proposed to increase efficacy and counteract resistance evolution, but we still lack a deep understanding of the physiological responses and genetic mechanisms that underlie antibiotic interactions and the clinical applicability of these strategies. In antibiotic-exposed bacteria, the combined effects of physiological stress responses and emerging resistance mutations (occurring at different time scales) generate complex and often unpredictable dynamics. In this Review, we present our current understanding of bacterial cell physiology and genetics of responses to antibiotics. We emphasize recently discovered mechanisms of synergistic and antagonistic drug interactions, hysteresis in temporal interactions between antibiotics that arise from microbial physiology and interactions between antibiotics and resistance mutations that can cause collateral sensitivity or cross-resistance. We discuss possible connections between the different phenomena and indicate relevant research directions. A better and more unified understanding of drug and genetic interactions is likely to advance antibiotic therapy.","lang":"eng"}],"pmid":1},{"external_id":{"isi":["001044208400004"],"pmid":["35303737"]},"year":"2022","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"month":"03","type":"journal_article","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.","article_number":"e1009950","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","title":"Parameter inference for stochastic biochemical models from perturbation experiments parallelised at the single cell level","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."}],"pmid":1,"file_date_updated":"2022-04-04T10:14:39Z","doi":"10.1371/journal.pcbi.1009950","publication_identifier":{"issn":["1553-734X"],"eissn":["1553-7358"]},"issue":"3","scopus_import":"1","department":[{"_id":"CaGu"}],"_id":"10939","article_processing_charge":"No","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>","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>.","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>.","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.","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)."},"day":"18","publication_status":"published","ddc":["570","000"],"volume":18,"date_published":"2022-03-18T00:00:00Z","has_accepted_license":"1","publisher":"Public Library of Science","date_created":"2022-04-03T22:01:42Z","publication":"PLoS Computational Biology","language":[{"iso":"eng"}],"oa_version":"Published Version","related_material":{"link":[{"url":"https://gitlab.pasteur.fr/adavidov/inferencelnakf","relation":"software"}]},"article_type":"original","date_updated":"2025-09-09T14:29:53Z","intvolume":"        18","quality_controlled":"1","status":"public","isi":1,"file":[{"checksum":"458ef542761fb714ced214f240daf6b2","file_name":"2022_PLoSCompBio_Davidovic.pdf","file_id":"10947","access_level":"open_access","date_created":"2022-04-04T10:14:39Z","content_type":"application/pdf","file_size":2958642,"creator":"dernst","relation":"main_file","success":1,"date_updated":"2022-04-04T10:14:39Z"}],"author":[{"last_name":"Davidović","first_name":"Anđela","full_name":"Davidović, Anđela"},{"last_name":"Chait","orcid":"0000-0003-0876-3187","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","first_name":"Remy P","full_name":"Chait, Remy P"},{"first_name":"Gregory","full_name":"Batt, Gregory","last_name":"Batt"},{"full_name":"Ruess, Jakob","first_name":"Jakob","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1615-3282","last_name":"Ruess"}],"oa":1},{"file_date_updated":"2022-05-02T06:26:26Z","scopus_import":"1","publication_identifier":{"eissn":["2399-3642"]},"doi":"10.1038/s42003-022-03336-6","_id":"11339","department":[{"_id":"CaGu"}],"tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"year":"2022","external_id":{"isi":["000784143400001"],"pmid":["35444215"]},"type":"journal_article","month":"04","article_number":"385","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).","pmid":1,"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"}],"title":"Nutrient and salt depletion synergistically boosts glucose metabolism in individual Escherichia coli cells","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","language":[{"iso":"eng"}],"publication":"Communications Biology","publisher":"Springer Nature","date_created":"2022-05-01T22:01:41Z","article_type":"original","oa_version":"Published Version","intvolume":"         5","quality_controlled":"1","date_updated":"2023-08-03T06:45:26Z","author":[{"full_name":"Glover, Georgina","first_name":"Georgina","last_name":"Glover"},{"last_name":"Voliotis","full_name":"Voliotis, Margaritis","first_name":"Margaritis"},{"last_name":"Łapińska","first_name":"Urszula","full_name":"Łapińska, Urszula"},{"first_name":"Brandon M.","full_name":"Invergo, Brandon M.","last_name":"Invergo"},{"last_name":"Soanes","full_name":"Soanes, Darren","first_name":"Darren"},{"first_name":"Paul","full_name":"O’Neill, Paul","last_name":"O’Neill"},{"full_name":"Moore, Karen","first_name":"Karen","last_name":"Moore"},{"id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","full_name":"Nikolic, Nela","first_name":"Nela","last_name":"Nikolic","orcid":"0000-0001-9068-6090"},{"full_name":"Petrov, Peter","first_name":"Peter","last_name":"Petrov"},{"first_name":"David S.","full_name":"Milner, David S.","last_name":"Milner"},{"last_name":"Roy","full_name":"Roy, Sumita","first_name":"Sumita"},{"full_name":"Heesom, Kate","first_name":"Kate","last_name":"Heesom"},{"first_name":"Thomas A.","full_name":"Richards, Thomas A.","last_name":"Richards"},{"last_name":"Tsaneva-Atanasova","full_name":"Tsaneva-Atanasova, Krasimira","first_name":"Krasimira"},{"last_name":"Pagliara","first_name":"Stefano","full_name":"Pagliara, Stefano"}],"oa":1,"file":[{"file_id":"11342","file_name":"2022_CommBiology_Glover.pdf","checksum":"7c6f76ab17393d650825cc240edc84b3","date_created":"2022-05-02T06:26:26Z","access_level":"open_access","file_size":2827723,"content_type":"application/pdf","success":1,"date_updated":"2022-05-02T06:26:26Z","relation":"main_file","creator":"dernst"}],"isi":1,"status":"public","volume":5,"day":"20","ddc":["570"],"publication_status":"published","article_processing_charge":"No","citation":{"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>.","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).","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>.","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.","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>"},"date_published":"2022-04-20T00:00:00Z","has_accepted_license":"1"},{"title":"Quantifying heterologous gene expression during ectopic MazF production in Escherichia coli","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","pmid":1,"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."}],"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.","article_number":"173","type":"journal_article","month":"05","year":"2022","external_id":{"pmid":["35562780"]},"tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"keyword":["General Biochemistry","Genetics and Molecular Biology","General Medicine"],"department":[{"_id":"CaGu"}],"_id":"11713","doi":"10.1186/s13104-022-06061-9","publication_identifier":{"issn":["1756-0500"]},"scopus_import":"1","file_date_updated":"2022-08-01T09:24:42Z","has_accepted_license":"1","corr_author":"1","project":[{"name":"Bacterial toxin-antitoxin systems as antiphage defense mechanisms","_id":"26956E74-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"V00738"}],"date_published":"2022-05-13T00:00:00Z","day":"13","publication_status":"published","ddc":["570"],"citation":{"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>","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>.","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.","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>.","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.","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>"},"article_processing_charge":"No","volume":15,"status":"public","author":[{"last_name":"Nikolic","orcid":"0000-0001-9068-6090","id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","first_name":"Nela","full_name":"Nikolic, Nela"},{"first_name":"Martina","full_name":"Sauert, Martina","last_name":"Sauert"},{"last_name":"Albanese","first_name":"Tanino G.","full_name":"Albanese, Tanino G."},{"full_name":"Moll, Isabella","first_name":"Isabella","last_name":"Moll"}],"oa":1,"file":[{"content_type":"application/pdf","file_size":1545310,"relation":"main_file","creator":"dernst","date_updated":"2022-08-01T09:24:42Z","success":1,"file_name":"2022_BMCResearchNotes_Nikolic.pdf","checksum":"008156e5340e9789f0f6d82bde4d347a","file_id":"11714","access_level":"open_access","date_created":"2022-08-01T09:24:42Z"}],"date_updated":"2025-04-14T09:24:53Z","quality_controlled":"1","intvolume":"        15","related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1186/s13104-022-06152-7"}]},"oa_version":"Published Version","article_type":"letter_note","date_created":"2022-08-01T09:04:27Z","publisher":"Springer Nature","language":[{"iso":"eng"}],"publication":"BMC Research Notes"},{"_id":"11843","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"department":[{"_id":"MiSi"},{"_id":"CaGu"}],"ec_funded":1,"file_date_updated":"2022-08-16T08:57:37Z","scopus_import":"1","publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/eLife.78995","article_number":"e78995","acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89, and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373), and the Austrian Science Fund (FWF P29911) to MS.","abstract":[{"lang":"eng","text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both rate-limiting factors of T cell activation. This response was binary at the single-cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease."}],"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"external_id":{"pmid":["35881547"],"isi":["000838410200001"]},"year":"2022","month":"07","type":"journal_article","quality_controlled":"1","intvolume":"        11","date_updated":"2025-04-15T07:17:32Z","file":[{"date_created":"2022-08-16T08:57:37Z","access_level":"open_access","file_id":"11861","file_name":"2022_eLife_Tomasek.pdf","checksum":"002a3c7c7ea5caa9af9cfbea308f6ea4","date_updated":"2022-08-16T08:57:37Z","success":1,"creator":"cchlebak","relation":"main_file","content_type":"application/pdf","file_size":2057577}],"isi":1,"author":[{"orcid":"0000-0003-3768-877X","last_name":"Tomasek","first_name":"Kathrin","full_name":"Tomasek, Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87"},{"id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","first_name":"Alexander F","full_name":"Leithner, Alexander F","last_name":"Leithner","orcid":"0000-0002-1073-744X"},{"last_name":"Glatzová","full_name":"Glatzová, Ivana","first_name":"Ivana","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d"},{"first_name":"Michael S.","full_name":"Lukesch, Michael S.","last_name":"Lukesch"},{"last_name":"Guet","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","first_name":"Calin C"},{"first_name":"Michael K","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","orcid":"0000-0002-6620-9179"}],"oa":1,"status":"public","publication":"eLife","language":[{"iso":"eng"}],"publisher":"eLife Sciences Publications","date_created":"2022-08-14T22:01:46Z","article_type":"original","oa_version":"Published Version","related_material":{"record":[{"relation":"earlier_version","id":"10316","status":"public"}]},"has_accepted_license":"1","volume":11,"article_processing_charge":"Yes","citation":{"short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, ELife 11 (2022).","ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. eLife. 11, e78995.","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>, vol. 11, e78995, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>.","chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>.","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>"},"ddc":["570"],"day":"26","publication_status":"published","project":[{"call_identifier":"H2020","grant_number":"724373","name":"Cellular Navigation Along Spatial Gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","grant_number":"P29911","name":"Mechanical adaptation of lamellipodial actin","_id":"26018E70-B435-11E9-9278-68D0E5697425"}],"date_published":"2022-07-26T00:00:00Z","corr_author":"1"},{"intvolume":"        11","quality_controlled":"1","date_updated":"2025-03-06T14:03:50Z","oa":1,"author":[{"full_name":"Tomanek, Isabella","first_name":"Isabella","id":"3981F020-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6197-363X","last_name":"Tomanek"},{"orcid":"0000-0001-6220-2052","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","first_name":"Calin C"}],"file":[{"access_level":"open_access","date_created":"2023-01-23T08:56:21Z","file_name":"2022_eLife_Tomanek.pdf","checksum":"9321fd5f06ff59d5e2d33daee84b3da1","file_id":"12338","creator":"dernst","relation":"main_file","date_updated":"2023-01-23T08:56:21Z","success":1,"content_type":"application/pdf","file_size":8835954}],"isi":1,"status":"public","language":[{"iso":"eng"}],"publication":"eLife","date_created":"2023-01-22T23:00:55Z","publisher":"eLife Sciences Publications","article_type":"original","related_material":{"record":[{"relation":"research_data","id":"12339","status":"public"}],"link":[{"relation":"software","url":"https://doi.org/10.5281/zenodo.6974122"}]},"oa_version":"Published Version","has_accepted_license":"1","volume":11,"ddc":["570"],"publication_status":"published","day":"22","citation":{"short":"I. Tomanek, C.C. Guet, ELife 11 (2022).","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>.","ista":"Tomanek I, Guet CC. 2022. Adaptation dynamics between copynumber and point mutations. eLife. 11, e82240.","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>","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>","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>."},"article_processing_charge":"No","date_published":"2022-12-22T00:00:00Z","corr_author":"1","_id":"12333","department":[{"_id":"CaGu"}],"file_date_updated":"2023-01-23T08:56:21Z","scopus_import":"1","doi":"10.7554/ELIFE.82240","publication_identifier":{"eissn":["2050-084X"]},"article_number":"e82240","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.","pmid":1,"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."}],"title":"Adaptation dynamics between copynumber and point mutations","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"year":"2022","external_id":{"pmid":["36546673"],"isi":["000912674700001"]},"type":"journal_article","month":"12"},{"corr_author":"1","month":"12","type":"research_data_reference","date_published":"2022-12-23T00:00:00Z","article_processing_charge":"No","citation":{"apa":"Tomanek, I., &#38; Guet, C. C. (2022). Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose. Dryad. <a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">https://doi.org/10.5061/dryad.rfj6q57ds</a>","ieee":"I. Tomanek and C. C. Guet, “Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose.” Dryad, 2022.","chicago":"Tomanek, Isabella, and Calin C Guet. “Flow Cytometry YFP and CFP Data and Deep Sequencing Data of Populations Evolving in Galactose.” Dryad, 2022. <a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">https://doi.org/10.5061/dryad.rfj6q57ds</a>.","mla":"Tomanek, Isabella, and Calin C. Guet. <i>Flow Cytometry YFP and CFP Data and Deep Sequencing Data of Populations Evolving in Galactose</i>. Dryad, 2022, doi:<a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">10.5061/dryad.rfj6q57ds</a>.","ama":"Tomanek I, Guet CC. Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose. 2022. doi:<a href=\"https://doi.org/10.5061/dryad.rfj6q57ds\">10.5061/dryad.rfj6q57ds</a>","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>.","short":"I. Tomanek, C.C. Guet, (2022)."},"ddc":["570"],"day":"23","year":"2022","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Flow cytometry YFP and CFP data and deep sequencing data of populations evolving in galactose","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."}],"related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"12333"}]},"oa_version":"Published Version","doi":"10.5061/dryad.rfj6q57ds","publisher":"Dryad","date_created":"2023-01-23T09:00:37Z","status":"public","oa":1,"author":[{"orcid":"0000-0001-6197-363X","last_name":"Tomanek","full_name":"Tomanek, Isabella","first_name":"Isabella","id":"3981F020-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-6220-2052","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","full_name":"Guet, Calin C"}],"date_updated":"2025-03-06T14:03:50Z","department":[{"_id":"CaGu"}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.5061/dryad.rfj6q57ds"}],"_id":"12339"}]