[{"citation":{"mla":"Grah, Rok, et al. “Normative Models of Enhancer Function.” BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.08.029405.","short":"R. Grah, B. Zoller, G. Tkačik, BioRxiv (2020).","ista":"Grah R, Zoller B, Tkačik G. 2020. Normative models of enhancer function. bioRxiv, 10.1101/2020.04.08.029405.","chicago":"Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Normative Models of Enhancer Function.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.04.08.029405.","apa":"Grah, R., Zoller, B., & Tkačik, G. (2020). Normative models of enhancer function. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.04.08.029405","ama":"Grah R, Zoller B, Tkačik G. Normative models of enhancer function. bioRxiv. 2020. doi:10.1101/2020.04.08.029405","ieee":"R. Grah, B. Zoller, and G. Tkačik, “Normative models of enhancer function,” bioRxiv. Cold Spring Harbor Laboratory, 2020."},"publisher":"Cold Spring Harbor Laboratory","date_created":"2020-04-23T10:12:51Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"status":"public","month":"04","article_processing_charge":"No","date_published":"2020-04-09T00:00:00Z","date_updated":"2026-04-08T07:25:08Z","project":[{"grant_number":"RGP0034/2018","_id":"2665AAFE-B435-11E9-9278-68D0E5697425","name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?"},{"_id":"267C84F4-B435-11E9-9278-68D0E5697425","name":"Biophysically realistic genotype-phenotype maps for regulatory networks"}],"type":"preprint","publication":"bioRxiv","_id":"7675","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2020.04.08.029405 "}],"author":[{"last_name":"Grah","first_name":"Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2539-3560","full_name":"Grah, Rok"},{"full_name":"Zoller, Benjamin","first_name":"Benjamin","last_name":"Zoller"},{"orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik","first_name":"Gašper"}],"publication_status":"published","oa_version":"Preprint","related_material":{"record":[{"status":"public","id":"8155","relation":"dissertation_contains"}]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","doi":"10.1101/2020.04.08.029405","title":"Normative models of enhancer function","year":"2020","day":"09","oa":1,"abstract":[{"text":"In prokaryotes, thermodynamic models of gene regulation provide a highly quantitative mapping from promoter sequences to gene expression levels that is compatible with in vivo and in vitro bio-physical measurements. Such concordance has not been achieved for models of enhancer function in eukaryotes. In equilibrium models, it is difficult to reconcile the reported short transcription factor (TF) residence times on the DNA with the high specificity of regulation. In non-equilibrium models, progress is difficult due to an explosion in the number of parameters. Here, we navigate this complexity by looking for minimal non-equilibrium enhancer models that yield desired regulatory phenotypes: low TF residence time, high specificity and tunable cooperativity. We find that a single extra parameter, interpretable as the “linking rate” by which bound TFs interact with Mediator components, enables our models to escape equilibrium bounds and access optimal regulatory phenotypes, while remaining consistent with the reported phenomenology and simple enough to be inferred from upcoming experiments. We further find that high specificity in non-equilibrium models is in a tradeoff with gene expression noise, predicting bursty dynamics — an experimentally-observed hallmark of eukaryotic transcription. By drastically reducing the vast parameter space to a much smaller subspace that optimally realizes biological function prior to inference from data, our normative approach holds promise for mathematical models in systems biology.","lang":"eng"}],"corr_author":"1","language":[{"iso":"eng"}]},{"oa_version":"None","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","pmid":1,"author":[{"full_name":"Kainrath, Stephanie","id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6709-2195","first_name":"Stephanie","last_name":"Kainrath"},{"last_name":"Janovjak","first_name":"Harald L","orcid":"0000-0002-8023-9315","full_name":"Janovjak, Harald L","id":"33BA6C30-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"pmid":["32651922"]},"status":"public","month":"07","page":"233-246","date_created":"2020-07-26T22:01:03Z","department":[{"_id":"CaGu"}],"citation":{"chicago":"Kainrath, Stephanie, and Harald L Janovjak. “Design and Application of Light-Regulated Receptor Tyrosine Kinases.” In Photoswitching Proteins, edited by Dominik Niopek, 2173:233–46. MIMB. Springer Nature, 2020. https://doi.org/10.1007/978-1-0716-0755-8_16.","ista":"Kainrath S, Janovjak HL. 2020.Design and application of light-regulated receptor tyrosine kinases. In: Photoswitching Proteins. Methods in Molecular Biology, vol. 2173, 233–246.","mla":"Kainrath, Stephanie, and Harald L. Janovjak. “Design and Application of Light-Regulated Receptor Tyrosine Kinases.” Photoswitching Proteins, edited by Dominik Niopek, vol. 2173, Springer Nature, 2020, pp. 233–46, doi:10.1007/978-1-0716-0755-8_16.","short":"S. Kainrath, H.L. Janovjak, in:, D. Niopek (Ed.), Photoswitching Proteins, Springer Nature, 2020, pp. 233–246.","ama":"Kainrath S, Janovjak HL. Design and application of light-regulated receptor tyrosine kinases. In: Niopek D, ed. Photoswitching Proteins. Vol 2173. MIMB. Springer Nature; 2020:233-246. doi:10.1007/978-1-0716-0755-8_16","apa":"Kainrath, S., & Janovjak, H. L. (2020). Design and application of light-regulated receptor tyrosine kinases. In D. Niopek (Ed.), Photoswitching Proteins (Vol. 2173, pp. 233–246). Springer Nature. https://doi.org/10.1007/978-1-0716-0755-8_16","ieee":"S. Kainrath and H. L. Janovjak, “Design and application of light-regulated receptor tyrosine kinases,” in Photoswitching Proteins, vol. 2173, D. Niopek, Ed. Springer Nature, 2020, pp. 233–246."},"publisher":"Springer Nature","intvolume":" 2173","publication_identifier":{"issn":["1064-3745"],"eisbn":["9781071607558"],"eissn":["1940-6029"],"isbn":["9781071607541"]},"_id":"8173","date_published":"2020-07-11T00:00:00Z","doi":"10.1007/978-1-0716-0755-8_16","publication_status":"published","language":[{"iso":"eng"}],"abstract":[{"text":"Understanding how the activity of membrane receptors and cellular signaling pathways shapes cell behavior is of fundamental interest in basic and applied research. Reengineering receptors to react to light instead of their cognate ligands allows for generating defined signaling inputs with high spatial and temporal precision and facilitates the dissection of complex signaling networks. Here, we describe fundamental considerations in the design of light-regulated receptor tyrosine kinases (Opto-RTKs) and appropriate control experiments. We also introduce methods for transient receptor expression in HEK293 cells, quantitative assessment of signaling activity in reporter gene assays, semiquantitative assessment of (in)activation time courses through Western blot (WB) analysis, and easy to implement light stimulation hardware.","lang":"eng"}],"day":"11","title":"Design and application of light-regulated receptor tyrosine kinases","volume":2173,"year":"2020","alternative_title":["Methods in Molecular Biology"],"editor":[{"last_name":"Niopek","first_name":"Dominik","full_name":"Niopek, Dominik"}],"article_processing_charge":"No","series_title":"MIMB","scopus_import":"1","date_updated":"2026-04-16T09:22:45Z","publication":"Photoswitching Proteins","type":"book_chapter"},{"doi":"10.15479/AT:ISTA:7680","publication_status":"published","file_date_updated":"2021-10-31T23:30:05Z","language":[{"iso":"eng"}],"supervisor":[{"id":"33BA6C30-F248-11E8-B48F-1D18A9856A87","full_name":"Janovjak, Harald L","orcid":"0000-0002-8023-9315","first_name":"Harald L","last_name":"Janovjak"}],"abstract":[{"lang":"eng","text":"Proteins and their complex dynamic interactions regulate cellular mechanisms from sensing and transducing extracellular signals, to mediating genetic responses, and sustaining or changing cell morphology. To manipulate these protein-protein interactions (PPIs) that govern the behavior and fate of cells, synthetically constructed, genetically encoded tools provide the means to precisely target proteins of interest (POIs), and control their subcellular localization and activity in vitro and in vivo. Ideal synthetic tools react to an orthogonal cue, i.e. a trigger that does not activate any other endogenous process, thereby allowing manipulation of the POI alone.\r\nIn optogenetics, naturally occurring photosensory domain from plants, algae and bacteria are re-purposed and genetically fused to POIs. Illumination with light of a specific wavelength triggers a conformational change that can mediate PPIs, such as dimerization or oligomerization. By using light as a trigger, these tools can be activated with high spatial and temporal precision, on subcellular and millisecond scales. Chemogenetic tools consist of protein domains that recognize and bind small molecules. By genetic fusion to POIs, these domains can mediate PPIs upon addition of their specific ligands, which are often synthetically designed to provide highly specific interactions and exhibit good bioavailability.\r\nMost optogenetic tools to mediate PPIs are based on well-studied photoreceptors responding to red, blue or near-UV light, leaving a striking gap in the green band of the visible light spectrum. Among both optogenetic and chemogenetic tools, there is an abundance of methods to induce PPIs, but tools to disrupt them require UV illumination, rely on covalent linkage and subsequent enzymatic cleavage or initially result in protein clustering of unknown stoichiometry.\r\nThis work describes how the recently structurally and photochemically characterized green-light responsive cobalamin-binding domains (CBDs) from bacterial transcription factors were re-purposed to function as a green-light responsive optogenetic tool. In contrast to previously engineered optogenetic tools, CBDs do not induce PPI, but rather confer a PPI already upon expression, which can be rapidly disrupted by illumination. This was employed to mimic inhibition of constitutive activity of a growth factor receptor, and successfully implement for cell signalling in mammalian cells and in vivo to rescue development in zebrafish. This work further describes the development and application of a chemically induced de-dimerizer (CDD) based on a recently identified and structurally described bacterial oxyreductase. CDD forms a dimer upon expression in absence of its cofactor, the flavin derivative F420. Safety and of domain expression and ligand exposure are demonstrated in vitro and in vivo in zebrafish. The system is further applied to inhibit cell signalling output from a chimeric receptor upon F420 treatment.\r\nCBDs and CDD expand the repertoire of synthetic tools by providing novel mechanisms of mediating PPIs, and by recognizing previously not utilized cues. In the future, they can readily be combined with existing synthetic tools to functionally manipulate PPIs in vitro and in vivo."}],"corr_author":"1","oa":1,"day":"24","alternative_title":["ISTA Thesis"],"year":"2020","title":"Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals","article_processing_charge":"No","degree_awarded":"PhD","ddc":["570"],"type":"dissertation","date_updated":"2025-11-03T23:30:47Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"None","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"1028"}]},"author":[{"id":"32CFBA64-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6709-2195","full_name":"Kainrath, Stephanie","first_name":"Stephanie","last_name":"Kainrath"}],"file":[{"file_id":"7692","date_updated":"2021-10-31T23:30:05Z","content_type":"application/pdf","creator":"stgingl","access_level":"open_access","relation":"main_file","date_created":"2020-04-28T11:19:21Z","file_name":"Thesis_without-signatures_PDFA.pdf","file_size":3268017,"checksum":"fb9a4468eb27be92690728e35c823796","embargo":"2021-10-30"},{"embargo_to":"open_access","file_name":"Thesis_without signatures.docx","file_size":5167703,"checksum":"f6c80ca97104a631a328cb79a2c53493","date_created":"2020-04-28T11:19:24Z","access_level":"closed","relation":"source_file","creator":"stgingl","content_type":"application/octet-stream","date_updated":"2021-10-31T23:30:05Z","file_id":"7693"}],"has_accepted_license":"1","month":"04","status":"public","page":"98","date_created":"2020-04-24T16:00:51Z","department":[{"_id":"CaGu"}],"citation":{"short":"S. Kainrath, Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals, Institute of Science and Technology Austria, 2020.","mla":"Kainrath, Stephanie. Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:7680.","ista":"Kainrath S. 2020. Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. Institute of Science and Technology Austria.","chicago":"Kainrath, Stephanie. “Synthetic Tools for Optogenetic and Chemogenetic Inhibition of Cellular Signals.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:7680.","ama":"Kainrath S. Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. 2020. doi:10.15479/AT:ISTA:7680","ieee":"S. Kainrath, “Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals,” Institute of Science and Technology Austria, 2020.","apa":"Kainrath, S. (2020). Synthetic tools for optogenetic and chemogenetic inhibition of cellular signals. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7680"},"publisher":"Institute of Science and Technology Austria","_id":"7680","publication_identifier":{"eissn":["2663-337X"]},"date_published":"2020-04-24T00:00:00Z"},{"file_date_updated":"2020-10-09T09:56:01Z","doi":"10.1038/s41559-020-1132-7","publication_status":"published","oa":1,"day":"01","year":"2020","title":"Gene amplification as a form of population-level gene expression regulation","volume":4,"language":[{"iso":"eng"}],"abstract":[{"text":"Organisms cope with change by taking advantage of transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. Here, we investigate whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using real-time monitoring of gene-copy-number mutations in Escherichia coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy-number and, therefore, expression-level polymorphisms. This amplification-mediated gene expression tuning (AMGET) occurs on timescales that are similar to canonical gene regulation and can respond to rapid environmental changes. Mathematical modelling shows that amplifications also tune gene expression in stochastic environments in which transcription-factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune the expression of any gene, without leaving any genomic signature.","lang":"eng"}],"article_processing_charge":"No","article_type":"original","publication":"Nature Ecology & Evolution","type":"journal_article","date_updated":"2026-05-03T22:30:50Z","scopus_import":"1","ddc":["570"],"isi":1,"external_id":{"isi":["000519008300005"],"pmid":["32152532"]},"author":[{"full_name":"Tomanek, Isabella","id":"3981F020-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6197-363X","first_name":"Isabella","last_name":"Tomanek"},{"id":"483E70DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2539-3560","full_name":"Grah, Rok","first_name":"Rok","last_name":"Grah"},{"full_name":"Lagator, M.","last_name":"Lagator","first_name":"M."},{"full_name":"Andersson, A. M. C.","first_name":"A. M. C.","last_name":"Andersson"},{"id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612","full_name":"Bollback, Jonathan P","last_name":"Bollback","first_name":"Jonathan P"},{"orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","last_name":"Tkačik"},{"first_name":"Calin C","last_name":"Guet","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052"}],"pmid":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/how-to-thrive-without-gene-regulation/"}],"record":[{"relation":"research_data","status":"public","id":"7016"},{"id":"7383","status":"public","relation":"research_data"},{"status":"public","id":"8155","relation":"dissertation_contains"},{"relation":"used_in_publication","status":"public","id":"8653"}]},"oa_version":"Submitted Version","file":[{"file_id":"8640","date_updated":"2020-10-09T09:56:01Z","content_type":"application/pdf","creator":"dernst","access_level":"open_access","relation":"main_file","date_created":"2020-10-09T09:56:01Z","file_name":"2020_NatureEcolEvo_Tomanek.pdf","success":1,"checksum":"ef3bbf42023e30b2c24a6278025d2040","file_size":745242}],"acknowledgement":"We thank L. Hurst, N. Barton, M. Pleska, M. Steinrück, B. Kavcic and A. Staron for input on the manuscript, and To. Bergmiller and R. Chait for help with microfluidics experiments. I.T. is a recipient the OMV fellowship. R.G. is a recipient of a DOC (Doctoral Fellowship Programme of the Austrian Academy of Sciences) Fellowship of the Austrian Academy of Sciences.","has_accepted_license":"1","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"date_created":"2020-04-08T15:20:53Z","publisher":"Springer Nature","citation":{"ama":"Tomanek I, Grah R, Lagator M, et al. Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. 2020;4(4):612-625. doi:10.1038/s41559-020-1132-7","apa":"Tomanek, I., Grah, R., Lagator, M., Andersson, A. M. C., Bollback, J. P., Tkačik, G., & Guet, C. C. (2020). Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. Springer Nature. https://doi.org/10.1038/s41559-020-1132-7","ieee":"I. Tomanek et al., “Gene amplification as a form of population-level gene expression regulation,” Nature Ecology & Evolution, vol. 4, no. 4. Springer Nature, pp. 612–625, 2020.","ista":"Tomanek I, Grah R, Lagator M, Andersson AMC, Bollback JP, Tkačik G, Guet CC. 2020. Gene amplification as a form of population-level gene expression regulation. Nature Ecology & Evolution. 4(4), 612–625.","short":"I. Tomanek, R. Grah, M. Lagator, A.M.C. Andersson, J.P. Bollback, G. Tkačik, C.C. Guet, Nature Ecology & Evolution 4 (2020) 612–625.","mla":"Tomanek, Isabella, et al. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Nature Ecology & Evolution, vol. 4, no. 4, Springer Nature, 2020, pp. 612–25, doi:10.1038/s41559-020-1132-7.","chicago":"Tomanek, Isabella, Rok Grah, M. Lagator, A. M. C. Andersson, Jonathan P Bollback, Gašper Tkačik, and Calin C Guet. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Nature Ecology & Evolution. Springer Nature, 2020. https://doi.org/10.1038/s41559-020-1132-7."},"month":"04","status":"public","page":"612-625","project":[{"_id":"267C84F4-B435-11E9-9278-68D0E5697425","name":"Biophysically realistic genotype-phenotype maps for regulatory networks"}],"quality_controlled":"1","date_published":"2020-04-01T00:00:00Z","_id":"7652","publication_identifier":{"issn":["2397-334X"]},"issue":"4","intvolume":" 4"},{"ddc":["576"],"degree_awarded":"PhD","date_updated":"2026-04-08T07:29:19Z","type":"dissertation","article_processing_charge":"No","abstract":[{"lang":"eng","text":"Mutations are the raw material of evolution and come in many different flavors. Point mutations change a single letter in the DNA sequence, while copy number mutations like duplications or deletions add or remove many letters of the DNA sequence simultaneously. Each type of mutation exhibits specific properties like its rate of formation and reversal. \r\nGene expression is a fundamental phenotype that can be altered by both, point and copy number mutations. The following thesis is concerned with the dynamics of gene expression evolution and how it is affected by the properties exhibited by point and copy number mutations. Specifically, we are considering i) copy number mutations during adaptation to fluctuating environments and ii) the interaction of copy number and point mutations during adaptation to constant environments. "}],"supervisor":[{"orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","last_name":"Guet"}],"corr_author":"1","language":[{"iso":"eng"}],"title":"The evolution of gene expression by copy number and point mutations","year":"2020","alternative_title":["ISTA Thesis"],"day":"13","oa":1,"publication_status":"published","doi":"10.15479/AT:ISTA:8653","file_date_updated":"2021-10-20T22:30:03Z","publication_identifier":{"issn":["2663-337X"]},"_id":"8653","date_published":"2020-10-13T00:00:00Z","page":"117","status":"public","month":"10","publisher":"Institute of Science and Technology Austria","citation":{"ama":"Tomanek I. The evolution of gene expression by copy number and point mutations. 2020. doi:10.15479/AT:ISTA:8653","apa":"Tomanek, I. (2020). The evolution of gene expression by copy number and point mutations. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8653","ieee":"I. Tomanek, “The evolution of gene expression by copy number and point mutations,” Institute of Science and Technology Austria, 2020.","ista":"Tomanek I. 2020. The evolution of gene expression by copy number and point mutations. Institute of Science and Technology Austria.","short":"I. Tomanek, The Evolution of Gene Expression by Copy Number and Point Mutations, Institute of Science and Technology Austria, 2020.","mla":"Tomanek, Isabella. The Evolution of Gene Expression by Copy Number and Point Mutations. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8653.","chicago":"Tomanek, Isabella. “The Evolution of Gene Expression by Copy Number and Point Mutations.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8653."},"department":[{"_id":"CaGu"}],"date_created":"2020-10-13T13:02:33Z","has_accepted_license":"1","file":[{"creator":"itomanek","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"8666","date_updated":"2021-10-20T22:30:03Z","embargo_to":"open_access","file_name":"Thesis_ITomanek_final_201016.docx","file_size":25131884,"checksum":"c01d9f59794b4b70528f37637c17ad02","date_created":"2020-10-16T12:14:21Z","access_level":"closed","relation":"source_file"},{"date_created":"2020-10-16T12:14:21Z","relation":"main_file","access_level":"open_access","embargo":"2021-10-19","checksum":"f8edbc3b0f81a780e13ca1e561d42d8b","file_size":15405675,"file_name":"Thesis_ITomanek_final_201016.pdf","date_updated":"2021-10-20T22:30:03Z","file_id":"8667","creator":"itomanek","content_type":"application/pdf"}],"keyword":["duplication","amplification","promoter","CNV","AMGET","experimental evolution","Escherichia coli"],"oa_version":"Published Version","related_material":{"record":[{"relation":"research_data","id":"7652","status":"public"}]},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","author":[{"id":"3981F020-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6197-363X","full_name":"Tomanek, Isabella","first_name":"Isabella","last_name":"Tomanek"}],"OA_place":"publisher"},{"oa":1,"day":"01","year":"2019","title":"Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system","volume":65,"publist_id":"7785","language":[{"iso":"eng"}],"abstract":[{"text":"Autoregulation is the direct modulation of gene expression by the product of the corresponding gene. Autoregulation of bacterial gene expression has been mostly studied at the transcriptional level, when a protein acts as the cognate transcriptional repressor. A recent study investigating dynamics of the bacterial toxin–antitoxin MazEF system has shown how autoregulation at both the transcriptional and post-transcriptional levels affects the heterogeneity of Escherichia coli populations. Toxin–antitoxin systems hold a crucial but still elusive part in bacterial response to stress. This perspective highlights how these modules can also serve as a great model system for investigating basic concepts in gene regulation. However, as the genomic background and environmental conditions substantially influence toxin activation, it is important to study (auto)regulation of toxin–antitoxin systems in well-defined setups as well as in conditions that resemble the environmental niche.","lang":"eng"}],"file_date_updated":"2020-07-14T12:44:47Z","ec_funded":1,"doi":"10.1007/s00294-018-0879-8","publication_status":"published","type":"journal_article","publication":"Current Genetics","date_updated":"2025-04-15T06:50:19Z","scopus_import":"1","ddc":["570"],"article_processing_charge":"Yes (via OA deal)","file":[{"checksum":"6779708b0b632a1a6ed28c56f5161142","file_size":776399,"file_name":"2019_CurrentGenetics_Nikolic.pdf","date_created":"2019-02-06T07:50:58Z","relation":"main_file","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_id":"5930","date_updated":"2020-07-14T12:44:47Z"}],"has_accepted_license":"1","isi":1,"external_id":{"isi":["000456958800017"]},"author":[{"id":"42D9CABC-F248-11E8-B48F-1D18A9856A87","full_name":"Nikolic, Nela","orcid":"0000-0001-9068-6090","first_name":"Nela","last_name":"Nikolic"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","project":[{"grant_number":"291734","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"quality_controlled":"1","date_published":"2019-02-01T00:00:00Z","_id":"138","issue":"1","intvolume":" 65","date_created":"2018-12-11T11:44:50Z","department":[{"_id":"CaGu"}],"publisher":"Springer","citation":{"ieee":"N. Nikolic, “Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system,” Current Genetics, vol. 65, no. 1. Springer, pp. 133–138, 2019.","ama":"Nikolic N. Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system. Current Genetics. 2019;65(1):133-138. doi:10.1007/s00294-018-0879-8","apa":"Nikolic, N. (2019). Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system. Current Genetics. Springer. https://doi.org/10.1007/s00294-018-0879-8","mla":"Nikolic, Nela. “Autoregulation of Bacterial Gene Expression: Lessons from the MazEF Toxin–Antitoxin System.” Current Genetics, vol. 65, no. 1, Springer, 2019, pp. 133–38, doi:10.1007/s00294-018-0879-8.","short":"N. Nikolic, Current Genetics 65 (2019) 133–138.","ista":"Nikolic N. 2019. Autoregulation of bacterial gene expression: lessons from the MazEF toxin–antitoxin system. Current Genetics. 65(1), 133–138.","chicago":"Nikolic, Nela. “Autoregulation of Bacterial Gene Expression: Lessons from the MazEF Toxin–Antitoxin System.” Current Genetics. Springer, 2019. https://doi.org/10.1007/s00294-018-0879-8."},"month":"02","status":"public","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"page":"133-138"},{"language":[{"iso":"eng"}],"corr_author":"1","abstract":[{"text":"The abelian sandpile serves as a model to study self-organized criticality, a phenomenon occurring in biological, physical and social processes. The identity of the abelian group is a fractal composed of self-similar patches, and its limit is subject of extensive collaborative research. Here, we analyze the evolution of the sandpile identity under harmonic fields of different orders. We show that this evolution corresponds to periodic cycles through the abelian group characterized by the smooth transformation and apparent conservation of the patches constituting the identity. The dynamics induced by second and third order harmonics resemble smooth stretchings, respectively translations, of the identity, while the ones induced by fourth order harmonics resemble magnifications and rotations. Starting with order three, the dynamics pass through extended regions of seemingly random configurations which spontaneously reassemble into accentuated patterns. We show that the space of harmonic functions projects to the extended analogue of the sandpile group, thus providing a set of universal coordinates identifying configurations between different domains. Since the original sandpile group is a subgroup of the extended one, this directly implies that it admits a natural renormalization. Furthermore, we show that the harmonic fields can be induced by simple Markov processes, and that the corresponding stochastic dynamics show remarkable robustness over hundreds of periods. Finally, we encode information into seemingly random configurations, and decode this information with an algorithm requiring minimal prior knowledge. Our results suggest that harmonic fields might split the sandpile group into sub-sets showing different critical coefficients, and that it might be possible to extend the fractal structure of the identity beyond the boundaries of its domain. ","lang":"eng"}],"day":"19","oa":1,"volume":116,"title":"Harmonic dynamics of the Abelian sandpile","year":"2019","doi":"10.1073/pnas.1812015116","publication_status":"published","main_file_link":[{"url":"https://doi.org/10.1073/pnas.1812015116","open_access":"1"}],"scopus_import":"1","date_updated":"2025-06-03T11:18:16Z","type":"journal_article","publication":"Proceedings of the National Academy of Sciences of the United States of America","article_processing_charge":"No","article_type":"original","acknowledgement":"M.L. is grateful to the members of the C Guet and G Tkacik groups for valuable comments and support. M.S. is grateful to Nikita Kalinin for inspiring communications.\r\n","oa_version":"Published Version","related_material":{"link":[{"url":"https://ist.ac.at/en/news/famous-sandpile-model-shown-to-move-like-a-traveling-sand-dune/","description":"News on IST Webpage","relation":"press_release"}]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","isi":1,"pmid":1,"author":[{"first_name":"Moritz","last_name":"Lang","full_name":"Lang, Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Mikhail","last_name":"Shkolnikov","orcid":"0000-0002-4310-178X","full_name":"Shkolnikov, Mikhail","id":"35084A62-F248-11E8-B48F-1D18A9856A87"}],"arxiv":1,"external_id":{"pmid":[" 30728300"],"arxiv":["1806.10823"],"isi":["000459074400013"]},"issue":"8","publication_identifier":{"eissn":["1091-6490"]},"intvolume":" 116","_id":"196","quality_controlled":"1","date_published":"2019-02-19T00:00:00Z","status":"public","month":"02","page":"2821-2830","date_created":"2018-12-11T11:45:08Z","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"TaHa"}],"publisher":"National Academy of Sciences","citation":{"chicago":"Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.” Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 2019. https://doi.org/10.1073/pnas.1812015116.","mla":"Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.” Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 8, National Academy of Sciences, 2019, pp. 2821–30, doi:10.1073/pnas.1812015116.","short":"M. Lang, M. Shkolnikov, Proceedings of the National Academy of Sciences of the United States of America 116 (2019) 2821–2830.","ista":"Lang M, Shkolnikov M. 2019. Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences of the United States of America. 116(8), 2821–2830.","ama":"Lang M, Shkolnikov M. Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences of the United States of America. 2019;116(8):2821-2830. doi:10.1073/pnas.1812015116","ieee":"M. Lang and M. Shkolnikov, “Harmonic dynamics of the Abelian sandpile,” Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 8. National Academy of Sciences, pp. 2821–2830, 2019.","apa":"Lang, M., & Shkolnikov, M. (2019). Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences. https://doi.org/10.1073/pnas.1812015116"}},{"author":[{"orcid":"0000-0003-1615-3282","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","full_name":"Ruess, Jakob","last_name":"Ruess","first_name":"Jakob"},{"last_name":"Pleska","first_name":"Maros","orcid":"0000-0001-7460-7479","id":"4569785E-F248-11E8-B48F-1D18A9856A87","full_name":"Pleska, Maros"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"},{"last_name":"Tkačik","first_name":"Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper"}],"related_material":{"record":[{"id":"6784","status":"public","relation":"used_in_publication"}]},"oa_version":"Published Version","doi":"10.1371/journal.pcbi.1007168.s001","user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","day":"02","title":"Supporting text and results","year":"2019","date_created":"2021-08-06T08:23:43Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publisher":"Public Library of Science","citation":{"chicago":"Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Supporting Text and Results.” Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168.s001.","mla":"Ruess, Jakob, et al. Supporting Text and Results. Public Library of Science, 2019, doi:10.1371/journal.pcbi.1007168.s001.","short":"J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, (2019).","ista":"Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Supporting text and results, Public Library of Science, 10.1371/journal.pcbi.1007168.s001.","ieee":"J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Supporting text and results.” Public Library of Science, 2019.","apa":"Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Supporting text and results. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168.s001","ama":"Ruess J, Pleska M, Guet CC, Tkačik G. Supporting text and results. 2019. doi:10.1371/journal.pcbi.1007168.s001"},"status":"public","month":"07","article_processing_charge":"No","date_updated":"2025-04-15T07:33:55Z","type":"research_data_reference","date_published":"2019-07-02T00:00:00Z","_id":"9786"},{"quality_controlled":"1","project":[{"name":"Design principles underlying genetic switch architecture","_id":"251EE76E-B435-11E9-9278-68D0E5697425","grant_number":"24573"}],"date_published":"2019-06-03T00:00:00Z","_id":"6717","intvolume":" 10","date_created":"2019-07-28T21:59:18Z","department":[{"_id":"CaGu"}],"publisher":"Frontiers","citation":{"chicago":"Igler, Claudia, and Stephen T. Abedon. “Commentary: A Host-Produced Quorum-Sensing Autoinducer Controls a Phage Lysis-Lysogeny Decision.” Frontiers in Microbiology. Frontiers, 2019. https://doi.org/10.3389/fmicb.2019.01171.","ista":"Igler C, Abedon ST. 2019. Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Frontiers in Microbiology. 10, 1171.","mla":"Igler, Claudia, and Stephen T. Abedon. “Commentary: A Host-Produced Quorum-Sensing Autoinducer Controls a Phage Lysis-Lysogeny Decision.” Frontiers in Microbiology, vol. 10, 1171, Frontiers, 2019, doi:10.3389/fmicb.2019.01171.","short":"C. Igler, S.T. Abedon, Frontiers in Microbiology 10 (2019).","apa":"Igler, C., & Abedon, S. T. (2019). Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Frontiers in Microbiology. Frontiers. https://doi.org/10.3389/fmicb.2019.01171","ieee":"C. Igler and S. T. Abedon, “Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision,” Frontiers in Microbiology, vol. 10. Frontiers, 2019.","ama":"Igler C, Abedon ST. Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Frontiers in Microbiology. 2019;10. doi:10.3389/fmicb.2019.01171"},"month":"06","status":"public","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"file":[{"creator":"apreinsp","content_type":"application/pdf","date_updated":"2020-07-14T12:47:38Z","file_id":"6722","file_name":"2019_Frontiers_Igler.pdf","file_size":246151,"checksum":"317a06067e9a8e717bb55f23e0d77ba7","date_created":"2019-07-29T07:51:54Z","access_level":"open_access","relation":"main_file"}],"has_accepted_license":"1","isi":1,"external_id":{"isi":["000470131200001"]},"author":[{"id":"46613666-F248-11E8-B48F-1D18A9856A87","full_name":"Igler, Claudia","last_name":"Igler","first_name":"Claudia"},{"full_name":"Abedon, Stephen T.","first_name":"Stephen T.","last_name":"Abedon"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"Published Version","publication":"Frontiers in Microbiology","type":"journal_article","date_updated":"2025-04-14T13:38:17Z","scopus_import":"1","ddc":["570"],"article_processing_charge":"Yes (via OA deal)","oa":1,"day":"03","year":"2019","title":"Commentary: A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision","volume":10,"article_number":"1171","language":[{"iso":"eng"}],"abstract":[{"text":"With the recent publication by Silpe and Bassler (2019), considering phage detection of a bacterial quorum-sensing (QS) autoinducer, we now have as many as five examples of phage-associated intercellular communication (Table 1). Each potentially involves ecological inferences by phages as to concentrations of surrounding phage-infected or uninfected bacteria. While the utility of phage detection of bacterial QS molecules may at first glance appear to be straightforward, we suggest in this commentary that the underlying ecological explanation is unlikely to be simple.","lang":"eng"}],"file_date_updated":"2020-07-14T12:47:38Z","doi":"10.3389/fmicb.2019.01171","publication_status":"published"},{"article_type":"original","article_processing_charge":"No","ddc":["570"],"scopus_import":"1","date_updated":"2025-04-14T13:46:26Z","type":"journal_article","publication":"PLoS Computational Biology","publication_status":"published","doi":"10.1371/journal.pcbi.1007168","file_date_updated":"2020-07-14T12:47:40Z","abstract":[{"lang":"eng","text":"Mathematical models have been used successfully at diverse scales of biological organization, ranging from ecology and population dynamics to stochastic reaction events occurring between individual molecules in single cells. Generally, many biological processes unfold across multiple scales, with mutations being the best studied example of how stochasticity at the molecular scale can influence outcomes at the population scale. In many other contexts, however, an analogous link between micro- and macro-scale remains elusive, primarily due to the challenges involved in setting up and analyzing multi-scale models. Here, we employ such a model to investigate how stochasticity propagates from individual biochemical reaction events in the bacterial innate immune system to the ecology of bacteria and bacterial viruses. We show analytically how the dynamics of bacterial populations are shaped by the activities of immunity-conferring enzymes in single cells and how the ecological consequences imply optimal bacterial defense strategies against viruses. Our results suggest that bacterial populations in the presence of viruses can either optimize their initial growth rate or their population size, with the first strategy favoring simple immunity featuring a single restriction modification system and the second strategy favoring complex bacterial innate immunity featuring several simultaneously active restriction modification systems."}],"language":[{"iso":"eng"}],"article_number":"e1007168","volume":15,"title":"Molecular noise of innate immunity shapes bacteria-phage ecologies","year":"2019","day":"02","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"status":"public","month":"07","citation":{"chicago":"Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” PLoS Computational Biology. Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168.","mla":"Ruess, Jakob, et al. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” PLoS Computational Biology, vol. 15, no. 7, e1007168, Public Library of Science, 2019, doi:10.1371/journal.pcbi.1007168.","short":"J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, PLoS Computational Biology 15 (2019).","ista":"Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Molecular noise of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology. 15(7), e1007168.","ama":"Ruess J, Pleska M, Guet CC, Tkačik G. Molecular noise of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology. 2019;15(7). doi:10.1371/journal.pcbi.1007168","ieee":"J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Molecular noise of innate immunity shapes bacteria-phage ecologies,” PLoS Computational Biology, vol. 15, no. 7. Public Library of Science, 2019.","apa":"Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Molecular noise of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168"},"publisher":"Public Library of Science","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"date_created":"2019-08-11T21:59:19Z","publication_identifier":{"eissn":["1553-7358"]},"intvolume":" 15","issue":"7","_id":"6784","date_published":"2019-07-02T00:00:00Z","project":[{"grant_number":"24210","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level","_id":"251D65D8-B435-11E9-9278-68D0E5697425"},{"_id":"251BCBEC-B435-11E9-9278-68D0E5697425","name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems","grant_number":"RGY0079/2011"}],"quality_controlled":"1","related_material":{"record":[{"id":"9786","status":"public","relation":"research_data"}]},"oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"full_name":"Ruess, Jakob","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1615-3282","last_name":"Ruess","first_name":"Jakob"},{"id":"4569785E-F248-11E8-B48F-1D18A9856A87","full_name":"Pleska, Maros","orcid":"0000-0001-7460-7479","first_name":"Maros","last_name":"Pleska"},{"last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","first_name":"Gašper","last_name":"Tkačik"}],"external_id":{"isi":["000481577700032"]},"isi":1,"has_accepted_license":"1","file":[{"relation":"main_file","access_level":"open_access","date_created":"2019-08-12T12:27:26Z","checksum":"7ded4721b41c2a0fc66a1c634540416a","file_size":2200003,"file_name":"2019_PlosComputBiology_Ruess.pdf","file_id":"6803","date_updated":"2020-07-14T12:47:40Z","content_type":"application/pdf","creator":"dernst"}]},{"_id":"7016","ddc":["576"],"type":"research_data","date_updated":"2025-06-12T07:34:12Z","contributor":[{"last_name":"Guet","first_name":"Calin C","contributor_type":"project_leader","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052"}],"date_published":"2019-11-13T00:00:00Z","article_processing_charge":"No","month":"11","status":"public","department":[{"_id":"CaGu"}],"date_created":"2019-11-13T09:07:31Z","publisher":"Institute of Science and Technology Austria","citation":{"apa":"Tomanek, I. (2019). Data for the paper “Gene amplification as a form of population-level gene expression regulation.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:7016","ieee":"I. Tomanek, “Data for the paper ‘Gene amplification as a form of population-level gene expression regulation.’” Institute of Science and Technology Austria, 2019.","ama":"Tomanek I. Data for the paper “Gene amplification as a form of population-level gene expression regulation.” 2019. doi:10.15479/AT:ISTA:7016","chicago":"Tomanek, Isabella. “Data for the Paper ‘Gene Amplification as a Form of Population-Level Gene Expression Regulation.’” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:7016.","ista":"Tomanek I. 2019. Data for the paper ‘Gene amplification as a form of population-level gene expression regulation’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:7016.","short":"I. Tomanek, (2019).","mla":"Tomanek, Isabella. Data for the Paper “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:7016."},"keyword":["Escherichia coli","gene amplification","galactose","DOG","experimental evolution","Illumina sequence data","FACS data","microfluidics data"],"abstract":[{"lang":"eng","text":"Organisms cope with change by employing transcriptional regulators. However, when faced with rare environments, the evolution of transcriptional regulators and their promoters may be too slow. We ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. By real-time monitoring of gene copy number mutations in E. coli, we show that gene duplications and amplifications enable adaptation to fluctuating environments by rapidly generating copy number, and hence expression level, polymorphism. This ‘amplification-mediated gene expression tuning’ occurs on timescales similar to canonical gene regulation and can deal with rapid environmental changes. Mathematical modeling shows that amplifications also tune gene expression in stochastic environments where transcription factor-based schemes are hard to evolve or maintain. The fleeting nature of gene amplifications gives rise to a generic population-level mechanism that relies on genetic heterogeneity to rapidly tune expression of any gene, without leaving any genomic signature."}],"file":[{"title":"Locus1_amplified","date_updated":"2020-07-14T12:47:47Z","file_id":"7017","content_type":"application/octet-stream","creator":"itomanek","relation":"main_file","access_level":"open_access","date_created":"2019-11-13T08:52:21Z","description":"Illumina whole genome sequence data for Locus 1 - amplified.","checksum":"72441055043eda4cbf1398a422e2c118","file_size":2456192500,"file_name":"D8_S35_R2_001.fastq"},{"checksum":"a4ac50bf655d9c751f0305ade5c2ee16","file_size":2833452234,"file_name":"IT028_S11_R2_001.fastq","date_created":"2019-11-13T08:52:59Z","description":"Illumina whole genome sequence data for Locus 1 - ancestral.","relation":"main_file","access_level":"open_access","creator":"itomanek","content_type":"application/octet-stream","file_id":"7018","date_updated":"2020-07-14T12:47:47Z","title":"Locus1_ancestral"},{"description":"Illumina whole genome sequence data for Locus 1 - 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see read_me_FACS","date_created":"2020-01-22T15:44:16Z","relation":"main_file","access_level":"open_access","checksum":"5e6745dcfb9c1b11dd935ac3ee45fe33","file_size":3765861,"file_name":"FACS_data.xlsx.zip"},{"date_created":"2020-01-22T15:44:16Z","access_level":"open_access","relation":"main_file","file_name":"read_me_FACS.rtf","file_size":4996,"checksum":"a85caf092ae4b17668f70af2d93fad00","file_id":"7352","date_updated":"2020-07-14T12:47:47Z","creator":"itomanek","content_type":"text/rtf"},{"file_name":"read_me_microfluidics.rtf","checksum":"fd8ba5d75d24e47ddf7e70bfdadb40d4","file_size":868,"date_created":"2020-01-22T15:44:16Z","access_level":"open_access","relation":"main_file","creator":"itomanek","content_type":"text/rtf","date_updated":"2020-07-14T12:47:47Z","file_id":"7353"},{"creator":"itomanek","content_type":"application/zip","file_id":"7354","date_updated":"2020-07-14T12:47:47Z","title":"microfluidics data","file_name":"microfuidics_data.zip","checksum":"69c5dc5ca5c069a138183c934acc1778","file_size":8141727,"description":"microfluidics time trace data - see read_me_microfluidics","date_created":"2020-01-22T15:44:17Z","access_level":"open_access","relation":"main_file"}],"has_accepted_license":"1","oa":1,"day":"13","year":"2019","title":"Data for the paper \"Gene amplification as a form of population-level gene expression regulation\"","doi":"10.15479/AT:ISTA:7016","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"7652"}]},"oa_version":"Published Version","file_date_updated":"2020-07-14T12:47:47Z","author":[{"full_name":"Tomanek, Isabella","orcid":"0000-0001-6197-363X","id":"3981F020-F248-11E8-B48F-1D18A9856A87","last_name":"Tomanek","first_name":"Isabella"}]},{"publisher":"Springer Nature","citation":{"ista":"Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. 2019. A modular degron library for synthetic circuits in mammalian cells. Nature Communications. 10(1), 2013.","mla":"Chassin, Hélène, et al. “A Modular Degron Library for Synthetic Circuits in Mammalian Cells.” Nature Communications, vol. 10, no. 1, 2013, Springer Nature, 2019, doi:10.1038/s41467-019-09974-5.","short":"H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, M. Fussenegger, Nature Communications 10 (2019).","chicago":"Chassin, Hélène, Marius Müller, Marcel Tigges, Leo Scheller, Moritz Lang, and Martin Fussenegger. “A Modular Degron Library for Synthetic Circuits in Mammalian Cells.” Nature Communications. Springer Nature, 2019. https://doi.org/10.1038/s41467-019-09974-5.","apa":"Chassin, H., Müller, M., Tigges, M., Scheller, L., Lang, M., & Fussenegger, M. (2019). A modular degron library for synthetic circuits in mammalian cells. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-019-09974-5","ama":"Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. A modular degron library for synthetic circuits in mammalian cells. Nature Communications. 2019;10(1). doi:10.1038/s41467-019-09974-5","ieee":"H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, and M. Fussenegger, “A modular degron library for synthetic circuits in mammalian cells,” Nature Communications, vol. 10, no. 1. Springer Nature, 2019."},"department":[{"_id":"CaGu"}],"date_created":"2019-05-19T21:59:14Z","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"status":"public","month":"05","date_published":"2019-05-01T00:00:00Z","quality_controlled":"1","intvolume":" 10","publication_identifier":{"eissn":["2041-1723"]},"issue":"1","_id":"6465","author":[{"first_name":"Hélène","last_name":"Chassin","full_name":"Chassin, Hélène"},{"full_name":"Müller, Marius","first_name":"Marius","last_name":"Müller"},{"last_name":"Tigges","first_name":"Marcel","full_name":"Tigges, Marcel"},{"full_name":"Scheller, Leo","first_name":"Leo","last_name":"Scheller"},{"first_name":"Moritz","last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz"},{"full_name":"Fussenegger, Martin","last_name":"Fussenegger","first_name":"Martin"}],"external_id":{"isi":["000466338600006"]},"isi":1,"oa_version":"Published Version","related_material":{"link":[{"url":"https://doi.org/10.1038/s41467-023-36111-0","relation":"erratum"}]},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","has_accepted_license":"1","file":[{"file_id":"6471","date_updated":"2020-07-14T12:47:31Z","creator":"dernst","content_type":"application/pdf","date_created":"2019-05-20T07:33:54Z","access_level":"open_access","relation":"main_file","file_name":"2019_NatureComm_Chassin.pdf","checksum":"e214d3e4f8c81e35981583c4569b51b8","file_size":1191827}],"article_processing_charge":"No","date_updated":"2026-04-02T11:48:53Z","type":"journal_article","publication":"Nature Communications","ddc":["570"],"scopus_import":"1","file_date_updated":"2020-07-14T12:47:31Z","publication_status":"published","doi":"10.1038/s41467-019-09974-5","title":"A modular degron library for synthetic circuits in mammalian cells","volume":10,"year":"2019","day":"01","oa":1,"abstract":[{"lang":"eng","text":"Tight control over protein degradation is a fundamental requirement for cells to respond rapidly to various stimuli and adapt to a fluctuating environment. Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons) for the precise regulation of protein expression profiles in mammalian cells by modulating target protein half-lives in a predictable manner. Using the well-established tetracycline gene-regulation system as a model, we show that the dynamics of protein expression can be tuned by fusing appropriate degron tags to gene regulators. Next, we apply this degron library to tune a synthetic pulse-generating circuit in mammalian cells. With this toolbox we establish a set of pulse generators with tailored pulse lengths and magnitudes of protein expression. This methodology will prove useful in the functional roles of essential proteins, fine-tuning of gene-expression systems, and enabling a higher complexity in the design of synthetic biological systems in mammalian cells."}],"language":[{"iso":"eng"}],"article_number":"2013"},{"publication_status":"published","doi":"10.1007/978-3-030-31304-3_9","abstract":[{"text":"The expression of a gene is characterised by its transcription factors and the function processing them. If the transcription factors are not affected by gene products, the regulating function is often represented as a combinational logic circuit, where the outputs (product) are determined by current input values (transcription factors) only, and are hence independent on their relative arrival times. However, the simultaneous arrival of transcription factors (TFs) in genetic circuits is a strong assumption, given that the processes of transcription and translation of a gene into a protein introduce intrinsic time delays and that there is no global synchronisation among the arrival times of different molecular species at molecular targets.\r\n\r\nIn this paper, we construct an experimentally implementable genetic circuit with two inputs and a single output, such that, in presence of small delays in input arrival, the circuit exhibits qualitatively distinct observable phenotypes. In particular, these phenotypes are long lived transients: they all converge to a single value, but so slowly, that they seem stable for an extended time period, longer than typical experiment duration. We used rule-based language to prototype our circuit, and we implemented a search for finding the parameter combinations raising the phenotypes of interest.\r\n\r\nThe behaviour of our prototype circuit has wide implications. First, it suggests that GRNs can exploit event timing to create phenotypes. Second, it opens the possibility that GRNs are using event timing to react to stimuli and memorise events, without explicit feedback in regulation. From the modelling perspective, our prototype circuit demonstrates the critical importance of analysing the transient dynamics at the promoter binding sites of the DNA, before applying rapid equilibrium assumptions.","lang":"eng"}],"language":[{"iso":"eng"}],"alternative_title":["LNCS"],"year":"2019","volume":11773,"title":"Transient memory in gene regulation","conference":{"start_date":"2019-09-18","location":"Trieste, Italy","end_date":"2019-09-20","name":"CMSB: Computational Methods in Systems Biology"},"day":"17","article_processing_charge":"No","scopus_import":"1","publication":"17th International Conference on Computational Methods in Systems Biology","type":"conference","date_updated":"2026-04-16T10:26:49Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","oa_version":"None","external_id":{"isi":["000557875100009"]},"author":[{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet"},{"last_name":"Henzinger","first_name":"Thomas A","orcid":"0000−0002−2985−7724","full_name":"Henzinger, Thomas A","id":"40876CD8-F248-11E8-B48F-1D18A9856A87"},{"id":"46613666-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7777-546X","full_name":"Igler, Claudia","first_name":"Claudia","last_name":"Igler"},{"last_name":"Petrov","first_name":"Tatjana","full_name":"Petrov, Tatjana","orcid":"0000-0002-9041-0905","id":"3D5811FC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sezgin","first_name":"Ali","full_name":"Sezgin, Ali","id":"4C7638DA-F248-11E8-B48F-1D18A9856A87"}],"isi":1,"page":"155-187","month":"09","status":"public","citation":{"chicago":"Guet, Calin C, Thomas A Henzinger, Claudia Igler, Tatjana Petrov, and Ali Sezgin. “Transient Memory in Gene Regulation.” In 17th International Conference on Computational Methods in Systems Biology, 11773:155–87. Springer Nature, 2019. https://doi.org/10.1007/978-3-030-31304-3_9.","ista":"Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. 2019. Transient memory in gene regulation. 17th International Conference on Computational Methods in Systems Biology. CMSB: Computational Methods in Systems Biology, LNCS, vol. 11773, 155–187.","short":"C.C. Guet, T.A. Henzinger, C. Igler, T. Petrov, A. Sezgin, in:, 17th International Conference on Computational Methods in Systems Biology, Springer Nature, 2019, pp. 155–187.","mla":"Guet, Calin C., et al. “Transient Memory in Gene Regulation.” 17th International Conference on Computational Methods in Systems Biology, vol. 11773, Springer Nature, 2019, pp. 155–87, doi:10.1007/978-3-030-31304-3_9.","ieee":"C. C. Guet, T. A. Henzinger, C. Igler, T. Petrov, and A. Sezgin, “Transient memory in gene regulation,” in 17th International Conference on Computational Methods in Systems Biology, Trieste, Italy, 2019, vol. 11773, pp. 155–187.","ama":"Guet CC, Henzinger TA, Igler C, Petrov T, Sezgin A. Transient memory in gene regulation. In: 17th International Conference on Computational Methods in Systems Biology. Vol 11773. Springer Nature; 2019:155-187. doi:10.1007/978-3-030-31304-3_9","apa":"Guet, C. C., Henzinger, T. A., Igler, C., Petrov, T., & Sezgin, A. (2019). Transient memory in gene regulation. In 17th International Conference on Computational Methods in Systems Biology (Vol. 11773, pp. 155–187). Trieste, Italy: Springer Nature. https://doi.org/10.1007/978-3-030-31304-3_9"},"publisher":"Springer Nature","date_created":"2019-12-04T16:07:50Z","department":[{"_id":"CaGu"},{"_id":"ToHe"}],"_id":"7147","intvolume":" 11773","publication_identifier":{"eissn":["1611-3349"],"issn":["0302-9743"],"eisbn":["9783030313043"],"isbn":["9783030313036"]},"date_published":"2019-09-17T00:00:00Z","project":[{"grant_number":"Z211","name":"Formal methods for the design and analysis of complex systems","_id":"25F42A32-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"grant_number":"24573","_id":"251EE76E-B435-11E9-9278-68D0E5697425","name":"Design principles underlying genetic switch architecture"}],"quality_controlled":"1"},{"article_processing_charge":"No","type":"dissertation","date_updated":"2026-04-08T13:56:27Z","degree_awarded":"PhD","ddc":["576","579"],"file_date_updated":"2021-02-11T11:17:13Z","doi":"10.15479/AT:ISTA:6371","publication_status":"published","oa":1,"day":"03","alternative_title":["ISTA Thesis"],"year":"2019","title":"On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation","language":[{"iso":"eng"}],"corr_author":"1","abstract":[{"lang":"eng","text":"Decades of studies have revealed the mechanisms of gene regulation in molecular detail. We make use of such well-described regulatory systems to explore how the molecular mechanisms of protein-protein and protein-DNA interactions shape the dynamics and evolution of gene regulation. \r\n\r\ni) We uncover how the biophysics of protein-DNA binding determines the potential of regulatory networks to evolve and adapt, which can be captured using a simple mathematical model. \r\nii) The evolution of regulatory connections can lead to a significant amount of crosstalk between binding proteins. We explore the effect of crosstalk on gene expression from a target promoter, which seems to be modulated through binding competition at non-specific DNA sites. \r\niii) We investigate how the very same biophysical characteristics as in i) can generate significant fitness costs for cells through global crosstalk, meaning non-specific DNA binding across the genomic background. \r\niv) Binding competition between proteins at a target promoter is a prevailing regulatory feature due to the prevalence of co-regulation at bacterial promoters. However, the dynamics of these systems are not always straightforward to determine even if the molecular mechanisms of regulation are known. A detailed model of the biophysical interactions reveals that interference between the regulatory proteins can constitute a new, generic form of system memory that records the history of the input signals at the promoter. \r\n\r\nWe demonstrate how the biophysics of protein-DNA binding can be harnessed to investigate the principles that shape and ultimately limit cellular gene regulation. These results provide a basis for studies of higher-level functionality, which arises from the underlying regulation. \r\n"}],"supervisor":[{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C"}],"department":[{"_id":"CaGu"}],"date_created":"2019-05-03T11:55:51Z","publisher":"Institute of Science and Technology Austria","citation":{"ieee":"C. Igler, “On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation,” Institute of Science and Technology Austria, 2019.","ama":"Igler C. On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. 2019. doi:10.15479/AT:ISTA:6371","apa":"Igler, C. (2019). On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6371","ista":"Igler C. 2019. On the nature of gene regulatory design - The biophysics of transcription factor binding shapes gene regulation. Institute of Science and Technology Austria.","mla":"Igler, Claudia. On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6371.","short":"C. Igler, On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation, Institute of Science and Technology Austria, 2019.","chicago":"Igler, Claudia. “On the Nature of Gene Regulatory Design - The Biophysics of Transcription Factor Binding Shapes Gene Regulation.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6371."},"month":"05","status":"public","page":"152","project":[{"grant_number":"24573","name":"Design principles underlying genetic switch architecture","_id":"251EE76E-B435-11E9-9278-68D0E5697425"}],"date_published":"2019-05-03T00:00:00Z","_id":"6371","publication_identifier":{"issn":["2663-337X"]},"OA_place":"publisher","author":[{"orcid":"0000-0001-7777-546X","full_name":"Igler, Claudia","id":"46613666-F248-11E8-B48F-1D18A9856A87","last_name":"Igler","first_name":"Claudia"}],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","oa_version":"Published Version","related_material":{"record":[{"id":"67","status":"public","relation":"part_of_dissertation"},{"status":"public","id":"5585","relation":"popular_science"}]},"keyword":["gene regulation","biophysics","transcription factor binding","bacteria"],"file":[{"content_type":"application/pdf","creator":"cigler","date_updated":"2021-02-11T11:17:13Z","file_id":"6373","checksum":"c0085d47c58c9cbcab1b0a783480f6da","file_size":12597663,"file_name":"IglerClaudia_OntheNatureofGeneRegulatoryDesign.pdf","embargo":"2020-05-02","relation":"main_file","access_level":"open_access","date_created":"2019-05-03T11:54:52Z"},{"file_id":"6374","date_updated":"2020-07-14T12:47:28Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","creator":"cigler","access_level":"closed","relation":"source_file","date_created":"2019-05-03T11:54:54Z","embargo_to":"open_access","file_name":"IglerClaudia_OntheNatureofGeneRegulatoryDesign.docx","checksum":"2eac954de1c8bbf7e6fb35ed0221ae8c","file_size":34644426}],"has_accepted_license":"1"},{"scopus_import":1,"date_updated":"2021-01-12T07:40:42Z","type":"journal_article","publication":"Methods in Molecular Biology","language":[{"iso":"eng"}],"publist_id":"7574","abstract":[{"text":"The hanging-drop network (HDN) is a technology platform based on a completely open microfluidic network at the bottom of an inverted, surface-patterned substrate. The platform is predominantly used for the formation, culturing, and interaction of self-assembled spherical microtissues (spheroids) under precisely controlled flow conditions. Here, we describe design, fabrication, and operation of microfluidic hanging-drop networks.","lang":"eng"}],"day":"01","title":"Fabrication and operation of microfluidic hanging drop networks","volume":1771,"year":"2018","alternative_title":["MIMB"],"doi":"10.1007/978-1-4939-7792-5_15","publication_status":"published","ec_funded":1,"intvolume":" 1771","_id":"305","project":[{"call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734"}],"quality_controlled":"1","date_published":"2018-01-01T00:00:00Z","status":"public","month":"01","page":"183 - 202","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"date_created":"2018-12-11T11:45:43Z","publisher":"Springer","citation":{"chicago":"Misun, Patrick, Axel Birchler, Moritz Lang, Andreas Hierlemann, and Olivier Frey. “Fabrication and Operation of Microfluidic Hanging Drop Networks.” Methods in Molecular Biology. Springer, 2018. https://doi.org/10.1007/978-1-4939-7792-5_15.","short":"P. Misun, A. Birchler, M. Lang, A. Hierlemann, O. Frey, Methods in Molecular Biology 1771 (2018) 183–202.","mla":"Misun, Patrick, et al. “Fabrication and Operation of Microfluidic Hanging Drop Networks.” Methods in Molecular Biology, vol. 1771, Springer, 2018, pp. 183–202, doi:10.1007/978-1-4939-7792-5_15.","ista":"Misun P, Birchler A, Lang M, Hierlemann A, Frey O. 2018. Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. 1771, 183–202.","ieee":"P. Misun, A. Birchler, M. Lang, A. Hierlemann, and O. Frey, “Fabrication and operation of microfluidic hanging drop networks,” Methods in Molecular Biology, vol. 1771. Springer, pp. 183–202, 2018.","apa":"Misun, P., Birchler, A., Lang, M., Hierlemann, A., & Frey, O. (2018). Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. Springer. https://doi.org/10.1007/978-1-4939-7792-5_15","ama":"Misun P, Birchler A, Lang M, Hierlemann A, Frey O. Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. 2018;1771:183-202. doi:10.1007/978-1-4939-7792-5_15"},"acknowledgement":"This work was financially supported by FP7 of the EU through the project “Body on a chip,” ICT-FET-296257, and the ERC Advanced Grant “NeuroCMOS” (contract 267351), as well as by an individual Ambizione Grant 142440 from the Swiss National Science Foundation for Olivier Frey. The research leading to these results also received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. [291734]. We would like to thank Alexander Stettler, ETH Zurich for his expertise and support in the cleanroom, and we acknowledge the Single Cell Unit of D-BSSE, ETH Zurich for assistance in microscopy issues. M.L. is grateful to the members of the Guet and Tkačik groups, IST Austria, for valuable comments and support.","oa_version":"None","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Misun","first_name":"Patrick","full_name":"Misun, Patrick"},{"first_name":"Axel","last_name":"Birchler","full_name":"Birchler, Axel"},{"first_name":"Moritz","last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz"},{"last_name":"Hierlemann","first_name":"Andreas","full_name":"Hierlemann, Andreas"},{"first_name":"Olivier","last_name":"Frey","full_name":"Frey, Olivier"}]},{"year":"2018","volume":35,"title":"Nonoptimal gene expression creates latent potential for antibiotic resistance","oa":1,"day":"28","abstract":[{"text":"Bacteria regulate genes to survive antibiotic stress, but regulation can be far from perfect. When regulation is not optimal, mutations that change gene expression can contribute to antibiotic resistance. It is not systematically understood to what extent natural gene regulation is or is not optimal for distinct antibiotics, and how changes in expression of specific genes quantitatively affect antibiotic resistance. Here we discover a simple quantitative relation between fitness, gene expression, and antibiotic potency, which rationalizes our observation that a multitude of genes and even innate antibiotic defense mechanisms have expression that is critically nonoptimal under antibiotic treatment. First, we developed a pooled-strain drug-diffusion assay and screened Escherichia coli overexpression and knockout libraries, finding that resistance to a range of 31 antibiotics could result from changing expression of a large and functionally diverse set of genes, in a primarily but not exclusively drug-specific manner. Second, by synthetically controlling the expression of single-drug and multidrug resistance genes, we observed that their fitness-expression functions changed dramatically under antibiotic treatment in accordance with a log-sensitivity relation. Thus, because many genes are nonoptimally expressed under antibiotic treatment, many regulatory mutations can contribute to resistance by altering expression and by activating latent defenses.","lang":"eng"}],"publist_id":"8036","language":[{"iso":"eng"}],"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pubmed/30169679","open_access":"1"}],"publication_status":"published","doi":"10.1093/molbev/msy163","type":"journal_article","publication":"Molecular Biology and Evolution","date_updated":"2023-10-17T11:51:06Z","scopus_import":"1","article_type":"original","article_processing_charge":"No","external_id":{"pmid":["30169679"],"isi":["000452567200006"]},"pmid":1,"author":[{"last_name":"Palmer","first_name":"Adam","full_name":"Palmer, Adam"},{"id":"3464AE84-F248-11E8-B48F-1D18A9856A87","full_name":"Chait, Remy P","orcid":"0000-0003-0876-3187","first_name":"Remy P","last_name":"Chait"},{"full_name":"Kishony, Roy","last_name":"Kishony","first_name":"Roy"}],"isi":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Submitted Version","date_published":"2018-08-28T00:00:00Z","quality_controlled":"1","_id":"19","intvolume":" 35","issue":"11","publication_identifier":{"issn":["0737-4038"]},"publisher":"Oxford University Press","citation":{"apa":"Palmer, A., Chait, R. P., & Kishony, R. (2018). Nonoptimal gene expression creates latent potential for antibiotic resistance. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msy163","ieee":"A. Palmer, R. P. Chait, and R. Kishony, “Nonoptimal gene expression creates latent potential for antibiotic resistance,” Molecular Biology and Evolution, vol. 35, no. 11. Oxford University Press, pp. 2669–2684, 2018.","ama":"Palmer A, Chait RP, Kishony R. Nonoptimal gene expression creates latent potential for antibiotic resistance. Molecular Biology and Evolution. 2018;35(11):2669-2684. doi:10.1093/molbev/msy163","short":"A. Palmer, R.P. Chait, R. Kishony, Molecular Biology and Evolution 35 (2018) 2669–2684.","mla":"Palmer, Adam, et al. “Nonoptimal Gene Expression Creates Latent Potential for Antibiotic Resistance.” Molecular Biology and Evolution, vol. 35, no. 11, Oxford University Press, 2018, pp. 2669–84, doi:10.1093/molbev/msy163.","ista":"Palmer A, Chait RP, Kishony R. 2018. Nonoptimal gene expression creates latent potential for antibiotic resistance. Molecular Biology and Evolution. 35(11), 2669–2684.","chicago":"Palmer, Adam, Remy P Chait, and Roy Kishony. “Nonoptimal Gene Expression Creates Latent Potential for Antibiotic Resistance.” Molecular Biology and Evolution. Oxford University Press, 2018. https://doi.org/10.1093/molbev/msy163."},"department":[{"_id":"CaGu"},{"_id":"GaTk"}],"date_created":"2018-12-11T11:44:11Z","page":"2669 - 2684","month":"08","status":"public"},{"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","related_material":{"record":[{"id":"5587","status":"public","relation":"popular_science"}]},"oa_version":"Published Version","external_id":{"isi":["000440149300021"]},"author":[{"last_name":"De Martino","first_name":"Daniele","id":"3FF5848A-F248-11E8-B48F-1D18A9856A87","full_name":"De Martino, Daniele","orcid":"0000-0002-5214-4706"},{"first_name":"Andersson Anna","last_name":"Mc","full_name":"Mc, Andersson Anna"},{"id":"2C471CFA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5396-4346","full_name":"Bergmiller, Tobias","last_name":"Bergmiller","first_name":"Tobias"},{"full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkacik, Gasper","orcid":"0000-0002-6699-1455","last_name":"Tkacik","first_name":"Gasper"}],"isi":1,"file":[{"checksum":"3ba7ab27b27723c7dcf633e8fc1f8f18","file_size":1043205,"file_name":"2018_NatureComm_DeMartino.pdf","date_created":"2018-12-17T16:44:28Z","relation":"main_file","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_id":"5728","date_updated":"2020-07-14T12:45:06Z"}],"has_accepted_license":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"month":"07","status":"public","citation":{"mla":"De Martino, Daniele, et al. “Statistical Mechanics for Metabolic Networks during Steady State Growth.” Nature Communications, vol. 9, no. 1, 2988, Springer Nature, 2018, doi:10.1038/s41467-018-05417-9.","short":"D. De Martino, A.A. Mc, T. Bergmiller, C.C. Guet, G. Tkačik, Nature Communications 9 (2018).","ista":"De Martino D, Mc AA, Bergmiller T, Guet CC, Tkačik G. 2018. Statistical mechanics for metabolic networks during steady state growth. Nature Communications. 9(1), 2988.","chicago":"De Martino, Daniele, Andersson Anna Mc, Tobias Bergmiller, Calin C Guet, and Gašper Tkačik. “Statistical Mechanics for Metabolic Networks during Steady State Growth.” Nature Communications. Springer Nature, 2018. https://doi.org/10.1038/s41467-018-05417-9.","ama":"De Martino D, Mc AA, Bergmiller T, Guet CC, Tkačik G. Statistical mechanics for metabolic networks during steady state growth. Nature Communications. 2018;9(1). doi:10.1038/s41467-018-05417-9","ieee":"D. De Martino, A. A. Mc, T. Bergmiller, C. C. Guet, and G. Tkačik, “Statistical mechanics for metabolic networks during steady state growth,” Nature Communications, vol. 9, no. 1. Springer Nature, 2018.","apa":"De Martino, D., Mc, A. A., Bergmiller, T., Guet, C. C., & Tkačik, G. (2018). Statistical mechanics for metabolic networks during steady state growth. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-018-05417-9"},"publisher":"Springer Nature","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"date_created":"2018-12-11T11:44:57Z","_id":"161","issue":"1","intvolume":" 9","date_published":"2018-07-30T00:00:00Z","project":[{"_id":"254E9036-B435-11E9-9278-68D0E5697425","name":"Biophysics of information processing in gene regulation","call_identifier":"FWF","grant_number":"P28844-B27"},{"_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme","call_identifier":"FP7","grant_number":"291734"}],"quality_controlled":"1","publication_status":"published","doi":"10.1038/s41467-018-05417-9","ec_funded":1,"file_date_updated":"2020-07-14T12:45:06Z","abstract":[{"text":"Which properties of metabolic networks can be derived solely from stoichiometry? Predictive results have been obtained by flux balance analysis (FBA), by postulating that cells set metabolic fluxes to maximize growth rate. Here we consider a generalization of FBA to single-cell level using maximum entropy modeling, which we extend and test experimentally. Specifically, we define for Escherichia coli metabolism a flux distribution that yields the experimental growth rate: the model, containing FBA as a limit, provides a better match to measured fluxes and it makes a wide range of predictions: on flux variability, regulation, and correlations; on the relative importance of stoichiometry vs. optimization; on scaling relations for growth rate distributions. We validate the latter here with single-cell data at different sub-inhibitory antibiotic concentrations. The model quantifies growth optimization as emerging from the interplay of competitive dynamics in the population and regulation of metabolism at the level of single cells.","lang":"eng"}],"publist_id":"7760","article_number":"2988","language":[{"iso":"eng"}],"year":"2018","volume":9,"title":"Statistical mechanics for metabolic networks during steady state growth","oa":1,"day":"30","article_processing_charge":"No","scopus_import":"1","ddc":["570"],"publication":"Nature Communications","type":"journal_article","date_updated":"2025-04-15T06:50:08Z"},{"abstract":[{"text":"In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage, bacterial cells resistant to the phage commonly emerge and become the dominant population of bacteria. Following the ascent of resistant mutants, the densities of bacteria in these simple communities become limited by resources rather than the phage. Despite the evolution of resistant hosts, upon which the phage cannot replicate, the lytic phage population is most commonly maintained in an apparently stable state with the resistant bacteria. Several mechanisms have been put forward to account for this result. Here we report the results of population dynamic/evolution experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli in serial transfer cultures. We show that, following the ascent of λVIR-resistant bacteria, λVIRis maintained in the majority of cases in maltose-limited minimal media and in all cases in nutrient-rich broth. Using mathematical models and experiments, we show that the dominant mechanism responsible for maintenance of λVIRin these resource-limited populations dominated by resistant E. coli is a high rate of either phenotypic or genetic transition from resistance to susceptibility—a hitherto undemonstrated mechanism we term "leaky resistance." We discuss the implications of leaky resistance to our understanding of the conditions for the maintenance of phage in populations of bacteria—their “existence conditions.”.","lang":"eng"}],"language":[{"iso":"eng"}],"article_number":"2005971","publist_id":"7972","title":"Leaky resistance and the conditions for the existence of lytic bacteriophage","volume":16,"year":"2018","day":"16","oa":1,"publication_status":"published","doi":"10.1371/journal.pbio.2005971","file_date_updated":"2020-07-14T12:48:10Z","ddc":["570"],"scopus_import":"1","date_updated":"2023-09-13T08:45:41Z","type":"journal_article","publication":"PLoS Biology","article_processing_charge":"Yes","has_accepted_license":"1","file":[{"file_name":"2018_Plos_Chaudhry.pdf","checksum":"527076f78265cd4ea192cd1569851587","file_size":4007095,"date_created":"2018-12-17T12:55:31Z","access_level":"open_access","relation":"main_file","creator":"dernst","content_type":"application/pdf","file_id":"5706","date_updated":"2020-07-14T12:48:10Z"}],"oa_version":"Published Version","related_material":{"record":[{"status":"public","id":"9810","relation":"research_data"}]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","author":[{"first_name":"Waqas","last_name":"Chaudhry","full_name":"Chaudhry, Waqas"},{"full_name":"Pleska, Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479","last_name":"Pleska","first_name":"Maros"},{"full_name":"Shah, Nilang","last_name":"Shah","first_name":"Nilang"},{"full_name":"Weiss, Howard","first_name":"Howard","last_name":"Weiss"},{"last_name":"Mccall","first_name":"Ingrid","full_name":"Mccall, Ingrid"},{"last_name":"Meyer","first_name":"Justin","full_name":"Meyer, Justin"},{"full_name":"Gupta, Animesh","last_name":"Gupta","first_name":"Animesh"},{"last_name":"Guet","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C"},{"full_name":"Levin, Bruce","first_name":"Bruce","last_name":"Levin"}],"external_id":{"isi":["000443383300024"]},"isi":1,"intvolume":" 16","issue":"8","_id":"82","date_published":"2018-08-16T00:00:00Z","quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)"},"status":"public","month":"08","publisher":"Public Library of Science","citation":{"apa":"Chaudhry, W., Pleska, M., Shah, N., Weiss, H., Mccall, I., Meyer, J., … Levin, B. (2018). Leaky resistance and the conditions for the existence of lytic bacteriophage. PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.2005971","ieee":"W. Chaudhry et al., “Leaky resistance and the conditions for the existence of lytic bacteriophage,” PLoS Biology, vol. 16, no. 8. Public Library of Science, 2018.","ama":"Chaudhry W, Pleska M, Shah N, et al. Leaky resistance and the conditions for the existence of lytic bacteriophage. PLoS Biology. 2018;16(8). doi:10.1371/journal.pbio.2005971","ista":"Chaudhry W, Pleska M, Shah N, Weiss H, Mccall I, Meyer J, Gupta A, Guet CC, Levin B. 2018. Leaky resistance and the conditions for the existence of lytic bacteriophage. PLoS Biology. 16(8), 2005971.","mla":"Chaudhry, Waqas, et al. “Leaky Resistance and the Conditions for the Existence of Lytic Bacteriophage.” PLoS Biology, vol. 16, no. 8, 2005971, Public Library of Science, 2018, doi:10.1371/journal.pbio.2005971.","short":"W. Chaudhry, M. Pleska, N. Shah, H. Weiss, I. Mccall, J. Meyer, A. Gupta, C.C. Guet, B. Levin, PLoS Biology 16 (2018).","chicago":"Chaudhry, Waqas, Maros Pleska, Nilang Shah, Howard Weiss, Ingrid Mccall, Justin Meyer, Animesh Gupta, Calin C Guet, and Bruce Levin. “Leaky Resistance and the Conditions for the Existence of Lytic Bacteriophage.” PLoS Biology. Public Library of Science, 2018. https://doi.org/10.1371/journal.pbio.2005971."},"date_created":"2018-12-11T11:44:32Z","department":[{"_id":"CaGu"}]},{"author":[{"last_name":"Chaudhry","first_name":"Waqas","full_name":"Chaudhry, Waqas"},{"last_name":"Pleska","first_name":"Maros","orcid":"0000-0001-7460-7479","full_name":"Pleska, Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Nilang","last_name":"Shah","full_name":"Shah, Nilang"},{"full_name":"Weiss, Howard","first_name":"Howard","last_name":"Weiss"},{"full_name":"Mccall, Ingrid","last_name":"Mccall","first_name":"Ingrid"},{"full_name":"Meyer, Justin","last_name":"Meyer","first_name":"Justin"},{"full_name":"Gupta, Animesh","last_name":"Gupta","first_name":"Animesh"},{"orcid":"0000-0001-6220-2052","full_name":"Guet, Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","last_name":"Guet"},{"full_name":"Levin, Bruce","last_name":"Levin","first_name":"Bruce"}],"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","doi":"10.1371/journal.pbio.2005971.s008","oa_version":"Published Version","related_material":{"record":[{"status":"public","id":"82","relation":"used_in_publication"}]},"year":"2018","title":"Numerical data used in figures","day":"16","publisher":"Public Library of Science","citation":{"chicago":"Chaudhry, Waqas, Maros Pleska, Nilang Shah, Howard Weiss, Ingrid Mccall, Justin Meyer, Animesh Gupta, Calin C Guet, and Bruce Levin. “Numerical Data Used in Figures.” Public Library of Science, 2018. https://doi.org/10.1371/journal.pbio.2005971.s008.","short":"W. Chaudhry, M. Pleska, N. Shah, H. Weiss, I. Mccall, J. Meyer, A. Gupta, C.C. Guet, B. Levin, (2018).","mla":"Chaudhry, Waqas, et al. Numerical Data Used in Figures. Public Library of Science, 2018, doi:10.1371/journal.pbio.2005971.s008.","ista":"Chaudhry W, Pleska M, Shah N, Weiss H, Mccall I, Meyer J, Gupta A, Guet CC, Levin B. 2018. Numerical data used in figures, Public Library of Science, 10.1371/journal.pbio.2005971.s008.","ieee":"W. Chaudhry et al., “Numerical data used in figures.” Public Library of Science, 2018.","apa":"Chaudhry, W., Pleska, M., Shah, N., Weiss, H., Mccall, I., Meyer, J., … Levin, B. (2018). Numerical data used in figures. Public Library of Science. https://doi.org/10.1371/journal.pbio.2005971.s008","ama":"Chaudhry W, Pleska M, Shah N, et al. Numerical data used in figures. 2018. doi:10.1371/journal.pbio.2005971.s008"},"department":[{"_id":"CaGu"}],"date_created":"2021-08-06T12:43:44Z","article_processing_charge":"No","month":"08","status":"public","date_published":"2018-08-16T00:00:00Z","type":"research_data_reference","date_updated":"2023-09-13T08:45:41Z","_id":"9810"},{"article_processing_charge":"No","scopus_import":"1","type":"journal_article","publication":"Journal of Biotechnology","date_updated":"2024-10-09T20:58:29Z","publication_status":"published","doi":"10.1016/j.jbiotec.2018.01.008","abstract":[{"text":"Buffers are essential for diluting bacterial cultures for flow cytometry analysis in order to study bacterial physiology and gene expression parameters based on fluorescence signals. Using a variety of constitutively expressed fluorescent proteins in Escherichia coli K-12 strain MG1655, we found strong artifactual changes in fluorescence levels after dilution into the commonly used flow cytometry buffer phosphate-buffered saline (PBS) and two other buffer solutions, Tris-HCl and M9 salts. These changes appeared very rapidly after dilution, and were linked to increased membrane permeability and loss in cell viability. We observed buffer-related effects in several different E. coli strains, K-12, C and W, but not E. coli B, which can be partially explained by differences in lipopolysaccharide (LPS) and outer membrane composition. Supplementing the buffers with divalent cations responsible for outer membrane stability, Mg2+ and Ca2+, preserved fluorescence signals, membrane integrity and viability of E. coli. Thus, stabilizing the bacterial outer membrane is essential for precise and unbiased measurements of fluorescence parameters using flow cytometry.","lang":"eng"}],"corr_author":"1","acknowledged_ssus":[{"_id":"Bio"}],"publist_id":"7317","language":[{"iso":"eng"}],"year":"2018","title":"Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains","volume":268,"day":"20","page":"40 - 52","month":"02","status":"public","publisher":"Elsevier","citation":{"chicago":"Tomasek, Kathrin, Tobias Bergmiller, and Calin C Guet. “Lack of Cations in Flow Cytometry Buffers Affect Fluorescence Signals by Reducing Membrane Stability and Viability of Escherichia Coli Strains.” Journal of Biotechnology. Elsevier, 2018. https://doi.org/10.1016/j.jbiotec.2018.01.008.","ista":"Tomasek K, Bergmiller T, Guet CC. 2018. Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains. Journal of Biotechnology. 268, 40–52.","short":"K. Tomasek, T. Bergmiller, C.C. Guet, Journal of Biotechnology 268 (2018) 40–52.","mla":"Tomasek, Kathrin, et al. “Lack of Cations in Flow Cytometry Buffers Affect Fluorescence Signals by Reducing Membrane Stability and Viability of Escherichia Coli Strains.” Journal of Biotechnology, vol. 268, Elsevier, 2018, pp. 40–52, doi:10.1016/j.jbiotec.2018.01.008.","ama":"Tomasek K, Bergmiller T, Guet CC. Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains. Journal of Biotechnology. 2018;268:40-52. doi:10.1016/j.jbiotec.2018.01.008","ieee":"K. Tomasek, T. Bergmiller, and C. C. Guet, “Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains,” Journal of Biotechnology, vol. 268. Elsevier, pp. 40–52, 2018.","apa":"Tomasek, K., Bergmiller, T., & Guet, C. C. (2018). Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains. Journal of Biotechnology. Elsevier. https://doi.org/10.1016/j.jbiotec.2018.01.008"},"department":[{"_id":"CaGu"}],"date_created":"2018-12-11T11:46:50Z","_id":"503","intvolume":" 268","date_published":"2018-02-20T00:00:00Z","quality_controlled":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"None","external_id":{"isi":["000425715100006"]},"author":[{"last_name":"Tomasek","first_name":"Kathrin","orcid":"0000-0003-3768-877X","full_name":"Tomasek, Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Tobias","last_name":"Bergmiller","full_name":"Bergmiller, Tobias","orcid":"0000-0001-5396-4346","id":"2C471CFA-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C"}],"isi":1,"acknowledgement":"We thank R Chait and M Lagator for sharing Bacillus subtilis CR_Y1 and pZS*_2R-cIPtet-Venus-Prm, respectively. We are grateful to T Pilizota and all members of the Guet lab for critically reading the manuscript. We also thank the Bioimaging facility at IST Austria for assistance using the FACSAria III system.\r\n\r\n"}]