[{"article_number":"e52067","citation":{"short":"M. Narasimhan, A.J. Johnson, R. Prizak, W. Kaufmann, S. Tan, B.E. Casillas Perez, J. Friml, ELife 9 (2020).","chicago":"Narasimhan, Madhumitha, Alexander J Johnson, Roshan Prizak, Walter Kaufmann, Shutang Tan, Barbara E Casillas Perez, and Jiří Friml. “Evolutionarily Unique Mechanistic Framework of Clathrin-Mediated Endocytosis in Plants.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/eLife.52067\">https://doi.org/10.7554/eLife.52067</a>.","ista":"Narasimhan M, Johnson AJ, Prizak R, Kaufmann W, Tan S, Casillas Perez BE, Friml J. 2020. Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. eLife. 9, e52067.","mla":"Narasimhan, Madhumitha, et al. “Evolutionarily Unique Mechanistic Framework of Clathrin-Mediated Endocytosis in Plants.” <i>ELife</i>, vol. 9, e52067, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/eLife.52067\">10.7554/eLife.52067</a>.","ama":"Narasimhan M, Johnson AJ, Prizak R, et al. Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/eLife.52067\">10.7554/eLife.52067</a>","ieee":"M. Narasimhan <i>et al.</i>, “Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020.","apa":"Narasimhan, M., Johnson, A. J., Prizak, R., Kaufmann, W., Tan, S., Casillas Perez, B. E., &#38; Friml, J. (2020). Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.52067\">https://doi.org/10.7554/eLife.52067</a>"},"ddc":["570","580"],"status":"public","publication":"eLife","publisher":"eLife Sciences Publications","file":[{"date_updated":"2020-07-14T12:47:59Z","access_level":"open_access","date_created":"2020-02-18T07:21:16Z","checksum":"2052daa4be5019534f3a42f200a09f32","file_size":7247468,"content_type":"application/pdf","file_name":"2020_eLife_Narasimhan.pdf","creator":"dernst","file_id":"7494","relation":"main_file"}],"has_accepted_license":"1","scopus_import":"1","ec_funded":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"EM-Fac"}],"date_updated":"2025-04-14T07:45:03Z","author":[{"full_name":"Narasimhan, Madhumitha","last_name":"Narasimhan","first_name":"Madhumitha","id":"44BF24D0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8600-0671"},{"id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2739-8843","first_name":"Alexander J","last_name":"Johnson","full_name":"Johnson, Alexander J"},{"last_name":"Prizak","first_name":"Roshan","full_name":"Prizak, Roshan","id":"4456104E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kaufmann, Walter","first_name":"Walter","last_name":"Kaufmann","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315"},{"id":"2DE75584-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0471-8285","last_name":"Tan","first_name":"Shutang","full_name":"Tan, Shutang"},{"id":"351ED2AA-F248-11E8-B48F-1D18A9856A87","full_name":"Casillas Perez, Barbara E","first_name":"Barbara E","last_name":"Casillas Perez"},{"id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596","full_name":"Friml, Jiří","last_name":"Friml","first_name":"Jiří"}],"year":"2020","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"article_type":"original","quality_controlled":"1","volume":9,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","day":"23","pmid":1,"intvolume":"         9","publication_status":"published","language":[{"iso":"eng"}],"date_published":"2020-01-23T00:00:00Z","isi":1,"_id":"7490","publication_identifier":{"eissn":["2050-084X"]},"external_id":{"pmid":["31971511"],"isi":["000514104100001"]},"project":[{"_id":"261099A6-B435-11E9-9278-68D0E5697425","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","grant_number":"742985","call_identifier":"H2020"},{"_id":"26538374-B435-11E9-9278-68D0E5697425","grant_number":"I03630","name":"Molecular mechanisms of endocytic cargo recognition in plants","call_identifier":"FWF"}],"type":"journal_article","file_date_updated":"2020-07-14T12:47:59Z","month":"01","abstract":[{"lang":"eng","text":"In plants, clathrin mediated endocytosis (CME) represents the major route for cargo internalisation from the cell surface. It has been assumed to operate in an evolutionary conserved manner as in yeast and animals. Here we report characterisation of ultrastructure, dynamics and mechanisms of plant CME as allowed by our advancement in electron microscopy and quantitative live imaging techniques. Arabidopsis CME appears to follow the constant curvature model and the bona fide CME population generates vesicles of a predominantly hexagonal-basket type; larger and with faster kinetics than in other models. Contrary to the existing paradigm, actin is dispensable for CME events at the plasma membrane but plays a unique role in collecting endocytic vesicles, sorting of internalised cargos and directional endosome movement that itself actively promote CME events. Internalized vesicles display a strongly delayed and sequential uncoating. These unique features highlight the independent evolution of the plant CME mechanism during the autonomous rise of multicellularity in eukaryotes."}],"license":"https://creativecommons.org/licenses/by/4.0/","oa_version":"Published Version","date_created":"2020-02-16T23:00:50Z","doi":"10.7554/eLife.52067","article_processing_charge":"No","title":"Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants","department":[{"_id":"JiFr"},{"_id":"GaTk"},{"_id":"EM-Fac"},{"_id":"SyCr"}]},{"date_published":"2020-02-25T00:00:00Z","related_material":{"record":[{"status":"deleted","id":"9716","relation":"research_data"},{"relation":"research_data","id":"9776","status":"public"},{"status":"public","id":"9779","relation":"research_data"},{"id":"9777","relation":"research_data","status":"public"},{"status":"public","id":"8155","relation":"dissertation_contains"}]},"_id":"7569","isi":1,"pmid":1,"intvolume":"        16","publication_status":"published","language":[{"iso":"eng"}],"date_created":"2020-03-06T07:39:38Z","doi":"10.1371/journal.pcbi.1007642","oa_version":"Published Version","article_processing_charge":"No","title":"The relation between crosstalk and gene regulation form revisited","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"publication_identifier":{"issn":["1553-7358"]},"external_id":{"isi":["000526725200019"],"pmid":["32097416"]},"type":"journal_article","month":"02","file_date_updated":"2020-07-14T12:48:00Z","abstract":[{"text":"Genes differ in the frequency at which they are expressed and in the form of regulation used to control their activity. In particular, positive or negative regulation can lead to activation of a gene in response to an external signal. Previous works proposed that the form of regulation of a gene correlates with its frequency of usage: positive regulation when the gene is frequently expressed and negative regulation when infrequently expressed. Such network design means that, in the absence of their regulators, the genes are found in their least required activity state, hence regulatory intervention is often necessary. Due to the multitude of genes and regulators, spurious binding and unbinding events, called “crosstalk”, could occur. To determine how the form of regulation affects the global crosstalk in the network, we used a mathematical model that includes multiple regulators and multiple target genes. We found that crosstalk depends non-monotonically on the availability of regulators. Our analysis showed that excess use of regulation entailed by the formerly suggested network design caused high crosstalk levels in a large part of the parameter space. We therefore considered the opposite ‘idle’ design, where the default unregulated state of genes is their frequently required activity state. We found, that ‘idle’ design minimized the use of regulation and thus minimized crosstalk. In addition, we estimated global crosstalk of S. cerevisiae using transcription factors binding data. We demonstrated that even partial network data could suffice to estimate its global crosstalk, suggesting its applicability to additional organisms. We found that S. cerevisiae estimated crosstalk is lower than that of a random network, suggesting that natural selection reduces crosstalk. In summary, our study highlights a new type of protein production cost which is typically overlooked: that of regulatory interference caused by the presence of excess regulators in the cell. It demonstrates the importance of whole-network descriptions, which could show effects missed by single-gene models.","lang":"eng"}],"date_updated":"2026-04-08T07:25:08Z","author":[{"orcid":"0000-0003-2539-3560","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","full_name":"Grah, Rok","first_name":"Rok","last_name":"Grah"},{"full_name":"Friedlander, Tamar","last_name":"Friedlander","first_name":"Tamar"}],"year":"2020","citation":{"chicago":"Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene Regulation Form Revisited.” <i>PLOS Computational Biology</i>. Public Library of Science, 2020. <a href=\"https://doi.org/10.1371/journal.pcbi.1007642\">https://doi.org/10.1371/journal.pcbi.1007642</a>.","ista":"Grah R, Friedlander T. 2020. The relation between crosstalk and gene regulation form revisited. PLOS Computational Biology. 16(2), e1007642.","short":"R. Grah, T. Friedlander, PLOS Computational Biology 16 (2020).","mla":"Grah, Rok, and Tamar Friedlander. “The Relation between Crosstalk and Gene Regulation Form Revisited.” <i>PLOS Computational Biology</i>, vol. 16, no. 2, e1007642, Public Library of Science, 2020, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007642\">10.1371/journal.pcbi.1007642</a>.","ieee":"R. Grah and T. Friedlander, “The relation between crosstalk and gene regulation form revisited,” <i>PLOS Computational Biology</i>, vol. 16, no. 2. Public Library of Science, 2020.","apa":"Grah, R., &#38; Friedlander, T. (2020). The relation between crosstalk and gene regulation form revisited. <i>PLOS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1007642\">https://doi.org/10.1371/journal.pcbi.1007642</a>","ama":"Grah R, Friedlander T. The relation between crosstalk and gene regulation form revisited. <i>PLOS Computational Biology</i>. 2020;16(2). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007642\">10.1371/journal.pcbi.1007642</a>"},"article_number":"e1007642","ddc":["000","570"],"publication":"PLOS Computational Biology","status":"public","publisher":"Public Library of Science","file":[{"file_name":"2020_PlosCompBio_Grah.pdf","creator":"dernst","file_id":"7579","relation":"main_file","file_size":2209325,"checksum":"5239dd134dc6e1c71fe7b3ce2953da37","content_type":"application/pdf","access_level":"open_access","date_updated":"2020-07-14T12:48:00Z","date_created":"2020-03-09T15:12:21Z"}],"scopus_import":"1","has_accepted_license":"1","issue":"2","volume":16,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"25","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"article_type":"original","quality_controlled":"1"},{"author":[{"orcid":"0000-0003-2539-3560","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","first_name":"Rok","last_name":"Grah","full_name":"Grah, Rok"}],"year":"2020","date_updated":"2026-04-08T07:25:09Z","publisher":"Institute of Science and Technology Austria","file":[{"file_name":"Thesis_RokGrah_200727_convertedNew.pdf","creator":"rgrah","file_id":"8176","relation":"main_file","content_type":"application/pdf","file_size":16638998,"date_updated":"2020-07-27T12:00:07Z","access_level":"open_access","success":1,"date_created":"2020-07-27T12:00:07Z"},{"content_type":"application/zip","file_size":347459978,"date_updated":"2020-07-30T13:04:55Z","access_level":"closed","date_created":"2020-07-27T12:02:23Z","creator":"rgrah","file_name":"Thesis_new.zip","relation":"main_file","file_id":"8177"}],"has_accepted_license":"1","status":"public","page":"310","citation":{"mla":"Grah, Rok. <i>Gene Regulation across Scales – How Biophysical Constraints Shape Evolution</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8155\">10.15479/AT:ISTA:8155</a>.","ama":"Grah R. Gene regulation across scales – how biophysical constraints shape evolution. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8155\">10.15479/AT:ISTA:8155</a>","apa":"Grah, R. (2020). <i>Gene regulation across scales – how biophysical constraints shape evolution</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8155\">https://doi.org/10.15479/AT:ISTA:8155</a>","ieee":"R. Grah, “Gene regulation across scales – how biophysical constraints shape evolution,” Institute of Science and Technology Austria, 2020.","ista":"Grah R. 2020. Gene regulation across scales – how biophysical constraints shape evolution. Institute of Science and Technology Austria.","short":"R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape Evolution, Institute of Science and Technology Austria, 2020.","chicago":"Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints Shape Evolution.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8155\">https://doi.org/10.15479/AT:ISTA:8155</a>."},"ddc":["530","570"],"day":"24","alternative_title":["ISTA Thesis"],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","OA_place":"publisher","supervisor":[{"full_name":"Guet, Calin C","first_name":"Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","last_name":"Tkačik","first_name":"Gašper","full_name":"Tkačik, Gašper"}],"oa":1,"_id":"8155","related_material":{"record":[{"status":"public","id":"7675","relation":"part_of_dissertation"},{"id":"7569","relation":"part_of_dissertation","status":"public"},{"id":"7652","relation":"part_of_dissertation","status":"public"}]},"date_published":"2020-07-24T00:00:00Z","language":[{"iso":"eng"}],"publication_status":"published","degree_awarded":"PhD","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"title":"Gene regulation across scales – how biophysical constraints shape evolution","date_created":"2020-07-23T09:51:28Z","oa_version":"Published Version","doi":"10.15479/AT:ISTA:8155","article_processing_charge":"No","file_date_updated":"2020-07-30T13:04:55Z","type":"dissertation","month":"07","abstract":[{"text":"In the thesis we focus on the interplay of the biophysics and evolution of gene regulation. We start by addressing how the type of prokaryotic gene regulation – activation and repression – affects spurious binding to DNA, also known as\r\ntranscriptional crosstalk. We propose that regulatory interference caused by excess regulatory proteins in the dense cellular medium – global crosstalk – could be a factor in determining which type of gene regulatory network is evolutionarily preferred. Next,we use a normative approach in eukaryotic gene regulation to describe minimal\r\nnon-equilibrium enhancer models that optimize so-called regulatory phenotypes. We find a class of models that differ from standard thermodynamic equilibrium models by a single parameter that notably increases the regulatory performance. Next chapter addresses the question of genotype-phenotype-fitness maps of higher dimensional phenotypes. We show that our biophysically realistic approach allows us to understand how the mechanisms of promoter function constrain genotypephenotype maps, and how they affect the evolutionary trajectories of promoters.\r\nIn the last chapter we ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using mathematical modeling, we show that amplifications can tune gene expression in many environments, including those where transcription factor-based schemes are\r\nhard to evolve or maintain. ","lang":"eng"}],"project":[{"name":"Biophysically realistic genotype-phenotype maps for regulatory networks","_id":"267C84F4-B435-11E9-9278-68D0E5697425"}],"publication_identifier":{"issn":["2663-337X"]},"acknowledgement":"For the duration of his PhD, Rok was a recipient of a DOC fellowship of the Austrian Academy of Sciences.","corr_author":"1"},{"date_published":"2020-04-09T00:00:00Z","date_updated":"2026-04-08T07:25:08Z","author":[{"last_name":"Grah","first_name":"Rok","full_name":"Grah, Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2539-3560"},{"full_name":"Zoller, Benjamin","first_name":"Benjamin","last_name":"Zoller"},{"last_name":"Tkačik","first_name":"Gašper","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455"}],"year":"2020","related_material":{"record":[{"relation":"dissertation_contains","id":"8155","status":"public"}]},"_id":"7675","citation":{"ieee":"R. Grah, B. Zoller, and G. Tkačik, “Normative models of enhancer function,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory, 2020.","apa":"Grah, R., Zoller, B., &#38; Tkačik, G. (2020). Normative models of enhancer function. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.04.08.029405\">https://doi.org/10.1101/2020.04.08.029405</a>","mla":"Grah, Rok, et al. “Normative Models of Enhancer Function.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, 2020, doi:<a href=\"https://doi.org/10.1101/2020.04.08.029405\">10.1101/2020.04.08.029405</a>.","ama":"Grah R, Zoller B, Tkačik G. Normative models of enhancer function. <i>bioRxiv</i>. 2020. doi:<a href=\"https://doi.org/10.1101/2020.04.08.029405\">10.1101/2020.04.08.029405</a>","ista":"Grah R, Zoller B, Tkačik G. 2020. Normative models of enhancer function. bioRxiv, <a href=\"https://doi.org/10.1101/2020.04.08.029405\">10.1101/2020.04.08.029405</a>.","chicago":"Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Normative Models of Enhancer Function.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, 2020. <a href=\"https://doi.org/10.1101/2020.04.08.029405\">https://doi.org/10.1101/2020.04.08.029405</a>.","short":"R. Grah, B. Zoller, G. Tkačik, BioRxiv (2020)."},"status":"public","publication":"bioRxiv","publication_status":"published","language":[{"iso":"eng"}],"publisher":"Cold Spring Harbor Laboratory","doi":"10.1101/2020.04.08.029405","date_created":"2020-04-23T10:12:51Z","oa_version":"Preprint","article_processing_charge":"No","main_file_link":[{"url":"https://doi.org/10.1101/2020.04.08.029405 ","open_access":"1"}],"title":"Normative models of enhancer function","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"09","corr_author":"1","oa":1,"project":[{"_id":"2665AAFE-B435-11E9-9278-68D0E5697425","name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?","grant_number":"RGP0034/2018"},{"_id":"267C84F4-B435-11E9-9278-68D0E5697425","name":"Biophysically realistic genotype-phenotype maps for regulatory networks"}],"month":"04","type":"preprint","abstract":[{"lang":"eng","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."}]},{"pmid":1,"intvolume":"        14","publication_status":"published","language":[{"iso":"eng"}],"date_published":"2020-03-13T00:00:00Z","_id":"7656","isi":1,"publication_identifier":{"eissn":["1662-5188"]},"external_id":{"isi":["000525543200001"],"pmid":["32231528"]},"type":"journal_article","file_date_updated":"2020-07-14T12:48:01Z","month":"03","abstract":[{"lang":"eng","text":"We propose that correlations among neurons are generically strong enough to organize neural activity patterns into a discrete set of clusters, which can each be viewed as a population codeword. Our reasoning starts with the analysis of retinal ganglion cell data using maximum entropy models, showing that the population is robustly in a frustrated, marginally sub-critical, or glassy, state. This leads to an argument that neural populations in many other brain areas might share this structure. Next, we use latent variable models to show that this glassy state possesses well-defined clusters of neural activity. Clusters have three appealing properties: (i) clusters exhibit error correction, i.e., they are reproducibly elicited by the same stimulus despite variability at the level of constituent neurons; (ii) clusters encode qualitatively different visual features than their constituent neurons; and (iii) clusters can be learned by downstream neural circuits in an unsupervised fashion. We hypothesize that these properties give rise to a “learnable” neural code which the cortical hierarchy uses to extract increasingly complex features without supervision or reinforcement."}],"date_created":"2020-04-12T22:00:40Z","oa_version":"Published Version","doi":"10.3389/fncom.2020.00020","article_processing_charge":"No","title":"Clustering of neural activity: A design principle for population codes","department":[{"_id":"GaTk"}],"ddc":["570"],"article_number":"20","citation":{"short":"M.J. Berry, G. Tkačik, Frontiers in Computational Neuroscience 14 (2020).","ista":"Berry MJ, Tkačik G. 2020. Clustering of neural activity: A design principle for population codes. Frontiers in Computational Neuroscience. 14, 20.","chicago":"Berry, Michael J., and Gašper Tkačik. “Clustering of Neural Activity: A Design Principle for Population Codes.” <i>Frontiers in Computational Neuroscience</i>. Frontiers, 2020. <a href=\"https://doi.org/10.3389/fncom.2020.00020\">https://doi.org/10.3389/fncom.2020.00020</a>.","ieee":"M. J. Berry and G. Tkačik, “Clustering of neural activity: A design principle for population codes,” <i>Frontiers in Computational Neuroscience</i>, vol. 14. Frontiers, 2020.","mla":"Berry, Michael J., and Gašper Tkačik. “Clustering of Neural Activity: A Design Principle for Population Codes.” <i>Frontiers in Computational Neuroscience</i>, vol. 14, 20, Frontiers, 2020, doi:<a href=\"https://doi.org/10.3389/fncom.2020.00020\">10.3389/fncom.2020.00020</a>.","ama":"Berry MJ, Tkačik G. Clustering of neural activity: A design principle for population codes. <i>Frontiers in Computational Neuroscience</i>. 2020;14. doi:<a href=\"https://doi.org/10.3389/fncom.2020.00020\">10.3389/fncom.2020.00020</a>","apa":"Berry, M. J., &#38; Tkačik, G. (2020). Clustering of neural activity: A design principle for population codes. <i>Frontiers in Computational Neuroscience</i>. Frontiers. <a href=\"https://doi.org/10.3389/fncom.2020.00020\">https://doi.org/10.3389/fncom.2020.00020</a>"},"publication":"Frontiers in Computational Neuroscience","status":"public","publisher":"Frontiers","file":[{"creator":"dernst","file_name":"2020_Frontiers_Berry.pdf","relation":"main_file","file_id":"7659","date_updated":"2020-07-14T12:48:01Z","access_level":"open_access","date_created":"2020-04-14T12:20:39Z","file_size":4082937,"checksum":"2b1da23823eae9cedbb42d701945b61e","content_type":"application/pdf"}],"scopus_import":"1","has_accepted_license":"1","date_updated":"2026-04-16T08:28:50Z","author":[{"full_name":"Berry, Michael J.","first_name":"Michael J.","last_name":"Berry"},{"full_name":"Tkačik, Gašper","first_name":"Gašper","last_name":"Tkačik","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455"}],"year":"2020","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"article_type":"original","quality_controlled":"1","volume":14,"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","day":"13"},{"oa":1,"supervisor":[{"last_name":"Tkačik","first_name":"Gašper","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455"},{"orcid":"0000-0003-4398-476X","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","first_name":"Mark Tobias","last_name":"Bollenbach","full_name":"Bollenbach, Mark Tobias"}],"alternative_title":["ISTA Thesis"],"day":"14","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","OA_place":"publisher","status":"public","page":"271","ddc":["571","530","570"],"citation":{"ieee":"B. Kavcic, “Perturbations of protein synthesis: from antibiotics to genetics and physiology,” Institute of Science and Technology Austria, 2020.","apa":"Kavcic, B. (2020). <i>Perturbations of protein synthesis: from antibiotics to genetics and physiology</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:8657\">https://doi.org/10.15479/AT:ISTA:8657</a>","ama":"Kavcic B. Perturbations of protein synthesis: from antibiotics to genetics and physiology. 2020. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8657\">10.15479/AT:ISTA:8657</a>","mla":"Kavcic, Bor. <i>Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology</i>. Institute of Science and Technology Austria, 2020, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:8657\">10.15479/AT:ISTA:8657</a>.","ista":"Kavcic B. 2020. Perturbations of protein synthesis: from antibiotics to genetics and physiology. Institute of Science and Technology Austria.","chicago":"Kavcic, Bor. “Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology.” Institute of Science and Technology Austria, 2020. <a href=\"https://doi.org/10.15479/AT:ISTA:8657\">https://doi.org/10.15479/AT:ISTA:8657</a>.","short":"B. Kavcic, Perturbations of Protein Synthesis: From Antibiotics to Genetics and Physiology, Institute of Science and Technology Austria, 2020."},"has_accepted_license":"1","file":[{"file_name":"kavcicB_thesis202009.pdf","creator":"bkavcic","file_id":"8663","relation":"main_file","embargo":"2021-10-06","access_level":"open_access","date_updated":"2021-10-07T22:30:03Z","date_created":"2020-10-15T06:41:20Z","file_size":52636162,"content_type":"application/pdf","checksum":"d708ecd62b6fcc3bc1feb483b8dbe9eb"},{"access_level":"closed","date_updated":"2021-10-07T22:30:03Z","date_created":"2020-10-15T06:41:53Z","embargo_to":"open_access","checksum":"bb35f2352a04db19164da609f00501f3","file_size":321681247,"content_type":"application/zip","file_name":"2020b.zip","creator":"bkavcic","file_id":"8664","relation":"source_file"}],"publisher":"Institute of Science and Technology Austria","date_updated":"2026-04-08T07:27:48Z","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"M-Shop"}],"year":"2020","author":[{"last_name":"Kavcic","first_name":"Bor","full_name":"Kavcic, Bor","orcid":"0000-0001-6041-254X","id":"350F91D2-F248-11E8-B48F-1D18A9856A87"}],"publication_identifier":{"isbn":["978-3-99078-011-4"],"issn":["2663-337X"]},"corr_author":"1","acknowledgement":"I thank Life Science Facilities for their continuous support with providing top-notch laboratory materials, keeping the devices humming, and coordinating the repairs and building of custom-designed laboratory equipment with the MIBA Machine shop.","abstract":[{"lang":"eng","text":"Synthesis of proteins – translation – is a fundamental process of life. Quantitative studies anchor translation into the context of bacterial physiology and reveal several mathematical relationships, called “growth laws,” which capture physiological feedbacks between protein synthesis and cell growth. Growth laws describe the dependency of the ribosome abundance as a function of growth rate, which can change depending on the growth conditions. Perturbations of translation reveal that bacteria employ a compensatory strategy in which the reduced translation capability results in increased expression of the translation machinery.\r\nPerturbations of translation are achieved in various ways; clinically interesting is the application of translation-targeting antibiotics – translation inhibitors. The antibiotic effects on bacterial physiology are often poorly understood. Bacterial responses to two or more simultaneously applied antibiotics are even more puzzling. The combined antibiotic effect determines the type of drug interaction, which ranges from synergy (the effect is stronger than expected) to antagonism (the effect is weaker) and suppression (one of the drugs loses its potency).\r\nIn the first part of this work, we systematically measure the pairwise interaction network for translation inhibitors that interfere with different steps in translation. We find that the interactions are surprisingly diverse and tend to be more antagonistic. To explore the underlying mechanisms, we begin with a minimal biophysical model of combined antibiotic action. We base this model on the kinetics of antibiotic uptake and binding together with the physiological response described by the growth laws. The biophysical model explains some drug interactions, but not all; it specifically fails to predict suppression.\r\nIn the second part of this work, we hypothesize that elusive suppressive drug interactions result from the interplay between ribosomes halted in different stages of translation. To elucidate this putative mechanism of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using in- ducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks partially causes these interactions.\r\nWe extend this approach by varying two translation bottlenecks simultaneously. This approach reveals the suppression of translocation inhibition by inhibited translation. We rationalize this effect by modeling dense traffic of ribosomes that move on transcripts in a translation factor-mediated manner. This model predicts a dissolution of traffic jams caused by inhibited translocation when the density of ribosome traffic is reduced by lowered initiation. We base this model on the growth laws and quantitative relationships between different translation and growth parameters.\r\nIn the final part of this work, we describe a set of tools aimed at quantification of physiological and translation parameters. We further develop a simple model that directly connects the abundance of a translation factor with the growth rate, which allows us to extract physiological parameters describing initiation. We demonstrate the development of tools for measuring translation rate.\r\nThis thesis showcases how a combination of high-throughput growth rate mea- surements, genetics, and modeling can reveal mechanisms of drug interactions. Furthermore, by a gradual transition from combinations of antibiotics to precise genetic interventions, we demonstrated the equivalency between genetic and chemi- cal perturbations of translation. These findings tile the path for quantitative studies of antibiotic combinations and illustrate future approaches towards the quantitative description of translation."}],"type":"dissertation","file_date_updated":"2021-10-07T22:30:03Z","month":"10","title":"Perturbations of protein synthesis: from antibiotics to genetics and physiology","article_processing_charge":"No","doi":"10.15479/AT:ISTA:8657","oa_version":"Published Version","date_created":"2020-10-13T16:46:14Z","department":[{"_id":"GaTk"}],"degree_awarded":"PhD","publication_status":"published","language":[{"iso":"eng"}],"date_published":"2020-10-14T00:00:00Z","_id":"8657","related_material":{"record":[{"relation":"part_of_dissertation","id":"7673","status":"public"},{"id":"8250","relation":"part_of_dissertation","status":"public"}]}},{"publisher":"Springer Nature","file":[{"checksum":"986bebb308850a55850028d3d2b5b664","content_type":"application/pdf","file_size":1965672,"date_created":"2020-08-17T07:36:57Z","success":1,"date_updated":"2020-08-17T07:36:57Z","access_level":"open_access","file_id":"8275","relation":"main_file","file_name":"2020_NatureComm_Kavcic.pdf","creator":"dernst"}],"has_accepted_license":"1","scopus_import":"1","status":"public","publication":"Nature Communications","ddc":["570"],"citation":{"ieee":"B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Mechanisms of drug interactions between translation-inhibiting antibiotics,” <i>Nature Communications</i>, vol. 11. Springer Nature, 2020.","apa":"Kavcic, B., Tkačik, G., &#38; Bollenbach, M. T. (2020). Mechanisms of drug interactions between translation-inhibiting antibiotics. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-020-17734-z\">https://doi.org/10.1038/s41467-020-17734-z</a>","ama":"Kavcic B, Tkačik G, Bollenbach MT. Mechanisms of drug interactions between translation-inhibiting antibiotics. <i>Nature Communications</i>. 2020;11. doi:<a href=\"https://doi.org/10.1038/s41467-020-17734-z\">10.1038/s41467-020-17734-z</a>","mla":"Kavcic, Bor, et al. “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.” <i>Nature Communications</i>, vol. 11, 4013, Springer Nature, 2020, doi:<a href=\"https://doi.org/10.1038/s41467-020-17734-z\">10.1038/s41467-020-17734-z</a>.","short":"B. Kavcic, G. Tkačik, M.T. Bollenbach, Nature Communications 11 (2020).","chicago":"Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Mechanisms of Drug Interactions between Translation-Inhibiting Antibiotics.” <i>Nature Communications</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41467-020-17734-z\">https://doi.org/10.1038/s41467-020-17734-z</a>.","ista":"Kavcic B, Tkačik G, Bollenbach MT. 2020. Mechanisms of drug interactions between translation-inhibiting antibiotics. Nature Communications. 11, 4013."},"article_number":"4013","author":[{"orcid":"0000-0001-6041-254X","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","first_name":"Bor","last_name":"Kavcic","full_name":"Kavcic, Bor"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","first_name":"Gašper","last_name":"Tkačik","full_name":"Tkačik, Gašper"},{"orcid":"0000-0003-4398-476X","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","last_name":"Bollenbach","first_name":"Tobias","full_name":"Bollenbach, Tobias"}],"year":"2020","date_updated":"2026-04-29T22:30:42Z","article_type":"original","quality_controlled":"1","oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"day":"11","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","volume":11,"language":[{"iso":"eng"}],"intvolume":"        11","publication_status":"published","pmid":1,"_id":"8250","related_material":{"record":[{"id":"8657","relation":"dissertation_contains","status":"public"}]},"isi":1,"date_published":"2020-08-11T00:00:00Z","type":"journal_article","file_date_updated":"2020-08-17T07:36:57Z","month":"08","abstract":[{"text":"Antibiotics that interfere with translation, when combined, interact in diverse and difficult-to-predict ways. Here, we explain these interactions by “translation bottlenecks”: points in the translation cycle where antibiotics block ribosomal progression. To elucidate the underlying mechanisms of drug interactions between translation inhibitors, we generate translation bottlenecks genetically using inducible control of translation factors that regulate well-defined translation cycle steps. These perturbations accurately mimic antibiotic action and drug interactions, supporting that the interplay of different translation bottlenecks causes these interactions. We further show that growth laws, combined with drug uptake and binding kinetics, enable the direct prediction of a large fraction of observed interactions, yet fail to predict suppression. However, varying two translation bottlenecks simultaneously supports that dense traffic of ribosomes and competition for translation factors account for the previously unexplained suppression. These results highlight the importance of “continuous epistasis” in bacterial physiology.","lang":"eng"}],"external_id":{"pmid":["32782250"],"isi":["000562769300008"]},"project":[{"call_identifier":"FWF","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","grant_number":"P27201-B22","name":"Revealing the mechanisms underlying drug interactions"},{"call_identifier":"FWF","_id":"254E9036-B435-11E9-9278-68D0E5697425","name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27"}],"publication_identifier":{"issn":["2041-1723"]},"acknowledgement":"We thank M. Hennessey-Wesen, I. Tomanek, K. Jain, A. Staron, K. Tomasek, M. Scott,\r\nK.C. Huang, and Z. Gitai for reading the manuscript and constructive comments. B.K. is\r\nindebted to C. Guet for additional guidance and generous support, which rendered this\r\nwork possible. B.K. thanks all members of Guet group for many helpful discussions and\r\nsharing of resources. B.K. additionally acknowledges the tremendous support from A.\r\nAngermayr and K. Mitosch with experimental work. We further thank E. Brown for\r\nhelpful comments regarding lamotrigine, and A. Buskirk for valuable suggestions\r\nregarding the ribosome footprint size. This work was supported in part by Austrian\r\nScience Fund (FWF) standalone grants P 27201-B22 (to T.B.) and P 28844 (to G.T.),\r\nHFSP program Grant RGP0042/2013 (to T.B.), German Research Foundation (DFG)\r\nstandalone grant BO 3502/2-1 (to T.B.), and German Research Foundation (DFG)\r\nCollaborative Research Centre (SFB) 1310 (to T.B.). Open access funding provided by\r\nProjekt DEAL.","department":[{"_id":"GaTk"}],"title":"Mechanisms of drug interactions between translation-inhibiting antibiotics","doi":"10.1038/s41467-020-17734-z","oa_version":"Published Version","date_created":"2020-08-12T09:13:50Z","article_processing_charge":"No"},{"day":"18","department":[{"_id":"GaTk"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"A minimal biophysical model of combined antibiotic action","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2020.04.18.047886 "}],"article_processing_charge":"No","doi":"10.1101/2020.04.18.047886","oa_version":"Preprint","date_created":"2020-04-22T08:27:56Z","abstract":[{"text":"Combining drugs can improve the efficacy of treatments. However, predicting the effect of drug combinations is still challenging. The combined potency of drugs determines the drug interaction, which is classified as synergistic, additive, antagonistic, or suppressive. While probabilistic, non-mechanistic models exist, there is currently no biophysical model that can predict antibiotic interactions. Here, we present a physiologically relevant model of the combined action of antibiotics that inhibit protein synthesis by targeting the ribosome. This model captures the kinetics of antibiotic binding and transport, and uses bacterial growth laws to predict growth in the presence of antibiotic combinations. We find that this biophysical model can produce all drug interaction types except suppression. We show analytically that antibiotics which cannot bind to the ribosome simultaneously generally act as substitutes for one another, leading to additive drug interactions. Previously proposed null expectations for higher-order drug interactions follow as a limiting case of our model. We further extend the model to include the effects of direct physical or allosteric interactions between individual drugs on the ribosome. Notably, such direct interactions profoundly change the combined drug effect, depending on the kinetic parameters of the drugs used. The model makes additional predictions for the effects of resistance genes on drug interactions and for interactions between ribosome-targeting antibiotics and antibiotics with other targets. These findings enhance our understanding of the interplay between drug action and cell physiology and are a key step toward a general framework for predicting drug interactions.","lang":"eng"}],"month":"04","type":"preprint","project":[{"grant_number":"P27201-B22","name":"Revealing the mechanisms underlying drug interactions","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"call_identifier":"FWF","_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27","name":"Biophysics of information processing in gene regulation"}],"oa":1,"related_material":{"record":[{"id":"8997","relation":"later_version","status":"public"},{"status":"public","relation":"dissertation_contains","id":"8657"}]},"_id":"7673","year":"2020","author":[{"full_name":"Kavcic, Bor","first_name":"Bor","last_name":"Kavcic","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6041-254X"},{"full_name":"Tkačik, Gašper","first_name":"Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"},{"id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X","last_name":"Bollenbach","first_name":"Tobias","full_name":"Bollenbach, Tobias"}],"date_updated":"2026-04-29T22:30:42Z","date_published":"2020-04-18T00:00:00Z","publisher":"Cold Spring Harbor Laboratory","language":[{"iso":"eng"}],"publication_status":"published","publication":"bioRxiv","status":"public","citation":{"ama":"Kavcic B, Tkačik G, Bollenbach MT. A minimal biophysical model of combined antibiotic action. <i>bioRxiv</i>. 2020. doi:<a href=\"https://doi.org/10.1101/2020.04.18.047886\">10.1101/2020.04.18.047886</a>","ieee":"B. Kavcic, G. Tkačik, and M. T. Bollenbach, “A minimal biophysical model of combined antibiotic action,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory, 2020.","apa":"Kavcic, B., Tkačik, G., &#38; Bollenbach, M. T. (2020). A minimal biophysical model of combined antibiotic action. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.04.18.047886\">https://doi.org/10.1101/2020.04.18.047886</a>","mla":"Kavcic, Bor, et al. “A Minimal Biophysical Model of Combined Antibiotic Action.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, 2020, doi:<a href=\"https://doi.org/10.1101/2020.04.18.047886\">10.1101/2020.04.18.047886</a>.","short":"B. Kavcic, G. Tkačik, M.T. Bollenbach, BioRxiv (2020).","ista":"Kavcic B, Tkačik G, Bollenbach MT. 2020. A minimal biophysical model of combined antibiotic action. bioRxiv, <a href=\"https://doi.org/10.1101/2020.04.18.047886\">10.1101/2020.04.18.047886</a>.","chicago":"Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “A Minimal Biophysical Model of Combined Antibiotic Action.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, 2020. <a href=\"https://doi.org/10.1101/2020.04.18.047886\">https://doi.org/10.1101/2020.04.18.047886</a>."}},{"article_processing_charge":"No","oa_version":"Submitted Version","date_created":"2020-04-08T15:20:53Z","doi":"10.1038/s41559-020-1132-7","title":"Gene amplification as a form of population-level gene expression regulation","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"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.","publication_identifier":{"issn":["2397-334X"]},"project":[{"_id":"267C84F4-B435-11E9-9278-68D0E5697425","name":"Biophysically realistic genotype-phenotype maps for regulatory networks"}],"external_id":{"pmid":["32152532"],"isi":["000519008300005"]},"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"}],"type":"journal_article","file_date_updated":"2020-10-09T09:56:01Z","month":"04","date_published":"2020-04-01T00:00:00Z","related_material":{"record":[{"relation":"research_data","id":"7016","status":"public"},{"relation":"research_data","id":"7383","status":"public"},{"status":"public","relation":"dissertation_contains","id":"8155"},{"status":"public","id":"8653","relation":"used_in_publication"}],"link":[{"url":"https://ist.ac.at/en/news/how-to-thrive-without-gene-regulation/","relation":"press_release","description":"News on IST Homepage"}]},"_id":"7652","isi":1,"pmid":1,"publication_status":"published","intvolume":"         4","language":[{"iso":"eng"}],"issue":"4","volume":4,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"01","oa":1,"quality_controlled":"1","article_type":"original","date_updated":"2026-04-29T22:30:48Z","year":"2020","author":[{"id":"3981F020-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6197-363X","full_name":"Tomanek, Isabella","first_name":"Isabella","last_name":"Tomanek"},{"id":"483E70DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2539-3560","first_name":"Rok","last_name":"Grah","full_name":"Grah, Rok"},{"first_name":"M.","last_name":"Lagator","full_name":"Lagator, M."},{"full_name":"Andersson, A. M. C.","first_name":"A. M. C.","last_name":"Andersson"},{"first_name":"Jonathan P","last_name":"Bollback","full_name":"Bollback, Jonathan P","id":"2C6FA9CC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4624-4612"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","last_name":"Tkačik","first_name":"Gašper","full_name":"Tkačik, Gašper"},{"orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C"}],"ddc":["570"],"citation":{"short":"I. Tomanek, R. Grah, M. Lagator, A.M.C. Andersson, J.P. Bollback, G. Tkačik, C.C. Guet, Nature Ecology &#38; Evolution 4 (2020) 612–625.","chicago":"Tomanek, Isabella, Rok Grah, M. Lagator, A. M. C. Andersson, Jonathan P Bollback, Gašper Tkačik, and Calin C Guet. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” <i>Nature Ecology &#38; Evolution</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41559-020-1132-7\">https://doi.org/10.1038/s41559-020-1132-7</a>.","ista":"Tomanek I, Grah R, Lagator M, Andersson AMC, Bollback JP, Tkačik G, Guet CC. 2020. Gene amplification as a form of population-level gene expression regulation. Nature Ecology &#38; Evolution. 4(4), 612–625.","mla":"Tomanek, Isabella, et al. “Gene Amplification as a Form of Population-Level Gene Expression Regulation.” <i>Nature Ecology &#38; Evolution</i>, vol. 4, no. 4, Springer Nature, 2020, pp. 612–25, doi:<a href=\"https://doi.org/10.1038/s41559-020-1132-7\">10.1038/s41559-020-1132-7</a>.","ama":"Tomanek I, Grah R, Lagator M, et al. Gene amplification as a form of population-level gene expression regulation. <i>Nature Ecology &#38; Evolution</i>. 2020;4(4):612-625. doi:<a href=\"https://doi.org/10.1038/s41559-020-1132-7\">10.1038/s41559-020-1132-7</a>","apa":"Tomanek, I., Grah, R., Lagator, M., Andersson, A. M. C., Bollback, J. P., Tkačik, G., &#38; Guet, C. C. (2020). Gene amplification as a form of population-level gene expression regulation. <i>Nature Ecology &#38; Evolution</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41559-020-1132-7\">https://doi.org/10.1038/s41559-020-1132-7</a>","ieee":"I. Tomanek <i>et al.</i>, “Gene amplification as a form of population-level gene expression regulation,” <i>Nature Ecology &#38; Evolution</i>, vol. 4, no. 4. Springer Nature, pp. 612–625, 2020."},"page":"612-625","publication":"Nature Ecology & Evolution","status":"public","has_accepted_license":"1","scopus_import":"1","publisher":"Springer Nature","file":[{"file_name":"2020_NatureEcolEvo_Tomanek.pdf","creator":"dernst","file_id":"8640","relation":"main_file","access_level":"open_access","date_updated":"2020-10-09T09:56:01Z","success":1,"date_created":"2020-10-09T09:56:01Z","file_size":745242,"content_type":"application/pdf","checksum":"ef3bbf42023e30b2c24a6278025d2040"}]},{"_id":"19988","date_published":"2019-09-01T00:00:00Z","language":[{"iso":"eng"}],"publication_status":"published","department":[{"_id":"GaTk"}],"title":"The Essential Role of Thermodynamics in Metabolic Network Modeling: Physical Insights and Computational Challenges","doi":"10.1142/9781786347015_0018","oa_version":"Preprint","date_created":"2025-07-10T13:34:01Z","article_processing_charge":"No","main_file_link":[{"open_access":"1","url":"https://doi.org/10.48550/arXiv.1902.07129"}],"type":"book_chapter","month":"09","arxiv":1,"abstract":[{"text":"Quantitative studies of cell metabolism are often based on large chemical reaction network models. A steady-state approach is suited to analyze phenomena on the timescale of cell growth and circumvents the problem of incomplete experimental knowledge on kinetic laws and parameters, but it should be supported by a correct implementation of thermodynamic constraints. In this chapter, we review the latter aspect, highlighting its computational challenges and physical insights. The simple introduction of Gibbs inequalities avoids the presence of unfeasible loops allowing for correct timescale analysis, but leads to possibly non-convex feasible flux spaces whose exploration needs efficient algorithms. We briefly review the implementation of thermodynamics through variational principles in constraint-based models of metabolic networks.","lang":"eng"}],"external_id":{"arxiv":["1902.07129"]},"publication_identifier":{"eisbn":["9781786347022"],"isbn":["9781786347008"]},"author":[{"full_name":"De Martino, A","first_name":"A","last_name":"De Martino"},{"last_name":"De Martino","first_name":"Daniele","full_name":"De Martino, Daniele","orcid":"0000-0002-5214-4706","id":"3FF5848A-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Marinari","first_name":"E","full_name":"Marinari, E"}],"year":"2019","date_updated":"2025-09-23T11:53:34Z","publisher":"World Scientific Publishing","publication":"Chemical Kinetics","status":"public","citation":{"mla":"De Martino, A., et al. “The Essential Role of Thermodynamics in Metabolic Network Modeling: Physical Insights and Computational Challenges.” <i>Chemical Kinetics</i>, World Scientific Publishing, 2019, pp. 455–71, doi:<a href=\"https://doi.org/10.1142/9781786347015_0018\">10.1142/9781786347015_0018</a>.","apa":"De Martino, A., De Martino, D., &#38; Marinari, E. (2019). The Essential Role of Thermodynamics in Metabolic Network Modeling: Physical Insights and Computational Challenges. In <i>Chemical Kinetics</i> (pp. 455–471). World Scientific Publishing. <a href=\"https://doi.org/10.1142/9781786347015_0018\">https://doi.org/10.1142/9781786347015_0018</a>","ieee":"A. De Martino, D. De Martino, and E. Marinari, “The Essential Role of Thermodynamics in Metabolic Network Modeling: Physical Insights and Computational Challenges,” in <i>Chemical Kinetics</i>, World Scientific Publishing, 2019, pp. 455–471.","ama":"De Martino A, De Martino D, Marinari E. The Essential Role of Thermodynamics in Metabolic Network Modeling: Physical Insights and Computational Challenges. In: <i>Chemical Kinetics</i>. World Scientific Publishing; 2019:455-471. doi:<a href=\"https://doi.org/10.1142/9781786347015_0018\">10.1142/9781786347015_0018</a>","ista":"De Martino A, De Martino D, Marinari E. 2019.The Essential Role of Thermodynamics in Metabolic Network Modeling: Physical Insights and Computational Challenges. In: Chemical Kinetics. , 455–471.","chicago":"De Martino, A, Daniele De Martino, and E Marinari. “The Essential Role of Thermodynamics in Metabolic Network Modeling: Physical Insights and Computational Challenges.” In <i>Chemical Kinetics</i>, 455–71. World Scientific Publishing, 2019. <a href=\"https://doi.org/10.1142/9781786347015_0018\">https://doi.org/10.1142/9781786347015_0018</a>.","short":"A. De Martino, D. De Martino, E. Marinari, in:, Chemical Kinetics, World Scientific Publishing, 2019, pp. 455–471."},"OA_type":"green","page":"455-471","day":"01","OA_place":"repository","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","oa":1},{"publication_status":"published","intvolume":"       116","pmid":1,"language":[{"iso":"eng"}],"date_published":"2019-02-19T00:00:00Z","_id":"196","related_material":{"link":[{"description":"News on IST Webpage","relation":"press_release","url":"https://ist.ac.at/en/news/famous-sandpile-model-shown-to-move-like-a-traveling-sand-dune/"}]},"isi":1,"publication_identifier":{"eissn":["1091-6490"]},"corr_author":"1","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","abstract":[{"lang":"eng","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. "}],"month":"02","arxiv":1,"type":"journal_article","external_id":{"pmid":[" 30728300"],"isi":["000459074400013"],"arxiv":["1806.10823"]},"title":"Harmonic dynamics of the Abelian sandpile","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1073/pnas.1812015116"}],"article_processing_charge":"No","doi":"10.1073/pnas.1812015116","date_created":"2018-12-11T11:45:08Z","oa_version":"Published Version","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"TaHa"}],"publication":"Proceedings of the National Academy of Sciences of the United States of America","status":"public","page":"2821-2830","citation":{"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.","chicago":"Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2019. <a href=\"https://doi.org/10.1073/pnas.1812015116\">https://doi.org/10.1073/pnas.1812015116</a>.","ama":"Lang M, Shkolnikov M. Harmonic dynamics of the Abelian sandpile. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2019;116(8):2821-2830. doi:<a href=\"https://doi.org/10.1073/pnas.1812015116\">10.1073/pnas.1812015116</a>","apa":"Lang, M., &#38; Shkolnikov, M. (2019). Harmonic dynamics of the Abelian sandpile. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.1812015116\">https://doi.org/10.1073/pnas.1812015116</a>","ieee":"M. Lang and M. Shkolnikov, “Harmonic dynamics of the Abelian sandpile,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 116, no. 8. National Academy of Sciences, pp. 2821–2830, 2019.","mla":"Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 116, no. 8, National Academy of Sciences, 2019, pp. 2821–30, doi:<a href=\"https://doi.org/10.1073/pnas.1812015116\">10.1073/pnas.1812015116</a>."},"scopus_import":"1","publisher":"National Academy of Sciences","date_updated":"2025-06-03T11:18:16Z","year":"2019","author":[{"full_name":"Lang, Moritz","first_name":"Moritz","last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Shkolnikov, Mikhail","first_name":"Mikhail","last_name":"Shkolnikov","id":"35084A62-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4310-178X"}],"quality_controlled":"1","article_type":"original","oa":1,"volume":116,"issue":"8","day":"19","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"date_updated":"2025-04-15T07:33:55Z","date_published":"2019-07-02T00:00:00Z","_id":"9786","related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"6784"}]},"author":[{"full_name":"Ruess, Jakob","first_name":"Jakob","last_name":"Ruess","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1615-3282"},{"last_name":"Pleska","first_name":"Maros","full_name":"Pleska, Maros","id":"4569785E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7460-7479"},{"last_name":"Guet","first_name":"Calin C","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Tkačik, Gašper","first_name":"Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"year":"2019","status":"public","citation":{"apa":"Ruess, J., Pleska, M., Guet, C. C., &#38; Tkačik, G. (2019). Supporting text and results. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1007168.s001\">https://doi.org/10.1371/journal.pcbi.1007168.s001</a>","mla":"Ruess, Jakob, et al. <i>Supporting Text and Results</i>. Public Library of Science, 2019, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007168.s001\">10.1371/journal.pcbi.1007168.s001</a>.","ieee":"J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Supporting text and results.” Public Library of Science, 2019.","ama":"Ruess J, Pleska M, Guet CC, Tkačik G. Supporting text and results. 2019. doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007168.s001\">10.1371/journal.pcbi.1007168.s001</a>","ista":"Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Supporting text and results, Public Library of Science, <a href=\"https://doi.org/10.1371/journal.pcbi.1007168.s001\">10.1371/journal.pcbi.1007168.s001</a>.","chicago":"Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Supporting Text and Results.” Public Library of Science, 2019. <a href=\"https://doi.org/10.1371/journal.pcbi.1007168.s001\">https://doi.org/10.1371/journal.pcbi.1007168.s001</a>.","short":"J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, (2019)."},"publisher":"Public Library of Science","title":"Supporting text and results","doi":"10.1371/journal.pcbi.1007168.s001","oa_version":"Published Version","date_created":"2021-08-06T08:23:43Z","article_processing_charge":"No","day":"02","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"user_id":"6785fbc1-c503-11eb-8a32-93094b40e1cf","month":"07","type":"research_data_reference"},{"language":[{"iso":"eng"}],"pmid":1,"intvolume":"        15","publication_status":"published","isi":1,"_id":"5817","date_published":"2019-01-10T00:00:00Z","external_id":{"pmid":["30629082"],"isi":["000457329700003"]},"type":"journal_article","month":"01","file_date_updated":"2020-10-09T11:00:05Z","abstract":[{"lang":"eng","text":"We theoretically study the shapes of lipid vesicles confined to a spherical cavity, elaborating a framework based on the so-called limiting shapes constructed from geometrically simple structural elements such as double-membrane walls and edges. Partly inspired by numerical results, the proposed non-compartmentalized and compartmentalized limiting shapes are arranged in the bilayer-couple phase diagram which is then compared to its free-vesicle counterpart. We also compute the area-difference-elasticity phase diagram of the limiting shapes and we use it to interpret shape transitions experimentally observed in vesicles confined within another vesicle. The limiting-shape framework may be generalized to theoretically investigate the structure of certain cell organelles such as the mitochondrion."}],"corr_author":"1","publication_identifier":{"eissn":["1744-6848"],"issn":["1744-683X"]},"department":[{"_id":"GaTk"}],"date_created":"2019-01-11T07:37:47Z","license":"https://creativecommons.org/licenses/by-nc-nd/3.0/","oa_version":"Submitted Version","doi":"10.1039/c8sm01956h","article_processing_charge":"No","title":"Limiting shapes of confined lipid vesicles","publisher":"Royal Society of Chemistry","file":[{"file_size":5370762,"checksum":"614c337d6424ccd3d48d1b1f9513510d","content_type":"application/pdf","date_created":"2020-10-09T11:00:05Z","success":1,"access_level":"open_access","date_updated":"2020-10-09T11:00:05Z","relation":"main_file","file_id":"8641","creator":"bkavcic","file_name":"lmt_sftmtr_V8.pdf"}],"scopus_import":"1","has_accepted_license":"1","citation":{"mla":"Kavcic, Bor, et al. “Limiting Shapes of Confined Lipid Vesicles.” <i>Soft Matter</i>, vol. 15, no. 4, Royal Society of Chemistry, 2019, pp. 602–14, doi:<a href=\"https://doi.org/10.1039/c8sm01956h\">10.1039/c8sm01956h</a>.","ama":"Kavcic B, Sakashita A, Noguchi H, Ziherl P. Limiting shapes of confined lipid vesicles. <i>Soft Matter</i>. 2019;15(4):602-614. doi:<a href=\"https://doi.org/10.1039/c8sm01956h\">10.1039/c8sm01956h</a>","apa":"Kavcic, B., Sakashita, A., Noguchi, H., &#38; Ziherl, P. (2019). Limiting shapes of confined lipid vesicles. <i>Soft Matter</i>. Royal Society of Chemistry. <a href=\"https://doi.org/10.1039/c8sm01956h\">https://doi.org/10.1039/c8sm01956h</a>","ieee":"B. Kavcic, A. Sakashita, H. Noguchi, and P. Ziherl, “Limiting shapes of confined lipid vesicles,” <i>Soft Matter</i>, vol. 15, no. 4. Royal Society of Chemistry, pp. 602–614, 2019.","chicago":"Kavcic, Bor, A. Sakashita, H. Noguchi, and P. Ziherl. “Limiting Shapes of Confined Lipid Vesicles.” <i>Soft Matter</i>. Royal Society of Chemistry, 2019. <a href=\"https://doi.org/10.1039/c8sm01956h\">https://doi.org/10.1039/c8sm01956h</a>.","ista":"Kavcic B, Sakashita A, Noguchi H, Ziherl P. 2019. Limiting shapes of confined lipid vesicles. Soft Matter. 15(4), 602–614.","short":"B. Kavcic, A. Sakashita, H. Noguchi, P. Ziherl, Soft Matter 15 (2019) 602–614."},"page":"602-614","ddc":["530"],"publication":"Soft Matter","status":"public","author":[{"id":"350F91D2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6041-254X","full_name":"Kavcic, Bor","first_name":"Bor","last_name":"Kavcic"},{"last_name":"Sakashita","first_name":"A.","full_name":"Sakashita, A."},{"full_name":"Noguchi, H.","first_name":"H.","last_name":"Noguchi"},{"first_name":"P.","last_name":"Ziherl","full_name":"Ziherl, P."}],"year":"2019","date_updated":"2024-10-09T20:58:29Z","oa":1,"article_type":"original","quality_controlled":"1","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/3.0/legalcode","short":"CC BY-NC-ND (3.0)","image":"/images/cc_by_nc_nd.png"},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","day":"10","issue":"4","volume":15},{"external_id":{"pmid":["30712870"],"isi":["000457969200015"]},"project":[{"name":"Biophysics of information processing in gene regulation","grant_number":"P28844-B27","_id":"254E9036-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"type":"journal_article","month":"02","abstract":[{"text":"In developing organisms, spatially prescribed cell identities are thought to be determined by the expression levels of multiple genes. Quantitative tests of this idea, however, require a theoretical framework capable of exposing the rules and precision of cell specification over developmental time. We use the gap gene network in the early fly embryo as an example to show how expression levels of the four gap genes can be jointly decoded into an optimal specification of position with 1% accuracy. The decoder correctly predicts, with no free parameters, the dynamics of pair-rule expression patterns at different developmental time points and in various mutant backgrounds. Precise cellular identities are thus available at the earliest stages of development, contrasting the prevailing view of positional information being slowly refined across successive layers of the patterning network. Our results suggest that developmental enhancers closely approximate a mathematically optimal decoding strategy.","lang":"eng"}],"department":[{"_id":"GaTk"}],"date_created":"2019-02-10T22:59:16Z","oa_version":"Published Version","doi":"10.1016/j.cell.2019.01.007","article_processing_charge":"No","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.cell.2019.01.007"}],"title":"Optimal decoding of cellular identities in a genetic network","language":[{"iso":"eng"}],"pmid":1,"intvolume":"       176","publication_status":"published","_id":"5945","isi":1,"related_material":{"link":[{"url":"https://ist.ac.at/en/news/cells-find-their-identity-using-a-mathematically-optimal-strategy/","relation":"press_release","description":"News on IST Homepage"}]},"date_published":"2019-02-07T00:00:00Z","oa":1,"article_type":"original","quality_controlled":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","day":"07","issue":"4","volume":176,"publisher":"Cell Press","scopus_import":"1","page":"844-855.e15","citation":{"short":"M.D. Petkova, G. Tkačik, W. Bialek, E.F. Wieschaus, T. Gregor, Cell 176 (2019) 844–855.e15.","ista":"Petkova MD, Tkačik G, Bialek W, Wieschaus EF, Gregor T. 2019. Optimal decoding of cellular identities in a genetic network. Cell. 176(4), 844–855.e15.","chicago":"Petkova, Mariela D., Gašper Tkačik, William Bialek, Eric F. Wieschaus, and Thomas Gregor. “Optimal Decoding of Cellular Identities in a Genetic Network.” <i>Cell</i>. Cell Press, 2019. <a href=\"https://doi.org/10.1016/j.cell.2019.01.007\">https://doi.org/10.1016/j.cell.2019.01.007</a>.","ieee":"M. D. Petkova, G. Tkačik, W. Bialek, E. F. Wieschaus, and T. Gregor, “Optimal decoding of cellular identities in a genetic network,” <i>Cell</i>, vol. 176, no. 4. Cell Press, p. 844–855.e15, 2019.","ama":"Petkova MD, Tkačik G, Bialek W, Wieschaus EF, Gregor T. Optimal decoding of cellular identities in a genetic network. <i>Cell</i>. 2019;176(4):844-855.e15. doi:<a href=\"https://doi.org/10.1016/j.cell.2019.01.007\">10.1016/j.cell.2019.01.007</a>","apa":"Petkova, M. D., Tkačik, G., Bialek, W., Wieschaus, E. F., &#38; Gregor, T. (2019). Optimal decoding of cellular identities in a genetic network. <i>Cell</i>. Cell Press. <a href=\"https://doi.org/10.1016/j.cell.2019.01.007\">https://doi.org/10.1016/j.cell.2019.01.007</a>","mla":"Petkova, Mariela D., et al. “Optimal Decoding of Cellular Identities in a Genetic Network.” <i>Cell</i>, vol. 176, no. 4, Cell Press, 2019, p. 844–855.e15, doi:<a href=\"https://doi.org/10.1016/j.cell.2019.01.007\">10.1016/j.cell.2019.01.007</a>."},"status":"public","publication":"Cell","author":[{"first_name":"Mariela D.","last_name":"Petkova","full_name":"Petkova, Mariela D."},{"first_name":"Gasper","last_name":"Tkacik","full_name":"Tkacik, Gasper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455"},{"full_name":"Bialek, William","last_name":"Bialek","first_name":"William"},{"last_name":"Wieschaus","first_name":"Eric F.","full_name":"Wieschaus, Eric F."},{"full_name":"Gregor, Thomas","first_name":"Thomas","last_name":"Gregor"}],"year":"2019","date_updated":"2025-04-14T09:28:43Z"},{"_id":"6046","isi":1,"date_published":"2019-02-14T00:00:00Z","language":[{"iso":"eng"}],"pmid":1,"intvolume":"        15","publication_status":"published","department":[{"_id":"GaTk"}],"date_created":"2019-02-24T22:59:18Z","oa_version":"Submitted Version","doi":"10.15252/msb.20188470","article_processing_charge":"No","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pubmed/30765425"}],"title":"Temporal order and precision of complex stress responses in individual bacteria","external_id":{"isi":["000459628300003"],"pmid":["30765425"]},"project":[{"grant_number":"P27201-B22","name":"Revealing the mechanisms underlying drug interactions","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"Revealing the fundamental limits of cell growth","grant_number":"RGP0042/2013","_id":"25EB3A80-B435-11E9-9278-68D0E5697425"}],"type":"journal_article","month":"02","abstract":[{"lang":"eng","text":"Sudden stress often triggers diverse, temporally structured gene expression responses in microbes, but it is largely unknown how variable in time such responses are and if genes respond in the same temporal order in every single cell. Here, we quantified timing variability of individual promoters responding to sublethal antibiotic stress using fluorescent reporters, microfluidics, and time‐lapse microscopy. We identified lower and upper bounds that put definite constraints on timing variability, which varies strongly among promoters and conditions. Timing variability can be interpreted using results from statistical kinetics, which enable us to estimate the number of rate‐limiting molecular steps underlying different responses. We found that just a few critical steps control some responses while others rely on dozens of steps. To probe connections between different stress responses, we then tracked the temporal order and response time correlations of promoter pairs in individual cells. Our results support that, when bacteria are exposed to the antibiotic nitrofurantoin, the ensuing oxidative stress and SOS responses are part of the same causal chain of molecular events. In contrast, under trimethoprim, the acid stress response and the SOS response are part of different chains of events running in parallel. Our approach reveals fundamental constraints on gene expression timing and provides new insights into the molecular events that underlie the timing of stress responses."}],"author":[{"id":"39B66846-F248-11E8-B48F-1D18A9856A87","first_name":"Karin","last_name":"Mitosch","full_name":"Mitosch, Karin"},{"id":"34DA8BD6-F248-11E8-B48F-1D18A9856A87","full_name":"Rieckh, Georg","last_name":"Rieckh","first_name":"Georg"},{"orcid":"0000-0003-4398-476X","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","first_name":"Mark Tobias","last_name":"Bollenbach","full_name":"Bollenbach, Mark Tobias"}],"year":"2019","acknowledged_ssus":[{"_id":"Bio"}],"date_updated":"2025-04-15T08:09:37Z","publisher":"Embo Press","scopus_import":"1","citation":{"chicago":"Mitosch, Karin, Georg Rieckh, and Mark Tobias Bollenbach. “Temporal Order and Precision of Complex Stress Responses in Individual Bacteria.” <i>Molecular Systems Biology</i>. Embo Press, 2019. <a href=\"https://doi.org/10.15252/msb.20188470\">https://doi.org/10.15252/msb.20188470</a>.","short":"K. Mitosch, G. Rieckh, M.T. Bollenbach, Molecular Systems Biology 15 (2019).","ista":"Mitosch K, Rieckh G, Bollenbach MT. 2019. Temporal order and precision of complex stress responses in individual bacteria. Molecular systems biology. 15(2), e8470.","mla":"Mitosch, Karin, et al. “Temporal Order and Precision of Complex Stress Responses in Individual Bacteria.” <i>Molecular Systems Biology</i>, vol. 15, no. 2, e8470, Embo Press, 2019, doi:<a href=\"https://doi.org/10.15252/msb.20188470\">10.15252/msb.20188470</a>.","ieee":"K. Mitosch, G. Rieckh, and M. T. Bollenbach, “Temporal order and precision of complex stress responses in individual bacteria,” <i>Molecular systems biology</i>, vol. 15, no. 2. Embo Press, 2019.","apa":"Mitosch, K., Rieckh, G., &#38; Bollenbach, M. T. (2019). Temporal order and precision of complex stress responses in individual bacteria. <i>Molecular Systems Biology</i>. Embo Press. <a href=\"https://doi.org/10.15252/msb.20188470\">https://doi.org/10.15252/msb.20188470</a>","ama":"Mitosch K, Rieckh G, Bollenbach MT. Temporal order and precision of complex stress responses in individual bacteria. <i>Molecular systems biology</i>. 2019;15(2). doi:<a href=\"https://doi.org/10.15252/msb.20188470\">10.15252/msb.20188470</a>"},"article_number":"e8470","status":"public","publication":"Molecular systems biology","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","day":"14","issue":"2","volume":15,"oa":1,"quality_controlled":"1"},{"date_updated":"2025-04-15T06:50:24Z","year":"2019","author":[{"orcid":"0000-0002-5214-4706","id":"3FF5848A-F248-11E8-B48F-1D18A9856A87","full_name":"De Martino, Daniele","last_name":"De Martino","first_name":"Daniele"}],"ddc":["570"],"citation":{"chicago":"De Martino, Daniele. “Feedback-Induced Self-Oscillations in Large Interacting Systems Subjected to Phase Transitions.” <i>Journal of Physics A: Mathematical and Theoretical</i>. IOP Publishing, 2019. <a href=\"https://doi.org/10.1088/1751-8121/aaf2dd\">https://doi.org/10.1088/1751-8121/aaf2dd</a>.","short":"D. De Martino, Journal of Physics A: Mathematical and Theoretical 52 (2019).","ista":"De Martino D. 2019. Feedback-induced self-oscillations in large interacting systems subjected to phase transitions. Journal of Physics A: Mathematical and Theoretical. 52(4), 045002.","ama":"De Martino D. Feedback-induced self-oscillations in large interacting systems subjected to phase transitions. <i>Journal of Physics A: Mathematical and Theoretical</i>. 2019;52(4). doi:<a href=\"https://doi.org/10.1088/1751-8121/aaf2dd\">10.1088/1751-8121/aaf2dd</a>","ieee":"D. De Martino, “Feedback-induced self-oscillations in large interacting systems subjected to phase transitions,” <i>Journal of Physics A: Mathematical and Theoretical</i>, vol. 52, no. 4. IOP Publishing, 2019.","apa":"De Martino, D. (2019). Feedback-induced self-oscillations in large interacting systems subjected to phase transitions. <i>Journal of Physics A: Mathematical and Theoretical</i>. IOP Publishing. <a href=\"https://doi.org/10.1088/1751-8121/aaf2dd\">https://doi.org/10.1088/1751-8121/aaf2dd</a>","mla":"De Martino, Daniele. “Feedback-Induced Self-Oscillations in Large Interacting Systems Subjected to Phase Transitions.” <i>Journal of Physics A: Mathematical and Theoretical</i>, vol. 52, no. 4, 045002, IOP Publishing, 2019, doi:<a href=\"https://doi.org/10.1088/1751-8121/aaf2dd\">10.1088/1751-8121/aaf2dd</a>."},"article_number":"045002","status":"public","publication":"Journal of Physics A: Mathematical and Theoretical","has_accepted_license":"1","scopus_import":"1","ec_funded":1,"publisher":"IOP Publishing","file":[{"date_updated":"2020-07-14T12:47:17Z","access_level":"open_access","date_created":"2019-04-19T12:18:57Z","content_type":"application/pdf","checksum":"1112304ad363a6d8afaeccece36473cf","file_size":1804557,"creator":"kschuh","file_name":"2019_IOP_DeMartino.pdf","relation":"main_file","file_id":"6344"}],"issue":"4","volume":52,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","day":"07","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"oa":1,"quality_controlled":"1","date_published":"2019-01-07T00:00:00Z","_id":"6049","isi":1,"publication_status":"published","intvolume":"        52","language":[{"iso":"eng"}],"article_processing_charge":"Yes (in subscription journal)","date_created":"2019-02-24T22:59:19Z","doi":"10.1088/1751-8121/aaf2dd","oa_version":"Published Version","title":"Feedback-induced self-oscillations in large interacting systems subjected to phase transitions","department":[{"_id":"GaTk"}],"corr_author":"1","project":[{"grant_number":"291734","name":"International IST Postdoc Fellowship Programme","_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"}],"external_id":{"isi":["000455379500001"]},"abstract":[{"text":"In this article it is shown that large systems with many interacting units endowing multiple phases display self-oscillations in the presence of linear feedback between the control and order parameters, where an Andronov–Hopf bifurcation takes over the phase transition. This is simply illustrated through the mean field Landau theory whose feedback dynamics turn out to be described by the Van der Pol equation and it is then validated for the fully connected Ising model following heat bath dynamics. Despite its simplicity, this theory accounts potentially for a rich range of phenomena: here it is applied to describe in a stylized way (i) excess demand-price cycles due to strong herding in a simple agent-based market model; (ii) congestion waves in queuing networks triggered by user feedback to delays in overloaded conditions; and (iii) metabolic network oscillations resulting from cell growth control in a bistable phenotypic landscape.","lang":"eng"}],"month":"01","file_date_updated":"2020-07-14T12:47:17Z","type":"journal_article"},{"external_id":{"isi":["000459916500007"]},"abstract":[{"lang":"eng","text":"Cells need to reliably sense external ligand concentrations to achieve various biological functions such as chemotaxis or signaling. The molecular recognition of ligands by surface receptors is degenerate in many systems, leading to crosstalk between ligand-receptor pairs. Crosstalk is often thought of as a deviation from optimal specific recognition, as the binding of noncognate ligands can interfere with the detection of the receptor's cognate ligand, possibly leading to a false triggering of a downstream signaling pathway. Here we quantify the optimal precision of sensing the concentrations of multiple ligands by a collection of promiscuous receptors. We demonstrate that crosstalk can improve precision in concentration sensing and discrimination tasks. To achieve superior precision, the additional information about ligand concentrations contained in short binding events of the noncognate ligand should be exploited. We present a proofreading scheme to realize an approximate estimation of multiple ligand concentrations that reaches a precision close to the derived optimal bounds. Our results help rationalize the observed ubiquity of receptor crosstalk in molecular sensing."}],"month":"02","type":"journal_article","article_processing_charge":"No","main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/448118v1.abstract"}],"oa_version":"Preprint","doi":"10.1103/PhysRevE.99.022423","date_created":"2019-03-10T22:59:20Z","title":"Receptor crosstalk improves concentration sensing of multiple ligands","department":[{"_id":"NiBa"},{"_id":"GaTk"}],"publication_status":"published","intvolume":"        99","language":[{"iso":"eng"}],"date_published":"2019-02-26T00:00:00Z","_id":"6090","isi":1,"oa":1,"quality_controlled":"1","issue":"2","volume":99,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","day":"26","citation":{"ama":"Carballo-Pacheco M, Desponds J, Gavrilchenko T, et al. Receptor crosstalk improves concentration sensing of multiple ligands. <i>Physical Review E</i>. 2019;99(2). doi:<a href=\"https://doi.org/10.1103/PhysRevE.99.022423\">10.1103/PhysRevE.99.022423</a>","mla":"Carballo-Pacheco, Martín, et al. “Receptor Crosstalk Improves Concentration Sensing of Multiple Ligands.” <i>Physical Review E</i>, vol. 99, no. 2, 022423, American Physical Society, 2019, doi:<a href=\"https://doi.org/10.1103/PhysRevE.99.022423\">10.1103/PhysRevE.99.022423</a>.","apa":"Carballo-Pacheco, M., Desponds, J., Gavrilchenko, T., Mayer, A., Prizak, R., Reddy, G., … Mora, T. (2019). Receptor crosstalk improves concentration sensing of multiple ligands. <i>Physical Review E</i>. American Physical Society. <a href=\"https://doi.org/10.1103/PhysRevE.99.022423\">https://doi.org/10.1103/PhysRevE.99.022423</a>","ieee":"M. Carballo-Pacheco <i>et al.</i>, “Receptor crosstalk improves concentration sensing of multiple ligands,” <i>Physical Review E</i>, vol. 99, no. 2. American Physical Society, 2019.","ista":"Carballo-Pacheco M, Desponds J, Gavrilchenko T, Mayer A, Prizak R, Reddy G, Nemenman I, Mora T. 2019. Receptor crosstalk improves concentration sensing of multiple ligands. Physical Review E. 99(2), 022423.","short":"M. Carballo-Pacheco, J. Desponds, T. Gavrilchenko, A. Mayer, R. Prizak, G. Reddy, I. Nemenman, T. Mora, Physical Review E 99 (2019).","chicago":"Carballo-Pacheco, Martín, Jonathan Desponds, Tatyana Gavrilchenko, Andreas Mayer, Roshan Prizak, Gautam Reddy, Ilya Nemenman, and Thierry Mora. “Receptor Crosstalk Improves Concentration Sensing of Multiple Ligands.” <i>Physical Review E</i>. American Physical Society, 2019. <a href=\"https://doi.org/10.1103/PhysRevE.99.022423\">https://doi.org/10.1103/PhysRevE.99.022423</a>."},"article_number":"022423","publication":"Physical Review E","status":"public","scopus_import":"1","publisher":"American Physical Society","date_updated":"2024-02-28T13:12:06Z","year":"2019","author":[{"full_name":"Carballo-Pacheco, Martín","first_name":"Martín","last_name":"Carballo-Pacheco"},{"last_name":"Desponds","first_name":"Jonathan","full_name":"Desponds, Jonathan"},{"full_name":"Gavrilchenko, Tatyana","last_name":"Gavrilchenko","first_name":"Tatyana"},{"first_name":"Andreas","last_name":"Mayer","full_name":"Mayer, Andreas"},{"full_name":"Prizak, Roshan","last_name":"Prizak","first_name":"Roshan","id":"4456104E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gautam","last_name":"Reddy","full_name":"Reddy, Gautam"},{"full_name":"Nemenman, Ilya","last_name":"Nemenman","first_name":"Ilya"},{"last_name":"Mora","first_name":"Thierry","full_name":"Mora, Thierry"}]},{"_id":"6784","related_material":{"record":[{"status":"public","relation":"research_data","id":"9786"}]},"isi":1,"date_published":"2019-07-02T00:00:00Z","language":[{"iso":"eng"}],"intvolume":"        15","publication_status":"published","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"title":"Molecular noise of innate immunity shapes bacteria-phage ecologies","doi":"10.1371/journal.pcbi.1007168","oa_version":"Published Version","date_created":"2019-08-11T21:59:19Z","article_processing_charge":"No","month":"07","type":"journal_article","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."}],"external_id":{"isi":["000481577700032"]},"project":[{"_id":"251D65D8-B435-11E9-9278-68D0E5697425","grant_number":"24210","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level"},{"_id":"251BCBEC-B435-11E9-9278-68D0E5697425","grant_number":"RGY0079/2011","name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems"}],"publication_identifier":{"eissn":["1553-7358"]},"author":[{"full_name":"Ruess, Jakob","first_name":"Jakob","last_name":"Ruess","id":"4A245D00-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1615-3282"},{"full_name":"Pleska, Maros","first_name":"Maros","last_name":"Pleska","orcid":"0000-0001-7460-7479","id":"4569785E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Tkačik","first_name":"Gašper","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"year":"2019","date_updated":"2025-04-14T13:46:26Z","file":[{"creator":"dernst","file_name":"2019_PlosComputBiology_Ruess.pdf","relation":"main_file","file_id":"6803","access_level":"open_access","date_updated":"2020-07-14T12:47:40Z","date_created":"2019-08-12T12:27:26Z","checksum":"7ded4721b41c2a0fc66a1c634540416a","file_size":2200003,"content_type":"application/pdf"}],"publisher":"Public Library of Science","scopus_import":"1","has_accepted_license":"1","publication":"PLoS Computational Biology","status":"public","ddc":["570"],"citation":{"ieee":"J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Molecular noise of innate immunity shapes bacteria-phage ecologies,” <i>PLoS Computational Biology</i>, vol. 15, no. 7. Public Library of Science, 2019.","mla":"Ruess, Jakob, et al. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” <i>PLoS Computational Biology</i>, vol. 15, no. 7, e1007168, Public Library of Science, 2019, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007168\">10.1371/journal.pcbi.1007168</a>.","ama":"Ruess J, Pleska M, Guet CC, Tkačik G. Molecular noise of innate immunity shapes bacteria-phage ecologies. <i>PLoS Computational Biology</i>. 2019;15(7). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007168\">10.1371/journal.pcbi.1007168</a>","apa":"Ruess, J., Pleska, M., Guet, C. C., &#38; Tkačik, G. (2019). Molecular noise of innate immunity shapes bacteria-phage ecologies. <i>PLoS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1007168\">https://doi.org/10.1371/journal.pcbi.1007168</a>","ista":"Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Molecular noise of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology. 15(7), e1007168.","chicago":"Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” <i>PLoS Computational Biology</i>. Public Library of Science, 2019. <a href=\"https://doi.org/10.1371/journal.pcbi.1007168\">https://doi.org/10.1371/journal.pcbi.1007168</a>.","short":"J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, PLoS Computational Biology 15 (2019)."},"article_number":"e1007168","day":"02","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","volume":15,"issue":"7","article_type":"original","quality_controlled":"1","oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"}},{"author":[{"full_name":"Wang, Jilin W. J. L.","last_name":"Wang","first_name":"Jilin W. J. L."},{"id":"A057D288-3E88-11E9-986D-0CF4E5697425","orcid":"0000-0003-2623-5249","full_name":"Lombardi, Fabrizio","first_name":"Fabrizio","last_name":"Lombardi"},{"full_name":"Zhang, Xiyun","first_name":"Xiyun","last_name":"Zhang"},{"first_name":"Christelle","last_name":"Anaclet","full_name":"Anaclet, Christelle"},{"full_name":"Ivanov, Plamen Ch.","last_name":"Ivanov","first_name":"Plamen Ch."}],"year":"2019","date_updated":"2025-04-14T07:44:06Z","file":[{"file_size":3982516,"content_type":"application/pdf","checksum":"2a096a9c6dcc6eaa94077b2603bc6c12","date_created":"2019-11-25T08:24:01Z","date_updated":"2020-07-14T12:47:49Z","access_level":"open_access","relation":"main_file","file_id":"7104","creator":"dernst","file_name":"2019_PLOSComBio_Wang.pdf"}],"publisher":"Public Library of Science","has_accepted_license":"1","ec_funded":1,"scopus_import":"1","status":"public","publication":"PLoS Computational Biology","ddc":["570","000"],"citation":{"apa":"Wang, J. W. J. L., Lombardi, F., Zhang, X., Anaclet, C., &#38; Ivanov, P. C. (2019). Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture. <i>PLoS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1007268\">https://doi.org/10.1371/journal.pcbi.1007268</a>","mla":"Wang, Jilin W. J. L., et al. “Non-Equilibrium Critical Dynamics of Bursts in θ and δ Rhythms as Fundamental Characteristic of Sleep and Wake Micro-Architecture.” <i>PLoS Computational Biology</i>, vol. 15, no. 11, e1007268, Public Library of Science, 2019, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007268\">10.1371/journal.pcbi.1007268</a>.","ieee":"J. W. J. L. Wang, F. Lombardi, X. Zhang, C. Anaclet, and P. C. Ivanov, “Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture,” <i>PLoS Computational Biology</i>, vol. 15, no. 11. Public Library of Science, 2019.","ama":"Wang JWJL, Lombardi F, Zhang X, Anaclet C, Ivanov PC. Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture. <i>PLoS Computational Biology</i>. 2019;15(11). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1007268\">10.1371/journal.pcbi.1007268</a>","chicago":"Wang, Jilin W. J. L., Fabrizio Lombardi, Xiyun Zhang, Christelle Anaclet, and Plamen Ch. Ivanov. “Non-Equilibrium Critical Dynamics of Bursts in θ and δ Rhythms as Fundamental Characteristic of Sleep and Wake Micro-Architecture.” <i>PLoS Computational Biology</i>. Public Library of Science, 2019. <a href=\"https://doi.org/10.1371/journal.pcbi.1007268\">https://doi.org/10.1371/journal.pcbi.1007268</a>.","short":"J.W.J.L. Wang, F. Lombardi, X. Zhang, C. Anaclet, P.C. Ivanov, PLoS Computational Biology 15 (2019).","ista":"Wang JWJL, Lombardi F, Zhang X, Anaclet C, Ivanov PC. 2019. Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture. PLoS Computational Biology. 15(11), e1007268."},"article_number":"e1007268","day":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","volume":15,"issue":"11","article_type":"original","quality_controlled":"1","oa":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"_id":"7103","isi":1,"date_published":"2019-11-01T00:00:00Z","language":[{"iso":"eng"}],"intvolume":"        15","publication_status":"published","pmid":1,"department":[{"_id":"GaTk"}],"title":"Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture","doi":"10.1371/journal.pcbi.1007268","date_created":"2019-11-25T08:20:47Z","oa_version":"Published Version","article_processing_charge":"No","month":"11","file_date_updated":"2020-07-14T12:47:49Z","type":"journal_article","abstract":[{"text":"Origin and functions of intermittent transitions among sleep stages, including short awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing the sleep-wake cycle results from an underlying non-equilibrium critical dynamics, bridging collective behaviors across spatio-temporal scales. We investigate θ and δ wave dynamics in control rats and in rats with lesions of sleep-promoting neurons in the parafacial zone. We demonstrate that intermittent bursts in θ and δ rhythms exhibit a complex temporal organization, with long-range power-law correlations and a robust duality of power law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, typical features of non-equilibrium systems self-organizing at criticality. Crucially, such temporal organization relates to anti-correlated coupling between θ- and δ-bursts, and is independent of the dominant physiologic state and lesions, a solid indication of a basic principle in sleep dynamics.","lang":"eng"}],"external_id":{"isi":["000500976100014"],"pmid":["31725712"]},"project":[{"call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"}],"publication_identifier":{"issn":["1553-7358"]}},{"issue":"5","volume":150,"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","day":"07","oa":1,"quality_controlled":"1","article_type":"original","date_updated":"2023-09-06T14:59:28Z","year":"2019","author":[{"first_name":"Thomas R","last_name":"Sokolowski","full_name":"Sokolowski, Thomas R","id":"3E999752-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1287-3779"},{"first_name":"Joris","last_name":"Paijmans","full_name":"Paijmans, Joris"},{"last_name":"Bossen","first_name":"Laurens","full_name":"Bossen, Laurens"},{"full_name":"Miedema, Thomas","first_name":"Thomas","last_name":"Miedema"},{"first_name":"Martijn","last_name":"Wehrens","full_name":"Wehrens, Martijn"},{"full_name":"Becker, Nils B.","first_name":"Nils B.","last_name":"Becker"},{"full_name":"Kaizu, Kazunari","first_name":"Kazunari","last_name":"Kaizu"},{"first_name":"Koichi","last_name":"Takahashi","full_name":"Takahashi, Koichi"},{"full_name":"Dogterom, Marileen","first_name":"Marileen","last_name":"Dogterom"},{"first_name":"Pieter Rein","last_name":"ten Wolde","full_name":"ten Wolde, Pieter Rein"}],"citation":{"apa":"Sokolowski, T. R., Paijmans, J., Bossen, L., Miedema, T., Wehrens, M., Becker, N. B., … ten Wolde, P. R. (2019). eGFRD in all dimensions. <i>The Journal of Chemical Physics</i>. AIP Publishing. <a href=\"https://doi.org/10.1063/1.5064867\">https://doi.org/10.1063/1.5064867</a>","ama":"Sokolowski TR, Paijmans J, Bossen L, et al. eGFRD in all dimensions. <i>The Journal of Chemical Physics</i>. 2019;150(5). doi:<a href=\"https://doi.org/10.1063/1.5064867\">10.1063/1.5064867</a>","ieee":"T. R. Sokolowski <i>et al.</i>, “eGFRD in all dimensions,” <i>The Journal of Chemical Physics</i>, vol. 150, no. 5. AIP Publishing, 2019.","mla":"Sokolowski, Thomas R., et al. “EGFRD in All Dimensions.” <i>The Journal of Chemical Physics</i>, vol. 150, no. 5, 054108, AIP Publishing, 2019, doi:<a href=\"https://doi.org/10.1063/1.5064867\">10.1063/1.5064867</a>.","chicago":"Sokolowski, Thomas R, Joris Paijmans, Laurens Bossen, Thomas Miedema, Martijn Wehrens, Nils B. Becker, Kazunari Kaizu, Koichi Takahashi, Marileen Dogterom, and Pieter Rein ten Wolde. “EGFRD in All Dimensions.” <i>The Journal of Chemical Physics</i>. AIP Publishing, 2019. <a href=\"https://doi.org/10.1063/1.5064867\">https://doi.org/10.1063/1.5064867</a>.","short":"T.R. Sokolowski, J. Paijmans, L. Bossen, T. Miedema, M. Wehrens, N.B. Becker, K. Kaizu, K. Takahashi, M. Dogterom, P.R. ten Wolde, The Journal of Chemical Physics 150 (2019).","ista":"Sokolowski TR, Paijmans J, Bossen L, Miedema T, Wehrens M, Becker NB, Kaizu K, Takahashi K, Dogterom M, ten Wolde PR. 2019. eGFRD in all dimensions. The Journal of Chemical Physics. 150(5), 054108."},"article_number":"054108","publication":"The Journal of Chemical Physics","status":"public","publisher":"AIP Publishing","main_file_link":[{"url":"https://arxiv.org/abs/1708.09364","open_access":"1"}],"article_processing_charge":"No","doi":"10.1063/1.5064867","oa_version":"Preprint","date_created":"2020-01-30T10:34:36Z","title":"eGFRD in all dimensions","department":[{"_id":"GaTk"}],"publication_identifier":{"eissn":["1089-7690"],"issn":["0021-9606"]},"external_id":{"isi":["000458109300009"],"arxiv":["1708.09364"]},"abstract":[{"text":"Biochemical reactions often occur at low copy numbers but at once in crowded and diverse environments. Space and stochasticity therefore play an essential role in biochemical networks. Spatial-stochastic simulations have become a prominent tool for understanding how stochasticity at the microscopic level influences the macroscopic behavior of such systems. While particle-based models guarantee the level of detail necessary to accurately describe the microscopic dynamics at very low copy numbers, the algorithms used to simulate them typically imply trade-offs between computational efficiency and biochemical accuracy. eGFRD (enhanced Green’s Function Reaction Dynamics) is an exact algorithm that evades such trade-offs by partitioning the N-particle system into M ≤ N analytically tractable one- and two-particle systems; the analytical solutions (Green’s functions) then are used to implement an event-driven particle-based scheme that allows particles to make large jumps in time and space while retaining access to their state variables at arbitrary simulation times. Here we present “eGFRD2,” a new eGFRD version that implements the principle of eGFRD in all dimensions, thus enabling efficient particle-based simulation of biochemical reaction-diffusion processes in the 3D cytoplasm, on 2D planes representing membranes, and on 1D elongated cylinders representative of, e.g., cytoskeletal tracks or DNA; in 1D, it also incorporates convective motion used to model active transport. We find that, for low particle densities, eGFRD2 is up to 6 orders of magnitude faster than conventional Brownian dynamics. We exemplify the capabilities of eGFRD2 by simulating an idealized model of Pom1 gradient formation, which involves 3D diffusion, active transport on microtubules, and autophosphorylation on the membrane, confirming recent experimental and theoretical results on this system to hold under genuinely stochastic conditions.","lang":"eng"}],"type":"journal_article","arxiv":1,"month":"02","date_published":"2019-02-07T00:00:00Z","isi":1,"_id":"7422","publication_status":"published","intvolume":"       150","language":[{"iso":"eng"}]}]