[{"year":"2026","quality_controlled":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","PlanS_conform":"1","month":"05","department":[{"_id":"GradSch"},{"_id":"CaGu"},{"_id":"GaTk"}],"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_number":"102483","article_type":"original","publication_status":"published","oa_version":"Published Version","external_id":{"arxiv":["2601.19681"]},"main_file_link":[{"url":"https://doi.org/10.1016/j.gde.2026.102483","open_access":"1"}],"author":[{"orcid":"0000-0003-2977-7844","last_name":"Mascolo","full_name":"Mascolo, Elia","first_name":"Elia","id":"776a6ed0-a053-11f0-8635-80b95e0e0d53"},{"first_name":"Reka E","id":"50FDE43E-AA30-11E9-A72B-8A12E6697425","full_name":"Körei, Reka E","last_name":"Körei"},{"full_name":"Herrera-Álvarez, Santiago","first_name":"Santiago","last_name":"Herrera-Álvarez"},{"full_name":"Guet, Calin C","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet"},{"first_name":"Justin","full_name":"Crocker, Justin","last_name":"Crocker"},{"full_name":"Tkačik, Gašper","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik","orcid":"0000-0002-6699-1455"}],"arxiv":1,"intvolume":"        99","title":"Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps","has_accepted_license":"1","ddc":["570"],"OA_place":"publisher","OA_type":"hybrid","type":"journal_article","scopus_import":"1","publication":"Current Opinion in Genetics & Development","date_published":"2026-05-09T00:00:00Z","corr_author":"1","date_created":"2026-06-10T07:37:12Z","oa":1,"day":"09","publisher":"Elsevier","_id":"21983","acknowledgement":"We thank Nick Barton and Noa Ottilie Borst for essential contributions to this manuscript.\r\nE.M. acknowledges support from the APART-USA fellowship, jointly funded by the Austrian Academy of Sciences (ÖAW) and the Institute of Science and Technology Austria (ISTA).\r\nThis study was supported by the European Molecular Biology Laboratory (J.C.); the European Molecular Biology Laboratory Interdisciplinary Postdoc Programme (EIPOD) under the Marie Skłodowska-Curie Actions cofund (S.H.A.).","status":"public","article_processing_charge":"Yes (via OA deal)","volume":99,"language":[{"iso":"eng"}],"citation":{"ieee":"E. Mascolo, R. E. Körei, S. Herrera-Álvarez, C. C. Guet, J. Crocker, and G. Tkačik, “Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps,” <i>Current Opinion in Genetics &#38; Development</i>, vol. 99. Elsevier, 2026.","ama":"Mascolo E, Körei RE, Herrera-Álvarez S, Guet CC, Crocker J, Tkačik G. Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps. <i>Current Opinion in Genetics &#38; Development</i>. 2026;99. doi:<a href=\"https://doi.org/10.1016/j.gde.2026.102483\">10.1016/j.gde.2026.102483</a>","ista":"Mascolo E, Körei RE, Herrera-Álvarez S, Guet CC, Crocker J, Tkačik G. 2026. Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps. Current Opinion in Genetics &#38; Development. 99, 102483.","chicago":"Mascolo, Elia, Reka E Körei, Santiago Herrera-Álvarez, Calin C Guet, Justin Crocker, and Gašper Tkačik. “Long-Term Evolution of Regulatory DNA Sequences. Part 1: Simulations on Global, Biophysically-Realistic Genotype–Phenotype Maps.” <i>Current Opinion in Genetics &#38; Development</i>. Elsevier, 2026. <a href=\"https://doi.org/10.1016/j.gde.2026.102483\">https://doi.org/10.1016/j.gde.2026.102483</a>.","apa":"Mascolo, E., Körei, R. E., Herrera-Álvarez, S., Guet, C. C., Crocker, J., &#38; Tkačik, G. (2026). Long-term evolution of regulatory DNA sequences. Part 1: Simulations on global, biophysically-realistic genotype–phenotype maps. <i>Current Opinion in Genetics &#38; Development</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.gde.2026.102483\">https://doi.org/10.1016/j.gde.2026.102483</a>","short":"E. Mascolo, R.E. Körei, S. Herrera-Álvarez, C.C. Guet, J. Crocker, G. Tkačik, Current Opinion in Genetics &#38; Development 99 (2026).","mla":"Mascolo, Elia, et al. “Long-Term Evolution of Regulatory DNA Sequences. Part 1: Simulations on Global, Biophysically-Realistic Genotype–Phenotype Maps.” <i>Current Opinion in Genetics &#38; Development</i>, vol. 99, 102483, Elsevier, 2026, doi:<a href=\"https://doi.org/10.1016/j.gde.2026.102483\">10.1016/j.gde.2026.102483</a>."},"doi":"10.1016/j.gde.2026.102483","abstract":[{"text":"Promoters and enhancers are cis-regulatory elements (CREs), DNA sequences that bind transcription factor (TF) proteins to up- or down-regulate target genes. Decades-long efforts yielded TF-DNA interaction models that predict how strongly an individual TF binds arbitrary DNA sequences and how individual binding events on the CRE combine to affect gene expression. These insights can be synthesized into a global, biophysically realistic, and quantitative genotype–phenotype map for gene regulation, a ‘holy grail’ for the application of evolutionary theory. A global map provides a rare opportunity to simulate the long-term evolution of regulatory sequences and pose several fundamental questions: How long does it take to evolve CREs de novo? How many non-trivial regulatory functions exist in sequence space? How connected are they? For which regulatory architecture is CRE evolution most rapid and evolvable? In this article, the first of a two-part series, we briefly review the pertinent modeling and simulation efforts for a unique system that enables close, quantitative, and mechanistic links between biophysics, as well as systems, synthetic, and evolutionary biology.","lang":"eng"}],"date_updated":"2026-06-16T12:37:02Z","publication_identifier":{"eissn":["1879-0380"],"issn":["0959-437X"]}},{"department":[{"_id":"GaTk"}],"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_number":"017001","article_type":"original","year":"2026","quality_controlled":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","PlanS_conform":"1","month":"01","external_id":{"arxiv":["2510.24536"]},"author":[{"id":"e1e86031-6537-11eb-953a-f7ab92be508d","first_name":"David","full_name":"Brückner, David","last_name":"Brückner","orcid":"0000-0001-7205-2975"},{"full_name":"Tkačik, Gašper","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","last_name":"Tkačik"}],"arxiv":1,"intvolume":"         4","project":[{"grant_number":"101118866","name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos","_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9"}],"publication_status":"published","file":[{"date_updated":"2026-02-24T06:57:44Z","content_type":"application/pdf","file_name":"2026_PRXLife_Brueckner.pdf","checksum":"99ef02dd741c4536eeefd12d409d5269","date_created":"2026-02-24T06:57:44Z","file_id":"21352","access_level":"open_access","creator":"dernst","success":1,"file_size":1147994,"relation":"main_file"}],"oa_version":"Published Version","type":"journal_article","publication":"PRX Life","date_published":"2026-01-23T00:00:00Z","has_accepted_license":"1","DOAJ_listed":"1","title":"Marr's three levels for embryonic development: Information, dynamical systems, gene networks","ddc":["570"],"OA_place":"publisher","OA_type":"gold","language":[{"iso":"eng"}],"volume":4,"doi":"10.1103/fdcf-dkws","citation":{"short":"D. Brückner, G. Tkačik, PRX Life 4 (2026).","mla":"Brückner, David, and Gašper Tkačik. “Marr’s Three Levels for Embryonic Development: Information, Dynamical Systems, Gene Networks.” <i>PRX Life</i>, vol. 4, 017001, American Physical Society, 2026, doi:<a href=\"https://doi.org/10.1103/fdcf-dkws\">10.1103/fdcf-dkws</a>.","ieee":"D. Brückner and G. Tkačik, “Marr’s three levels for embryonic development: Information, dynamical systems, gene networks,” <i>PRX Life</i>, vol. 4. American Physical Society, 2026.","chicago":"Brückner, David, and Gašper Tkačik. “Marr’s Three Levels for Embryonic Development: Information, Dynamical Systems, Gene Networks.” <i>PRX Life</i>. American Physical Society, 2026. <a href=\"https://doi.org/10.1103/fdcf-dkws\">https://doi.org/10.1103/fdcf-dkws</a>.","apa":"Brückner, D., &#38; Tkačik, G. (2026). Marr’s three levels for embryonic development: Information, dynamical systems, gene networks. <i>PRX Life</i>. American Physical Society. <a href=\"https://doi.org/10.1103/fdcf-dkws\">https://doi.org/10.1103/fdcf-dkws</a>","ama":"Brückner D, Tkačik G. Marr’s three levels for embryonic development: Information, dynamical systems, gene networks. <i>PRX Life</i>. 2026;4. doi:<a href=\"https://doi.org/10.1103/fdcf-dkws\">10.1103/fdcf-dkws</a>","ista":"Brückner D, Tkačik G. 2026. Marr’s three levels for embryonic development: Information, dynamical systems, gene networks. PRX Life. 4, 017001."},"file_date_updated":"2026-02-24T06:57:44Z","abstract":[{"text":"Developmental patterning comprises processes that range from purely instructed, where external signals specify cell fates, to fully self-organized, where spatial patterns emerge autonomously through cellular interactions. We propose that both extremes—as well as the continuum of intermediate cases—can be conceptualized as information-processing systems, whose operation can be described using “Marr's three levels of analysis”: the computational problem being solved, the algorithms employed, and their molecular implementation. At the first level, we argue that normative theories, such as information-theoretic optimization principles, provide a formalization of the computational problem. At the second level, we show how simplified information-processing architectures provide a framework for developmental algorithms, which are formalized mathematically using dynamical systems theory. At the third level, the implementation of developmental algorithms is described by mechanistic biophysical and gene regulatory network models.","lang":"eng"}],"date_updated":"2026-02-24T07:00:16Z","publication_identifier":{"eissn":["2835-8279"]},"corr_author":"1","oa":1,"date_created":"2026-02-17T08:29:10Z","day":"23","publisher":"American Physical Society","_id":"21282","acknowledgement":"We thank Edouard Hannezo, Anna Kicheva, Fridtjof Brauns, and all members of the Brückner and Tkačik groups for feedback and inspiring discussions. This work was supported in part by European Research Council ERC-2023-SyG “Dynatrans” Grant No. 101118866 (G.T.). This work was conducted while visiting the Okinawa Institute of Science and Technology (OIST) through the Theoretical Sciences Visiting Program (TSVP); at the Kavli Institute for Theoretical Physics (KITP) Santa Barbara, supported by NSF Grant No. PHY-1748958 and the Gordon and Betty Moore Foundation Grant No. 2919.02; and at Lucullus, Vienna.","status":"public","article_processing_charge":"Yes"},{"abstract":[{"text":"In many developmental systems, cells differentiate into a tissue by reading out morphogen concentration fields, a process fundamentally limited by noise. How much can the precision of this process be improved by nonlocal information, e.g., via cell-cell communication? Using a Bayes-optimal framework, we show that positional inference depends crucially on morphogen spatial correlations and on the \"structural prior\" that encodes the geometry of the cellular lattice performing the readout, thereby determining what a cell can reliably assume about the position of its neighbors when interpreting nonlocal morphogen signals. We derive upper bounds on positional information gain due to nonlocal readout and identify signal processing algorithms that approximate optimal positional inference, as well as simple chemical reaction schemes which implement such algorithms. Our theory suggests that correlational information can be exploited to significantly enhance developmental precision.","lang":"eng"}],"date_updated":"2026-07-16T09:58:04Z","publication_identifier":{"eissn":[" 1079-7114"],"issn":["0031-9007"]},"language":[{"iso":"eng"}],"volume":137,"citation":{"short":"C.Y. Zhang, P. Mateu Hoyos, D. Brückner, G. Tkačik, Physical Review Letters 137 (2026).","mla":"Zhang, Chen Y., et al. “Nonlocal Decoding of Positional and Correlational Information during Development.” <i>Physical Review Letters</i>, vol. 137, 038401, American Physical Society, 2026, doi:<a href=\"https://doi.org/10.1103/mbjk-v4ym\">10.1103/mbjk-v4ym</a>.","ieee":"C. Y. Zhang, P. Mateu Hoyos, D. Brückner, and G. Tkačik, “Nonlocal decoding of positional and correlational information during development,” <i>Physical Review Letters</i>, vol. 137. American Physical Society, 2026.","chicago":"Zhang, Chen Y, Pablo Mateu Hoyos, David Brückner, and Gašper Tkačik. “Nonlocal Decoding of Positional and Correlational Information during Development.” <i>Physical Review Letters</i>. American Physical Society, 2026. <a href=\"https://doi.org/10.1103/mbjk-v4ym\">https://doi.org/10.1103/mbjk-v4ym</a>.","apa":"Zhang, C. Y., Mateu Hoyos, P., Brückner, D., &#38; Tkačik, G. (2026). Nonlocal decoding of positional and correlational information during development. <i>Physical Review Letters</i>. American Physical Society. <a href=\"https://doi.org/10.1103/mbjk-v4ym\">https://doi.org/10.1103/mbjk-v4ym</a>","ama":"Zhang CY, Mateu Hoyos P, Brückner D, Tkačik G. Nonlocal decoding of positional and correlational information during development. <i>Physical Review Letters</i>. 2026;137. doi:<a href=\"https://doi.org/10.1103/mbjk-v4ym\">10.1103/mbjk-v4ym</a>","ista":"Zhang CY, Mateu Hoyos P, Brückner D, Tkačik G. 2026. Nonlocal decoding of positional and correlational information during development. Physical Review Letters. 137, 038401."},"doi":"10.1103/mbjk-v4ym","file_date_updated":"2026-07-16T09:54:55Z","acknowledgement":"This work was supported in part\r\nby European Research Council No. ERC-2023-SyG\r\n“DynaTrans” Grant No. 101118866 (G. T.). We thank\r\nPieter Rein ten Wolde and Vahe Galstyan for stimulating\r\ndiscussions.","status":"public","article_processing_charge":"Yes (via OA deal)","corr_author":"1","date_created":"2026-07-14T05:38:28Z","oa":1,"publisher":"American Physical Society","day":"15","_id":"22326","publication":"Physical Review Letters","date_published":"2026-07-15T00:00:00Z","das_tickbox":"1","type":"journal_article","scopus_import":"1","researchdata_availability":"no","OA_type":"hybrid","title":"Nonlocal decoding of positional and correlational information during development","has_accepted_license":"1","ddc":["530"],"OA_place":"publisher","intvolume":"       137","project":[{"_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9","name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos","grant_number":"101118866"}],"author":[{"last_name":"Zhang","full_name":"Zhang, Chen Y","first_name":"Chen Y","id":"81b43fb8-c9d5-11ef-bf68-ade532a1f204"},{"full_name":"Mateu Hoyos, Pablo","id":"50b236c7-50c1-11ef-bb9a-a2375694f8b5","first_name":"Pablo","last_name":"Mateu Hoyos"},{"last_name":"Brückner","orcid":"0000-0001-7205-2975","full_name":"Brückner, David","first_name":"David","id":"e1e86031-6537-11eb-953a-f7ab92be508d"},{"last_name":"Tkačik","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"file":[{"date_created":"2026-07-16T09:54:55Z","file_name":"2026_PhysicalReviewLetters_Zhang.pdf","checksum":"28861d31d0f6cf541aaca04faaed1767","relation":"main_file","file_size":2550345,"success":1,"creator":"dernst","file_id":"22352","access_level":"open_access","content_type":"application/pdf","date_updated":"2026-07-16T09:54:55Z"}],"oa_version":"Published Version","supplementarymaterial":"no","publication_status":"published","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_number":"038401","article_type":"original","department":[{"_id":"GaTk"},{"_id":"EdHa"},{"_id":"GradSch"}],"dataavailabilitystatement":"Code to evaluate PI, to run algorithmic implementations of ALP and RLP decoding, and to\r\nperform simulations is publicly available at https://github.com/alex-chenyi-zhang/nonlocdec_pici.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","PlanS_conform":"1","month":"07","year":"2026","quality_controlled":"1"},{"abstract":[{"text":"Promoters and enhancers are cis-regulatory elements (CREs), DNA sequences that bind transcription factor (TF) proteins to up- or down-regulate target genes. Decades-long efforts yielded TF-DNA interaction models that predict how strongly an individual TF binds arbitrary DNA sequences and how individual binding events on the CRE combine to affect gene expression. These insights can be synthesized into a global, biophysically realistic, and quantitative genotype-phenotype (GP) map for gene regulation, a ‘holy grail’ for the application of evolutionary theory. A global map provides a rare opportunity to simulate the long-term evolution of regulatory sequences and pose several fundamental questions: How long does it take to evolve CREs de novo? How many non-trivial regulatory functions exist in sequence space? How connected are they? For which regulatory architecture is CRE evolution most rapid and evolvable? In this article, the second of a two-part series, we review the application of evolutionary concepts — epistasis, robustness, evolvability, tunability, plasticity, and bet-hedging — to the evolution of gene regulatory sequences. We then evaluate the potential for a unifying theory for the evolution of regulatory sequences and identify key open challenges.","lang":"eng"}],"date_updated":"2026-07-27T13:40:24Z","publication_identifier":{"eissn":["1879-0380"],"issn":["0959-437X"]},"language":[{"iso":"eng"}],"volume":98,"citation":{"ieee":"E. Mascolo, R. E. Körei, N. O. Borst, N. H. Barton, J. Crocker, and G. Tkačik, “Long-term evolution of regulatory DNA sequences. Part 2: Theory and future challenges,” <i>Current Opinion in Genetics and Development</i>, vol. 98. Elsevier, 2026.","ista":"Mascolo E, Körei RE, Borst NO, Barton NH, Crocker J, Tkačik G. 2026. Long-term evolution of regulatory DNA sequences. Part 2: Theory and future challenges. Current Opinion in Genetics and Development. 98, 102472.","ama":"Mascolo E, Körei RE, Borst NO, Barton NH, Crocker J, Tkačik G. Long-term evolution of regulatory DNA sequences. Part 2: Theory and future challenges. <i>Current Opinion in Genetics and Development</i>. 2026;98. doi:<a href=\"https://doi.org/10.1016/j.gde.2026.102472\">10.1016/j.gde.2026.102472</a>","apa":"Mascolo, E., Körei, R. E., Borst, N. O., Barton, N. H., Crocker, J., &#38; Tkačik, G. (2026). Long-term evolution of regulatory DNA sequences. Part 2: Theory and future challenges. <i>Current Opinion in Genetics and Development</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.gde.2026.102472\">https://doi.org/10.1016/j.gde.2026.102472</a>","chicago":"Mascolo, Elia, Reka E Körei, Noa O. Borst, Nicholas H Barton, Justin Crocker, and Gašper Tkačik. “Long-Term Evolution of Regulatory DNA Sequences. Part 2: Theory and Future Challenges.” <i>Current Opinion in Genetics and Development</i>. Elsevier, 2026. <a href=\"https://doi.org/10.1016/j.gde.2026.102472\">https://doi.org/10.1016/j.gde.2026.102472</a>.","short":"E. Mascolo, R.E. Körei, N.O. Borst, N.H. Barton, J. Crocker, G. Tkačik, Current Opinion in Genetics and Development 98 (2026).","mla":"Mascolo, Elia, et al. “Long-Term Evolution of Regulatory DNA Sequences. Part 2: Theory and Future Challenges.” <i>Current Opinion in Genetics and Development</i>, vol. 98, 102472, Elsevier, 2026, doi:<a href=\"https://doi.org/10.1016/j.gde.2026.102472\">10.1016/j.gde.2026.102472</a>."},"doi":"10.1016/j.gde.2026.102472","file_date_updated":"2026-07-27T13:39:59Z","acknowledgement":"We thank Calin Guet and Santiago Herrera-Álvarez for essential contributions to this manuscript.\r\nE.M. acknowledges support from the APART-USA fellowship, jointly funded by the Austrian Academy of Sciences (ÖAW) and the Institute of Science and Technology Austria (ISTA). N.B. acknowledges funding from the ERC Advanced Grant 101055327 “HaplotypeStructure”.\r\nThis study was also supported by the European Molecular Biology Laboratory (N.O.B., J.C.).","status":"public","article_processing_charge":"Yes (via OA deal)","corr_author":"1","date_created":"2026-04-26T22:01:46Z","oa":1,"day":"01","publisher":"Elsevier","_id":"21759","publication":"Current Opinion in Genetics and Development","date_published":"2026-06-01T00:00:00Z","das_tickbox":"1","type":"journal_article","scopus_import":"1","researchdata_availability":"no","OA_type":"hybrid","has_accepted_license":"1","title":"Long-term evolution of regulatory DNA sequences. Part 2: Theory and future challenges","ddc":["570"],"OA_place":"publisher","intvolume":"        98","project":[{"name":"Understanding the evolution of continuous genomes","_id":"bd6958e0-d553-11ed-ba76-86eba6a76c00","grant_number":"101055327"}],"author":[{"first_name":"Elia","id":"776a6ed0-a053-11f0-8635-80b95e0e0d53","full_name":"Mascolo, Elia","last_name":"Mascolo","orcid":"0000-0003-2977-7844"},{"last_name":"Körei","full_name":"Körei, Reka E","first_name":"Reka E","id":"50FDE43E-AA30-11E9-A72B-8A12E6697425"},{"first_name":"Noa O.","full_name":"Borst, Noa O.","last_name":"Borst"},{"id":"4880FE40-F248-11E8-B48F-1D18A9856A87","first_name":"Nicholas H","full_name":"Barton, Nicholas H","last_name":"Barton","orcid":"0000-0002-8548-5240"},{"first_name":"Justin","full_name":"Crocker, Justin","last_name":"Crocker"},{"last_name":"Tkačik","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"file":[{"creator":"dernst","file_id":"22590","access_level":"open_access","relation":"main_file","file_size":3190001,"success":1,"date_created":"2026-07-27T13:39:59Z","checksum":"ac8bbee61717bfe7116e312cc6825259","file_name":"2026_CurrentOpinionGeneticsDev_Mascolo.pdf","date_updated":"2026-07-27T13:39:59Z","content_type":"application/pdf"}],"oa_version":"Published Version","supplementarymaterial":"no","publication_status":"published","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_type":"review","article_number":"102472","department":[{"_id":"GaTk"},{"_id":"NiBa"}],"dataavailabilitystatement":"No data were used for the research described in the article.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","PlanS_conform":"1","month":"06","year":"2026","quality_controlled":"1"},{"publication_identifier":{"issn":["2791-4585"]},"abstract":[{"lang":"eng","text":"Gaining an understanding of how biological regulation evolves is a fundamental research \r\nquestion in both evolutionary biology and molecular genetics. In order to gain more insight \r\ninto this topic, we focus on studying the simple gene regulatory system of the lac operon in \r\nE. coli. We show that simple population genetic models can shed light on evolution \r\nexperiments and that this combined approach of modelling the experimental system gives \r\ninsight to better understand the causes of evolutionary change in the experiment. We also \r\nstudy the natural diversity in the lac operon from 308 publicly available E. coli genomes that \r\ncome from various host species and different regions of the world. Evidence that selection is \r\ngenerally maintaining the function of the lac operon across the sample regardless of host \r\nspecies is provided and we show that different protein coding genes in the operon are under \r\ndifferent selective constraints on protein sequence preservation. A similar frameshift \r\nmutation found in experimental evolution studies is shown to be present in the sample we \r\nanalyzed, indicating that selectively relevant variants in evolution experiments are also \r\npresent in natural populations. We show that there is no simple phylogenetic relationship \r\nbetween host species, geographical location and the lac operon sequence. Finally, we argue \r\nthat a combined approach of comparative genomics, experimental evolution and theoretical \r\nmodelling contributes to a more complete understanding of molecular evolution. "}],"date_updated":"2026-07-31T10:52:08Z","file_date_updated":"2026-07-27T13:07:23Z","doi":"10.15479/AT-ISTA-22399","citation":{"mla":"Spasić, Aleksa. <i>Studying the Evolutionary Systems Biology of the Lac Operon</i>. Institute of Science and Technology Austria, 2026, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22399\">10.15479/AT-ISTA-22399</a>.","short":"A. Spasić, Studying the Evolutionary Systems Biology of the Lac Operon, Institute of Science and Technology Austria, 2026.","chicago":"Spasić, Aleksa. “Studying the Evolutionary Systems Biology of the Lac Operon.” Institute of Science and Technology Austria, 2026. <a href=\"https://doi.org/10.15479/AT-ISTA-22399\">https://doi.org/10.15479/AT-ISTA-22399</a>.","apa":"Spasić, A. (2026). <i>Studying the evolutionary systems biology of the lac operon</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-22399\">https://doi.org/10.15479/AT-ISTA-22399</a>","ama":"Spasić A. Studying the evolutionary systems biology of the lac operon. 2026. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-22399\">10.15479/AT-ISTA-22399</a>","ista":"Spasić A. 2026. Studying the evolutionary systems biology of the lac operon. Institute of Science and Technology Austria.","ieee":"A. Spasić, “Studying the evolutionary systems biology of the lac operon,” Institute of Science and Technology Austria, 2026."},"language":[{"iso":"eng"}],"status":"public","article_processing_charge":"No","publisher":"Institute of Science and Technology Austria","day":"27","_id":"22399","corr_author":"1","date_created":"2026-07-25T13:08:32Z","oa":1,"date_published":"2026-07-27T00:00:00Z","das_tickbox":"0","type":"dissertation","ddc":["576"],"OA_place":"publisher","has_accepted_license":"1","title":"Studying the evolutionary systems biology of the lac operon","author":[{"last_name":"Spasić","full_name":"Spasić, Aleksa","first_name":"Aleksa","id":"ecee9d38-4040-11ef-8843-b941efb445d6"}],"oa_version":"Published Version","file":[{"date_updated":"2026-07-27T13:00:07Z","content_type":"application/pdf","file_name":"Aleksa_Spasic_Thesis_final.pdf","checksum":"c29880dd71fcc37f23ac6e2843066ede","date_created":"2026-07-27T13:00:07Z","file_id":"22588","access_level":"open_access","creator":"aspasic","success":1,"relation":"main_file","file_size":1986078},{"date_created":"2026-07-27T13:00:22Z","checksum":"4ebe3bd2d833d913c0756343cca5e5f0","file_name":"Thesis_final.docx","creator":"aspasic","access_level":"closed","file_id":"22589","relation":"source_file","file_size":1868853,"date_updated":"2026-07-27T13:07:23Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document"}],"degree_awarded":"MS","publication_status":"published","page":"32","supervisor":[{"full_name":"Guet, Calin C","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet"},{"full_name":"Tkačik, Gašper","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","last_name":"Tkačik"}],"doi_confirm":"1","alternative_title":["ISTA Master’s Thesis"],"department":[{"_id":"GradSch"},{"_id":"GaTk"},{"_id":"CaGu"}],"month":"07","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","year":"2026"},{"_id":"22363","day":"14","publisher":"National Academy of Sciences","oa":1,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","date_created":"2026-07-19T22:01:46Z","corr_author":"1","article_processing_charge":"Yes","status":"public","acknowledgement":"This work was supported by the French NationalResearch Agency (ANR-20-CE12-0028 “ChroDynE” and ANR-23-CE13-0021“GastruCyp” and ANR-10 LABX-73 “Revive;” all T.G.), and by funding from theEuropean Research Council (ERC-2023-SyG, “Dynatrans,” 101118866, T.G. andG.T.). This work was also supported in part by the U.S. NSF, through the Centerfor the Physics of Biological Function (PHY-1734030, T.G.), and by NIH GrantsR01GM097275, U01DA047730, and U01DK127429 (T.G.)","file_date_updated":"2026-07-20T13:12:47Z","doi":"10.1073/pnas.2524855123","citation":{"short":"B. Zoller, A. Benichou, T. Gregor, G. Tkačik, Proceedings of the National Academy of Sciences of the United States of America 123 (2026).","mla":"Zoller, Benjamin, et al. “Invariant Nonequilibrium Dynamics in Gene Regulation Optimize Information Flow.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 123, no. 28, e2524855123, National Academy of Sciences, 2026, doi:<a href=\"https://doi.org/10.1073/pnas.2524855123\">10.1073/pnas.2524855123</a>.","ieee":"B. Zoller, A. Benichou, T. Gregor, and G. Tkačik, “Invariant nonequilibrium dynamics in gene regulation optimize information flow,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 123, no. 28. National Academy of Sciences, 2026.","apa":"Zoller, B., Benichou, A., Gregor, T., &#38; Tkačik, G. (2026). Invariant nonequilibrium dynamics in gene regulation optimize information flow. <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.2524855123\">https://doi.org/10.1073/pnas.2524855123</a>","chicago":"Zoller, Benjamin, Alexis Benichou, Thomas Gregor, and Gašper Tkačik. “Invariant Nonequilibrium Dynamics in Gene Regulation Optimize Information Flow.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. National Academy of Sciences, 2026. <a href=\"https://doi.org/10.1073/pnas.2524855123\">https://doi.org/10.1073/pnas.2524855123</a>.","ista":"Zoller B, Benichou A, Gregor T, Tkačik G. 2026. Invariant nonequilibrium dynamics in gene regulation optimize information flow. Proceedings of the National Academy of Sciences of the United States of America. 123(28), e2524855123.","ama":"Zoller B, Benichou A, Gregor T, Tkačik G. Invariant nonequilibrium dynamics in gene regulation optimize information flow. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2026;123(28). doi:<a href=\"https://doi.org/10.1073/pnas.2524855123\">10.1073/pnas.2524855123</a>"},"language":[{"iso":"eng"}],"volume":123,"publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"date_updated":"2026-08-04T09:21:10Z","abstract":[{"lang":"eng","text":"Eukaryotic gene regulation relies on stochastic yet controlled promoter switching, in which genes transition between transcriptionally active and inactive states. Despite the molecular complexity of this process, recent studies have revealed a surprising invariance of the “switching correlation time” (TC)—the characteristic decay time of the autocorrelation function of promoter activity fluctuations—across gene expression levels in multiple genes and organisms. A biophysically plausible explanation for this invariance has so far been lacking. Here, we show that this empirical constraint imposes stringent requirements on minimal yet realistic models of transcriptional regulation. Specifically, reproducing TC–invariance requires regulatory architectures with at least four internal states and nonequilibrium dynamics that break detailed balance. Using Bayesian inference on Drosophila gap gene expression data, we demonstrate that such models i) quantitatively reproduce the observed TC–invariance, ii) remain robust to parameter perturbations, and iii) maximize information transmission from transcription factor concentration to gene expression. Remarkably, the TC-invariant modulation strategy we identify as optimal closely parallels contemporary control-theoretic results on the modulation of stochastic switching systems. Taken together, our results suggest that eukaryotic transcriptional regulation operates in a nonequilibrium regime to balance precision, reaction-rate limitations, and energy dissipation, thereby achieving near-optimal information transmission under fundamental physical constraints."}],"OA_place":"publisher","ddc":["570"],"has_accepted_license":"1","title":"Invariant nonequilibrium dynamics in gene regulation optimize information flow","OA_type":"hybrid","related_material":{"link":[{"description":"News on ISTA website","url":"https://ista.ac.at/en/news/the-art-of-proper-flickering/","relation":"press_release"}]},"scopus_import":"1","researchdata_availability":"yes","type":"journal_article","das_tickbox":"1","date_published":"2026-07-14T00:00:00Z","publication":"Proceedings of the National Academy of Sciences of the United States of America","publication_status":"published","supplementarymaterial":"yes","oa_version":"Published Version","file":[{"content_type":"application/pdf","date_updated":"2026-07-20T13:12:47Z","checksum":"f4d82dd706ff1629db68d71190288350","file_name":"2026_PNAS_Zoller.pdf","date_created":"2026-07-20T13:12:47Z","success":1,"relation":"main_file","file_size":24580098,"file_id":"22376","access_level":"open_access","creator":"dernst"}],"author":[{"last_name":"Zoller","full_name":"Zoller, Benjamin","first_name":"Benjamin"},{"full_name":"Benichou, Alexis","first_name":"Alexis","id":"3a67230c-5fc0-11ef-a673-de9a2ffadafe","last_name":"Benichou"},{"last_name":"Gregor","full_name":"Gregor, Thomas","first_name":"Thomas"},{"last_name":"Tkačik","orcid":"0000-0002-6699-1455","full_name":"Tkačik, Gašper","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"pmid":["42406962"]},"project":[{"grant_number":"101118866","_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9","name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos"}],"intvolume":"       123","quality_controlled":"1","year":"2026","month":"07","issue":"28","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","dataavailabilitystatement":"Software code data have been deposited in Institute Pasteur GitHub (https://gitlab.pasteur.fr/tglab/invariantpromoterdynamicspaper) (51).","department":[{"_id":"GaTk"}],"pmid":1,"article_number":"e2524855123","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"}},{"oa_version":"Published Version","file":[{"success":1,"file_size":1888053,"relation":"main_file","file_id":"21314","access_level":"open_access","creator":"dernst","file_name":"2025_PRXLife_Zhang.pdf","checksum":"76ddfee3efdb4c9d085059b5a142ed78","date_created":"2026-02-18T07:57:39Z","content_type":"application/pdf","date_updated":"2026-02-18T07:57:39Z"}],"publication_status":"published","intvolume":"         3","author":[{"last_name":"Zhang","full_name":"Zhang, Chen Y","first_name":"Chen Y","id":"81b43fb8-c9d5-11ef-bf68-ade532a1f204"},{"last_name":"Rosa","full_name":"Rosa, Angelo","first_name":"Angelo"},{"first_name":"Guido","full_name":"Sanguinetti, Guido","last_name":"Sanguinetti"}],"arxiv":1,"external_id":{"arxiv":["2409.14425"]},"month":"10","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","PlanS_conform":"1","issue":"4","quality_controlled":"1","year":"2025","article_type":"original","article_number":"043006","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"department":[{"_id":"GaTk"}],"status":"public","acknowledgement":"G.S. acknowledges co-funding from Next Generation EU, in the context of the National Recovery and Resilience Plan, Investment PE1 - Project FAIR “Future Artificial Intelligence Research”. This resource was co-financed by the Next Generation EU [DM 1555 del 11.10.22]. A.R. acknowledges financial support from PNRR Grant CN 00000013 CN-HPC, M4C2I1.4, spoke 7, funded by Next Generation EU.","article_processing_charge":"Yes","day":"21","publisher":"American Physical Society","_id":"21269","corr_author":"1","oa":1,"date_created":"2026-02-17T07:53:01Z","publication_identifier":{"issn":["2835-8279"]},"abstract":[{"text":"The spatial organization of chromatin within the nucleus plays a crucial role in gene expression and genome function. However, the quantitative relationship between this organization and nuclear biochemical processes remains under debate. In this study, we present a graph-based generative model, bioSBM, designed to capture long-range chromatin interaction patterns from Hi-C data and, importantly, simultaneously link these patterns to biochemical features. Applying bioSBM to Hi-C maps of the GM12878 lymphoblastoid cell line, we identified a latent structure of chromatin interactions, revealing seven distinct communities that strongly align with known biological annotations. Additionally, we infer a linear transformation that maps biochemical observables, such as histone marks, to the parameters of the generative graph model, enabling accurate genome-wide predictions of chromatin contact maps on out-of-sample data, both within the same cell line and on the completely unseen HCT116 cell line under RAD21 depletion. These findings highlight bioSBM's potential as a powerful tool for elucidating the relationship between biochemistry and chromatin architecture and predicting long-range genome organization from independent biochemical data.","lang":"eng"}],"date_updated":"2026-02-18T08:01:00Z","file_date_updated":"2026-02-18T07:57:39Z","citation":{"ieee":"C. Y. Zhang, A. Rosa, and G. Sanguinetti, “bioSBM: A random graph model to integrate epigenomic data in chromatin structure prediction,” <i>PRX Life</i>, vol. 3, no. 4. American Physical Society, 2025.","ista":"Zhang CY, Rosa A, Sanguinetti G. 2025. bioSBM: A random graph model to integrate epigenomic data in chromatin structure prediction. PRX Life. 3(4), 043006.","ama":"Zhang CY, Rosa A, Sanguinetti G. bioSBM: A random graph model to integrate epigenomic data in chromatin structure prediction. <i>PRX Life</i>. 2025;3(4). doi:<a href=\"https://doi.org/10.1103/gy1p-4256\">10.1103/gy1p-4256</a>","apa":"Zhang, C. Y., Rosa, A., &#38; Sanguinetti, G. (2025). bioSBM: A random graph model to integrate epigenomic data in chromatin structure prediction. <i>PRX Life</i>. American Physical Society. <a href=\"https://doi.org/10.1103/gy1p-4256\">https://doi.org/10.1103/gy1p-4256</a>","chicago":"Zhang, Chen Y, Angelo Rosa, and Guido Sanguinetti. “BioSBM: A Random Graph Model to Integrate Epigenomic Data in Chromatin Structure Prediction.” <i>PRX Life</i>. American Physical Society, 2025. <a href=\"https://doi.org/10.1103/gy1p-4256\">https://doi.org/10.1103/gy1p-4256</a>.","short":"C.Y. Zhang, A. Rosa, G. Sanguinetti, PRX Life 3 (2025).","mla":"Zhang, Chen Y., et al. “BioSBM: A Random Graph Model to Integrate Epigenomic Data in Chromatin Structure Prediction.” <i>PRX Life</i>, vol. 3, no. 4, 043006, American Physical Society, 2025, doi:<a href=\"https://doi.org/10.1103/gy1p-4256\">10.1103/gy1p-4256</a>."},"doi":"10.1103/gy1p-4256","volume":3,"language":[{"iso":"eng"}],"OA_type":"gold","ddc":["570"],"OA_place":"publisher","DOAJ_listed":"1","has_accepted_license":"1","title":"bioSBM: A random graph model to integrate epigenomic data in chromatin structure prediction","date_published":"2025-10-21T00:00:00Z","publication":"PRX Life","type":"journal_article"},{"publication_status":"published","file":[{"date_updated":"2025-01-20T10:10:04Z","content_type":"application/pdf","date_created":"2025-01-20T10:10:04Z","file_name":"2025_PNAS_Sokolowski.pdf","checksum":"8dbfc7d495413340225ebfae69b0cf9a","creator":"dernst","file_id":"18862","access_level":"open_access","relation":"main_file","file_size":19073585,"success":1}],"oa_version":"Published Version","external_id":{"isi":["001392772400001"],"pmid":["39752518"]},"author":[{"orcid":"0000-0002-1287-3779","last_name":"Sokolowski","full_name":"Sokolowski, Thomas R","id":"3E999752-F248-11E8-B48F-1D18A9856A87","first_name":"Thomas R"},{"last_name":"Gregor","full_name":"Gregor, Thomas","first_name":"Thomas"},{"first_name":"William","full_name":"Bialek, William","last_name":"Bialek"},{"full_name":"Tkačik, Gašper","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6699-1455","last_name":"Tkačik"}],"intvolume":"       122","project":[{"name":"Biophysics of information processing in gene regulation","_id":"254E9036-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P28844-B27"},{"grant_number":"101118866","name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos","_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9"},{"grant_number":"RGP0034/2018","_id":"2665AAFE-B435-11E9-9278-68D0E5697425","name":"Can evolution minimize spurious signaling crosstalk to reach optimal performance?"}],"year":"2025","quality_controlled":"1","issue":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"01","department":[{"_id":"GaTk"}],"isi":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"pmid":1,"article_number":"e2402925121","article_type":"original","date_created":"2025-01-19T23:01:50Z","oa":1,"corr_author":"1","_id":"18849","publisher":"National Academy of Sciences","day":"07","article_processing_charge":"Yes (in subscription journal)","acknowledgement":"We thank Nicholas H. Barton for his comments on the manuscript, Benjamin Zoller for helpful discussions, and Aleksandra Walczak and Curtis Callan for early collaborations that shaped this work. Special thanks to Eric F. Wieschaus for many persistently inspiring conversations. This work was supported in part by the Human Frontiers Science Program; the Austrian Science Fund (FWF P28844); by the European Research Council grant DynaTrans (101118866); by U.S. NSF, through the Center for the Physics of Biological Function (PHY–1734030); by NIH Grants R01GM097275, U01DA047730, and U01DK127429; by the John Simon Guggenheim Memorial Foundation; and by the LOEWE priority program “Center for Multiscale Modeling in Life Sciences” (CMMS), sponsored by the Hessian Ministry for Science and Research, Arts and Culture (HMWK).","status":"public","volume":122,"language":[{"iso":"eng"}],"citation":{"ieee":"T. R. Sokolowski, T. Gregor, W. Bialek, and G. Tkačik, “Deriving a genetic regulatory network from an optimization principle,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 1. National Academy of Sciences, 2025.","ama":"Sokolowski TR, Gregor T, Bialek W, Tkačik G. Deriving a genetic regulatory network from an optimization principle. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(1). doi:<a href=\"https://doi.org/10.1073/pnas.2402925121\">10.1073/pnas.2402925121</a>","ista":"Sokolowski TR, Gregor T, Bialek W, Tkačik G. 2025. Deriving a genetic regulatory network from an optimization principle. Proceedings of the National Academy of Sciences. 122(1), e2402925121.","apa":"Sokolowski, T. R., Gregor, T., Bialek, W., &#38; Tkačik, G. (2025). Deriving a genetic regulatory network from an optimization principle. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2402925121\">https://doi.org/10.1073/pnas.2402925121</a>","chicago":"Sokolowski, Thomas R, Thomas Gregor, William Bialek, and Gašper Tkačik. “Deriving a Genetic Regulatory Network from an Optimization Principle.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2402925121\">https://doi.org/10.1073/pnas.2402925121</a>.","short":"T.R. Sokolowski, T. Gregor, W. Bialek, G. Tkačik, Proceedings of the National Academy of Sciences 122 (2025).","mla":"Sokolowski, Thomas R., et al. “Deriving a Genetic Regulatory Network from an Optimization Principle.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 1, e2402925121, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2402925121\">10.1073/pnas.2402925121</a>."},"file_date_updated":"2025-01-20T10:10:04Z","doi":"10.1073/pnas.2402925121","date_updated":"2026-02-16T12:26:51Z","abstract":[{"lang":"eng","text":"Many biological systems operate near the physical limits to their performance, suggesting that aspects of their behavior and underlying mechanisms could be derived from optimization principles. However, such principles have often been applied only in simplified models. Here, we explore a detailed mechanistic model of the gap gene network in the Drosophila embryo, optimizing its 50+ parameters to maximize the information that gene expression levels provide about nuclear positions. This optimization is conducted under realistic constraints, such as limits on the number of available molecules. Remarkably, the optimal networks we derive closely match the architecture and spatial gene expression profiles observed in the real organism. Our framework quantifies the tradeoffs involved in maximizing functional performance and allows for the exploration of alternative network configurations, addressing the question of which features are necessary and which are contingent. Our results suggest that multiple solutions to the optimization problem might exist across closely related organisms, offering insights into the evolution of gene regulatory networks."}],"publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"has_accepted_license":"1","title":"Deriving a genetic regulatory network from an optimization principle","OA_place":"publisher","ddc":["570"],"OA_type":"hybrid","type":"journal_article","scopus_import":"1","publication":"Proceedings of the National Academy of Sciences","date_published":"2025-01-07T00:00:00Z"},{"month":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","issue":"1","quality_controlled":"1","year":"2025","article_type":"original","article_number":"e2411887121","pmid":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"isi":1,"department":[{"_id":"GaTk"}],"oa_version":"Published Version","file":[{"date_created":"2025-01-20T09:38:32Z","checksum":"86a8d25a6e282aeb4128f1d0b86ff911","file_name":"2025_PNAS_Perkins.pdf","creator":"dernst","access_level":"open_access","file_id":"18859","file_size":30943709,"relation":"main_file","success":1,"date_updated":"2025-01-20T09:38:32Z","content_type":"application/pdf"}],"publication_status":"published","project":[{"name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos","_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9","grant_number":"101118866"}],"intvolume":"       122","author":[{"first_name":"Mindy Liu","full_name":"Perkins, Mindy Liu","last_name":"Perkins"},{"full_name":"Crocker, Justin","first_name":"Justin","last_name":"Crocker"},{"first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455"}],"external_id":{"pmid":["39793086"],"isi":["001392765300001"]},"APC_amount":"3261,23 EUR","OA_type":"hybrid","ddc":["570"],"OA_place":"publisher","title":"Chromatin enables precise and scalable gene regulation with factors of limited specificity","has_accepted_license":"1","date_published":"2025-01-07T00:00:00Z","publication":"Proceedings of the National Academy of Sciences","scopus_import":"1","related_material":{"link":[{"relation":"software","url":"https://github.com/officerredshirt/network_crosstalk"}]},"type":"journal_article","acknowledgement":"M.L.P. was supported by the European Molecular Biology Laboratory (EMBL) Interdisciplinary Postdoc Programme (EIPOD4 fellowships), cofunded by Marie SkÅ‚odowska-Curie Actions (Grant Agreement No. 847543). J.C. and M.L.P. were supported by EMBL Core Funding and Theory@EMBL. This work is supported by European Research Council Grant DynaTrans (101118866) to G.T. We would like to thank the members of the J.C. and G.T. groups, especially Natalia Misunou, Michal Hledík, and Réka Borbély, for helpful feedback and discussion. We also thank EMBL IT Services for the use of high performance computing resources.","status":"public","article_processing_charge":"No","publisher":"National Academy of Sciences","day":"07","_id":"18850","corr_author":"1","oa":1,"date_created":"2025-01-19T23:01:51Z","publication_identifier":{"eissn":["1091-6490"],"issn":["0027-8424"]},"abstract":[{"text":"Biophysical constraints limit the specificity with which transcription factors (TFs) can target regulatory DNA. While individual nontarget binding events may be low affinity, the sheer number of such interactions could present a challenge for gene regulation by degrading its precision or possibly leading to an erroneous induction state. Chromatin can prevent nontarget binding by rendering DNA physically inaccessible to TFs, at the cost of energy-consuming remodeling orchestrated by pioneer factors (PFs). Under what conditions and by how much can chromatin reduce regulatory errors on a global scale? We use a theoretical approach to compare two scenarios for gene regulation: one that relies on TF binding to free DNA alone and one that uses a combination of TFs and chromatin-regulating PFs to achieve desired gene expression patterns. We find, first, that chromatin effectively silences groups of genes that should be simultaneously OFF, thereby allowing more accurate graded control of expression for the remaining ON genes. Second, chromatin buffers the deleterious consequences of nontarget binding as the number of OFF genes grows, permitting a substantial expansion in regulatory complexity. Third, chromatin-based regulation productively co-opts nontarget TF binding for ON genes in order to establish a “leaky” baseline expression level, which targeted activator or repressor binding subsequently up- or down-modulates. Thus, on a global scale, using chromatin simultaneously alleviates pressure for high specificity of regulatory interactions and enables an increase in genome size with minimal impact on global expression error.","lang":"eng"}],"date_updated":"2026-05-06T12:43:59Z","doi":"10.1073/pnas.2411887121","citation":{"short":"M.L. Perkins, J. Crocker, G. Tkačik, Proceedings of the National Academy of Sciences 122 (2025).","mla":"Perkins, Mindy Liu, et al. “Chromatin Enables Precise and Scalable Gene Regulation with Factors of Limited Specificity.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 1, e2411887121, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2411887121\">10.1073/pnas.2411887121</a>.","ieee":"M. L. Perkins, J. Crocker, and G. Tkačik, “Chromatin enables precise and scalable gene regulation with factors of limited specificity,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 1. National Academy of Sciences, 2025.","chicago":"Perkins, Mindy Liu, Justin Crocker, and Gašper Tkačik. “Chromatin Enables Precise and Scalable Gene Regulation with Factors of Limited Specificity.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2411887121\">https://doi.org/10.1073/pnas.2411887121</a>.","apa":"Perkins, M. L., Crocker, J., &#38; Tkačik, G. (2025). Chromatin enables precise and scalable gene regulation with factors of limited specificity. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2411887121\">https://doi.org/10.1073/pnas.2411887121</a>","ista":"Perkins ML, Crocker J, Tkačik G. 2025. Chromatin enables precise and scalable gene regulation with factors of limited specificity. Proceedings of the National Academy of Sciences. 122(1), e2411887121.","ama":"Perkins ML, Crocker J, Tkačik G. Chromatin enables precise and scalable gene regulation with factors of limited specificity. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(1). doi:<a href=\"https://doi.org/10.1073/pnas.2411887121\">10.1073/pnas.2411887121</a>"},"file_date_updated":"2025-01-20T09:38:32Z","language":[{"iso":"eng"}],"volume":122},{"scopus_import":"1","type":"journal_article","date_published":"2025-02-01T00:00:00Z","publication":"Genetics","ddc":["570"],"OA_place":"publisher","title":"Linking molecular mechanisms to their evolutionary consequences: a primer","has_accepted_license":"1","OA_type":"hybrid","citation":{"mla":"Grah, Rok, et al. “Linking Molecular Mechanisms to Their Evolutionary Consequences: A Primer.” <i>Genetics</i>, vol. 229, no. 2, iyae191, Oxford University Press, 2025, doi:<a href=\"https://doi.org/10.1093/genetics/iyae191\">10.1093/genetics/iyae191</a>.","short":"R. Grah, C.C. Guet, G. Tkačik, M. Lagator, Genetics 229 (2025).","apa":"Grah, R., Guet, C. C., Tkačik, G., &#38; Lagator, M. (2025). Linking molecular mechanisms to their evolutionary consequences: a primer. <i>Genetics</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/genetics/iyae191\">https://doi.org/10.1093/genetics/iyae191</a>","chicago":"Grah, Rok, Calin C Guet, Gašper Tkačik, and Mato Lagator. “Linking Molecular Mechanisms to Their Evolutionary Consequences: A Primer.” <i>Genetics</i>. Oxford University Press, 2025. <a href=\"https://doi.org/10.1093/genetics/iyae191\">https://doi.org/10.1093/genetics/iyae191</a>.","ista":"Grah R, Guet CC, Tkačik G, Lagator M. 2025. Linking molecular mechanisms to their evolutionary consequences: a primer. Genetics. 229(2), iyae191.","ama":"Grah R, Guet CC, Tkačik G, Lagator M. Linking molecular mechanisms to their evolutionary consequences: a primer. <i>Genetics</i>. 2025;229(2). doi:<a href=\"https://doi.org/10.1093/genetics/iyae191\">10.1093/genetics/iyae191</a>","ieee":"R. Grah, C. C. Guet, G. Tkačik, and M. Lagator, “Linking molecular mechanisms to their evolutionary consequences: a primer,” <i>Genetics</i>, vol. 229, no. 2. Oxford University Press, 2025."},"file_date_updated":"2025-04-16T09:41:04Z","doi":"10.1093/genetics/iyae191","language":[{"iso":"eng"}],"volume":229,"publication_identifier":{"eissn":["1943-2631"]},"abstract":[{"text":"A major obstacle to predictive understanding of evolution stems from the complexity of biological systems, which prevents detailed characterization of key evolutionary properties. Here, we highlight some of the major sources of complexity that arise when relating molecular mechanisms to their evolutionary consequences and ask whether accounting for every mechanistic detail is important to accurately predict evolutionary outcomes. To do this, we developed a mechanistic model of a bacterial promoter regulated by 2 proteins, allowing us to connect any promoter genotype to 6 phenotypes that capture the dynamics of gene expression following an environmental switch. Accounting for the mechanisms that govern how this system works enabled us to provide an in-depth picture of how regulated bacterial promoters might evolve. More importantly, we used the model to explore which factors that contribute to the complexity of this system are essential for understanding its evolution, and which can be simplified without information loss. We found that several key evolutionary properties—the distribution of phenotypic and fitness effects of mutations, the evolutionary trajectories during selection for regulation—can be accurately captured without accounting for all, or even most, parameters of the system. Our findings point to the need for a mechanistic approach to studying evolution, as it enables tackling biological complexity and in doing so improves the ability to predict evolutionary outcomes.","lang":"eng"}],"date_updated":"2025-05-19T14:08:02Z","day":"01","publisher":"Oxford University Press","_id":"18936","corr_author":"1","oa":1,"date_created":"2025-01-29T08:21:35Z","acknowledgement":"The authors thank Nick Barton, Stepan Denisov, Claudia Igler, Srdjan Sarikas, Anna Staron, and the anonymous reviewers for useful comments and discussions that helped improve our work.\r\nFunding for this work was provided by the Wellcome Trust–Royal Society Sir Henry Dale Fellowship (216779/Z/19/Z) and the Royal Society Research Grant (RG\\R2\\232522) to M.L.","status":"public","article_processing_charge":"Yes (in subscription journal)","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"article_number":"iyae191","article_type":"original","pmid":1,"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"isi":1,"quality_controlled":"1","year":"2025","month":"02","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","issue":"2","author":[{"full_name":"Grah, Rok","id":"483E70DE-F248-11E8-B48F-1D18A9856A87","first_name":"Rok","orcid":"0000-0003-2539-3560","last_name":"Grah"},{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C","last_name":"Guet","orcid":"0000-0001-6220-2052"},{"last_name":"Tkačik","orcid":"0000-0002-6699-1455","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper"},{"full_name":"Lagator, Mato","id":"345D25EC-F248-11E8-B48F-1D18A9856A87","first_name":"Mato","last_name":"Lagator"}],"external_id":{"pmid":["39601269"],"isi":["001379194200001"]},"intvolume":"       229","publication_status":"published","oa_version":"Published Version","file":[{"date_created":"2025-04-16T09:41:04Z","checksum":"f730e416795969449ef49d97b82ac494","file_name":"2025_Genetics_Grah.pdf","file_size":1511688,"relation":"main_file","success":1,"creator":"dernst","access_level":"open_access","file_id":"19580","content_type":"application/pdf","date_updated":"2025-04-16T09:41:04Z"}]},{"day":"04","publisher":"Institute of Science and Technology Austria","_id":"18991","corr_author":"1","oa":1,"date_created":"2025-02-04T10:36:18Z","acknowledgement":"Thanks to Rebecca Morse for performing one of the experiments under H.S.C.C. supervision and Jago Wallenschus for technical support, especially with maze design.","status":"public","article_processing_charge":"No","doi":"10.15479/AT:ISTA:18991","citation":{"mla":"Chiossi, Heloisa S. C. <i>Research Data for the Publication “Learning Reshapes the Hippocampal Representation Hierarchy.”</i> Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18991\">10.15479/AT:ISTA:18991</a>.","short":"H.S.C. Chiossi, (2025).","apa":"Chiossi, H. S. C. (2025). Research data for the publication “Learning reshapes the hippocampal representation hierarchy.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:18991\">https://doi.org/10.15479/AT:ISTA:18991</a>","chicago":"Chiossi, Heloisa S. C. “Research Data for the Publication ‘Learning Reshapes the Hippocampal Representation Hierarchy.’” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT:ISTA:18991\">https://doi.org/10.15479/AT:ISTA:18991</a>.","ista":"Chiossi HSC. 2025. Research data for the publication ‘Learning reshapes the hippocampal representation hierarchy’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:18991\">10.15479/AT:ISTA:18991</a>.","ama":"Chiossi HSC. Research data for the publication “Learning reshapes the hippocampal representation hierarchy.” 2025. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:18991\">10.15479/AT:ISTA:18991</a>","ieee":"H. S. C. Chiossi, “Research data for the publication ‘Learning reshapes the hippocampal representation hierarchy.’” Institute of Science and Technology Austria, 2025."},"file_date_updated":"2025-02-04T10:18:33Z","abstract":[{"lang":"eng","text":"Research data for the article \"Learning reshapes the hippocampal representation hierarchy\" from Chiossi et al. (PNAS, 2025). The data includes hippocampal CA1 unit activity and behaviour tracking of 5 Long Evans rats during the learning of an associative memory task. Detailed information can be found in the 'readme.txt' file."}],"date_updated":"2026-05-06T13:12:00Z","ddc":["570"],"OA_place":"repository","contributor":[{"first_name":"Michele","contributor_type":"researcher","id":"30BD0376-F248-11E8-B48F-1D18A9856A87","last_name":"Nardin","orcid":"0000-0001-8849-6570"},{"first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","contributor_type":"supervisor","orcid":"0000-0002-6699-1455","last_name":"Tkačik"},{"last_name":"Csicsvari","orcid":"0000-0002-5193-4036","contributor_type":"supervisor","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","first_name":"Jozsef L"}],"title":"Research data for the publication \"Learning reshapes the hippocampal representation hierarchy\"","has_accepted_license":"1","OA_type":"gold","related_material":{"record":[{"id":"19453","relation":"used_in_publication","status":"public"}]},"type":"research_data","date_published":"2025-02-04T00:00:00Z","oa_version":"Published 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Heloisa"}],"year":"2025","keyword":["hippocampus","electrophysiology","behavior"],"month":"02","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"GradSch"},{"_id":"JoCs"},{"_id":"GaTk"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"M-Shop"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"}},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","OA_type":"gold","month":"03","has_accepted_license":"1","title":"Data for \"Pulsatile basal gene expression as a fitness determinant in bacteria\"","year":"2025","ddc":["570"],"OA_place":"repository","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"date_published":"2025-03-04T00:00:00Z","type":"research_data","department":[{"_id":"CaGu"},{"_id":"Bio"},{"_id":"FyKo"},{"_id":"GaTk"}],"related_material":{"record":[{"status":"public","id":"19626","relation":"used_in_publication"}]},"status":"public","file":[{"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","date_updated":"2025-03-04T13:08:52Z","date_created":"2025-03-04T13:08:52Z","file_name":"Data1.xlsx","checksum":"11a5bab307a4e1e1598a1577d8a2fbb5","relation":"main_file","file_size":269054,"success":1,"creator":"dernst","access_level":"open_access","file_id":"19295"},{"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","date_updated":"2025-03-04T13:08:52Z","checksum":"3b057894322639f0c1e11fb2e84173e6","file_name":"Data2.xlsx","date_created":"2025-03-04T13:08:52Z","success":1,"relation":"main_file","file_size":87143,"access_level":"open_access","file_id":"19296","creator":"dernst"},{"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","date_updated":"2025-03-04T13:08:52Z","date_created":"2025-03-04T13:08:52Z","file_name":"Data3.xlsx","checksum":"a551e1b79a138bb97ab96979aa475b3c","file_size":129101,"relation":"main_file","success":1,"creator":"dernst","file_id":"19297","access_level":"open_access"},{"content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","date_updated":"2025-03-04T13:08:52Z","relation":"main_file","file_size":86243,"success":1,"creator":"dernst","file_id":"19298","access_level":"open_access","date_created":"2025-03-04T13:08:52Z","checksum":"d6909c9bf111f859058082b1a2f970c4","file_name":"Data4.xlsx"},{"date_updated":"2025-03-04T13:08:52Z","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet","creator":"dernst","file_id":"19299","access_level":"open_access","relation":"main_file","file_size":26049,"success":1,"date_created":"2025-03-04T13:08:52Z","checksum":"e5725a3a118a3f06846104906c8792c7","file_name":"Data5.xlsx"},{"date_created":"2025-03-04T13:08:52Z","file_name":"RawData_2_3.xlsx","checksum":"16763c127049f14bd587dc885677dce1","creator":"dernst","file_id":"19300","access_level":"open_access","relation":"main_file","file_size":7327253,"success":1,"date_updated":"2025-03-04T13:08:52Z","content_type":"application/vnd.openxmlformats-officedocument.spreadsheetml.sheet"},{"content_type":"text/plain","date_updated":"2025-03-05T07:39:38Z","date_created":"2025-03-05T07:39:38Z","file_name":"Readme.txt","checksum":"2f3e1a368b4e3abc46bf37e02724f0f4","file_size":606,"relation":"main_file","success":1,"creator":"dernst","file_id":"19301","access_level":"open_access"}],"article_processing_charge":"No","oa_version":"Published Version","corr_author":"1","oa":1,"date_created":"2025-03-04T13:27:21Z","day":"04","publisher":"Institute of Science and Technology Austria","_id":"19294","abstract":[{"text":"Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of non-functional “promoter leakiness”, merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the non-canonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g. control of costly-to-induce multi-drug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multi-drug resistance is crucial for effective public health measures.","lang":"eng"}],"date_updated":"2026-05-20T08:33:07Z","author":[{"orcid":"0000-0002-3809-0449","last_name":"Jain","first_name":"Kirti","id":"330F0278-F248-11E8-B48F-1D18A9856A87","full_name":"Jain, Kirti"},{"orcid":"0000-0001-9843-3522","last_name":"Hauschild","full_name":"Hauschild, Robert","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"id":"C4558D3C-6102-11E9-A62E-F418E6697425","first_name":"Olga","full_name":"Bochkareva, Olga","last_name":"Bochkareva","orcid":"0000-0003-1006-6639"},{"orcid":"0000-0001-9480-5261","last_name":"Römhild","full_name":"Römhild, Roderich","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","first_name":"Roderich"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","full_name":"Tkačik, Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455"},{"full_name":"Guet, Calin C","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","last_name":"Guet"}],"doi":"10.15479/AT:ISTA:19294","citation":{"short":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, (2025).","mla":"Jain, Kirti, et al. <i>Data for “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.”</i> Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:19294\">10.15479/AT:ISTA:19294</a>.","ieee":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet, “Data for ‘Pulsatile basal gene expression as a fitness determinant in bacteria.’” Institute of Science and Technology Austria, 2025.","apa":"Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., &#38; Guet, C. C. (2025). Data for “Pulsatile basal gene expression as a fitness determinant in bacteria.” Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:19294\">https://doi.org/10.15479/AT:ISTA:19294</a>","chicago":"Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper Tkačik, and Calin C Guet. “Data for ‘Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.’” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT:ISTA:19294\">https://doi.org/10.15479/AT:ISTA:19294</a>.","ista":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Data for ‘Pulsatile basal gene expression as a fitness determinant in bacteria’, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:19294\">10.15479/AT:ISTA:19294</a>.","ama":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Data for “Pulsatile basal gene expression as a fitness determinant in bacteria.” 2025. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:19294\">10.15479/AT:ISTA:19294</a>"},"file_date_updated":"2025-03-05T07:39:38Z"},{"pmid":1,"article_type":"original","article_number":"e2417025122","isi":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"department":[{"_id":"GaTk"},{"_id":"JoCs"}],"month":"03","issue":"11","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","year":"2025","project":[{"grant_number":"665385","call_identifier":"H2020","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"}],"intvolume":"       122","author":[{"last_name":"Chiossi","orcid":"0009-0004-2973-278X","full_name":"Chiossi, Heloisa","id":"2BBA502C-F248-11E8-B48F-1D18A9856A87","first_name":"Heloisa"},{"id":"30BD0376-F248-11E8-B48F-1D18A9856A87","first_name":"Michele","full_name":"Nardin, Michele","last_name":"Nardin","orcid":"0000-0001-8849-6570"},{"full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","orcid":"0000-0002-6699-1455","last_name":"Tkačik"},{"last_name":"Csicsvari","orcid":"0000-0002-5193-4036","first_name":"Jozsef L","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","full_name":"Csicsvari, Jozsef L"}],"external_id":{"isi":["001459499500001"],"pmid":["40063792"]},"oa_version":"Published Version","file":[{"date_updated":"2025-03-25T07:49:04Z","content_type":"application/pdf","creator":"dernst","file_id":"19454","access_level":"open_access","file_size":1553502,"relation":"main_file","success":1,"date_created":"2025-03-25T07:49:04Z","checksum":"1217207c254553154faa065964990988","file_name":"2025_PNAS_Chiossi.pdf"}],"publication_status":"published","date_published":"2025-03-10T00:00:00Z","ec_funded":1,"publication":"Proceedings of the National Academy of Sciences","related_material":{"record":[{"relation":"research_data","id":"18991","status":"public"}],"link":[{"relation":"software","url":"https://github.com/hchiossi/hpc-hierarchy"}]},"scopus_import":"1","type":"journal_article","APC_amount":"3317,75 EUR","OA_type":"hybrid","OA_place":"publisher","ddc":["570"],"title":"Learning reshapes the hippocampal representation hierarchy","has_accepted_license":"1","publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"date_updated":"2026-05-06T13:12:01Z","abstract":[{"lang":"eng","text":"A key feature of biological and artificial neural networks is the progressive refinement of their neural representations with experience. In neuroscience, this fact has inspired several recent studies in sensory and motor systems. However, less is known about how higher associational cortical areas, such as the hippocampus, modify representations throughout the learning of complex tasks. Here, we focus on associative learning, a process that requires forming a connection between the representations of different variables for appropriate behavioral response. We trained rats in a space-context associative task and monitored hippocampal neural activity throughout the entire learning period, over several days. This allowed us to assess changes in the representations of context, movement direction, and position, as well as their relationship to behavior. We identified a hierarchical representational structure in the encoding of these three task variables that was preserved throughout learning. Nevertheless, we also observed changes at the lower levels of the hierarchy where context was encoded. These changes were local in neural activity space and restricted to physical positions where context identification was necessary for correct decision-making, supporting better context decoding and contextual code compression. Our results demonstrate that the hippocampal code not only accommodates hierarchical relationships between different variables but also enables efficient learning through minimal changes in neural activity space. Beyond the hippocampus, our work reveals a representation learning mechanism that might be implemented in other biological and artificial networks performing similar tasks."}],"citation":{"mla":"Chiossi, Heloisa S. C., et al. “Learning Reshapes the Hippocampal Representation Hierarchy.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 11, e2417025122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2417025122\">10.1073/pnas.2417025122</a>.","short":"H.S.C. Chiossi, M. Nardin, G. Tkačik, J.L. Csicsvari, Proceedings of the National Academy of Sciences 122 (2025).","ama":"Chiossi HSC, Nardin M, Tkačik G, Csicsvari JL. Learning reshapes the hippocampal representation hierarchy. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(11). doi:<a href=\"https://doi.org/10.1073/pnas.2417025122\">10.1073/pnas.2417025122</a>","ista":"Chiossi HSC, Nardin M, Tkačik G, Csicsvari JL. 2025. Learning reshapes the hippocampal representation hierarchy. Proceedings of the National Academy of Sciences. 122(11), e2417025122.","apa":"Chiossi, H. S. C., Nardin, M., Tkačik, G., &#38; Csicsvari, J. L. (2025). Learning reshapes the hippocampal representation hierarchy. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2417025122\">https://doi.org/10.1073/pnas.2417025122</a>","chicago":"Chiossi, Heloisa S. C., Michele Nardin, Gašper Tkačik, and Jozsef L Csicsvari. “Learning Reshapes the Hippocampal Representation Hierarchy.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2417025122\">https://doi.org/10.1073/pnas.2417025122</a>.","ieee":"H. S. C. Chiossi, M. Nardin, G. Tkačik, and J. L. Csicsvari, “Learning reshapes the hippocampal representation hierarchy,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 11. National Academy of Sciences, 2025."},"file_date_updated":"2025-03-25T07:49:04Z","doi":"10.1073/pnas.2417025122","volume":122,"language":[{"iso":"eng"}],"article_processing_charge":"Yes (in subscription journal)","acknowledgement":"We would like to thank Rebecca Morse for performing the recordings in one of the animals under the supervision of H.S.C.C., Jago Wallenschus for the technical support, especially with maze design, Wiktor Mlynarski for the advice and discussions and Andrea Cumpelik for suggestions during the writing. M.N. was supported by the Howard Hughes Medical Institute. H.S.C.C. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 665385.","status":"public","_id":"19453","day":"10","publisher":"National Academy of Sciences","date_created":"2025-03-25T07:38:35Z","oa":1,"corr_author":"1"},{"publication_identifier":{"issn":["0027-8424"],"eissn":["1091-6490"]},"abstract":[{"lang":"eng","text":"Active regulation of gene expression, orchestrated by complex interactions of activators and repressors at promoters, controls the fate of organisms. In contrast, basal expression at uninduced promoters is considered to be a dynamically inert mode of nonfunctional “promoter leakiness,” merely a byproduct of transcriptional regulation. Here, we investigate the basal expression mode of the mar operon, the main regulator of intrinsic multiple antibiotic resistance in Escherichia coli, and link its dynamic properties to the noncanonical, yet highly conserved start codon of marR across Enterobacteriaceae. Real-time, single-cell measurements across tens of generations reveal that basal expression consists of rare stochastic gene expression pulses, which maximize variability in wildtype and, surprisingly, transiently accelerate cellular elongation rates. Competition experiments show that basal expression confers fitness advantages to wildtype across several transitions between exponential and stationary growth by shortening lag times. The dynamically rich basal expression of the mar operon has likely been evolutionarily maintained for its role in growth homeostasis of Enterobacteria within the gut environment, thereby allowing other ancillary gene regulatory roles to evolve, e.g., control of costly-to-induce multidrug efflux pumps. Understanding the complex selection forces governing genetic systems involved in intrinsic multidrug resistance is crucial for effective public health measures."}],"date_updated":"2026-05-20T08:33:08Z","citation":{"short":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, C.C. Guet, Proceedings of the National Academy of Sciences 122 (2025).","mla":"Jain, Kirti, et al. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15, e2413709122, National Academy of Sciences, 2025, doi:<a href=\"https://doi.org/10.1073/pnas.2413709122\">10.1073/pnas.2413709122</a>.","ieee":"K. Jain, R. Hauschild, O. Bochkareva, R. Römhild, G. Tkačik, and C. C. Guet, “Pulsatile basal gene expression as a fitness determinant in bacteria,” <i>Proceedings of the National Academy of Sciences</i>, vol. 122, no. 15. National Academy of Sciences, 2025.","ama":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. Pulsatile basal gene expression as a fitness determinant in bacteria. <i>Proceedings of the National Academy of Sciences</i>. 2025;122(15). doi:<a href=\"https://doi.org/10.1073/pnas.2413709122\">10.1073/pnas.2413709122</a>","ista":"Jain K, Hauschild R, Bochkareva O, Römhild R, Tkačik G, Guet CC. 2025. Pulsatile basal gene expression as a fitness determinant in bacteria. Proceedings of the National Academy of Sciences. 122(15), e2413709122.","chicago":"Jain, Kirti, Robert Hauschild, Olga Bochkareva, Roderich Römhild, Gašper Tkačik, and Calin C Guet. “Pulsatile Basal Gene Expression as a Fitness Determinant in Bacteria.” <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences, 2025. <a href=\"https://doi.org/10.1073/pnas.2413709122\">https://doi.org/10.1073/pnas.2413709122</a>.","apa":"Jain, K., Hauschild, R., Bochkareva, O., Römhild, R., Tkačik, G., &#38; Guet, C. C. (2025). Pulsatile basal gene expression as a fitness determinant in bacteria. <i>Proceedings of the National Academy of Sciences</i>. National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2413709122\">https://doi.org/10.1073/pnas.2413709122</a>"},"file_date_updated":"2025-06-24T07:27:43Z","doi":"10.1073/pnas.2413709122","volume":122,"language":[{"iso":"eng"}],"acknowledgement":"K.J. thanks B. Wu, I. Tomanek, K. Tomasek for detailed discussions on the manuscript, all other members from the Guet laboratory for valuable feedback, R. Chait, & Imaging and Optics Facility, Institute of Science and Technology Austria for helping with microscopy, Dr. Sudha Rao and Dr. Raja Mugasimangalam, Genotypic Technology India for allowing time off to address the revisions. K.J. acknowledges Institute of Science and Technology fellowship IC1006FELL02, R.H. was supported in part by Chan Zuckerberg Initiative and Donor Advised-Fund grant 2020-225401 (https://doi.org/10.37921/120055ratwvi), O.O.B. acknowledges Fonds Zur Förderung der Wissenschaftlichen Forschung (FWF) Grant ESP253-B, R.R. acknowledges FWF Grant 10.55776/ESP219, C.C.G. acknowledges FWF I5127-B.","status":"public","article_processing_charge":"Yes (in subscription journal)","day":"15","publisher":"National Academy of Sciences","_id":"19626","corr_author":"1","oa":1,"date_created":"2025-04-27T22:02:13Z","date_published":"2025-04-15T00:00:00Z","publication":"Proceedings of the National Academy of Sciences","scopus_import":"1","related_material":{"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/clockwork-just-for-antibiotic-resistance/","description":"News on ISTA website"}],"record":[{"id":"19294","relation":"research_data","status":"public"}]},"type":"journal_article","APC_amount":"5949 EUR","OA_type":"hybrid","ddc":["570"],"OA_place":"publisher","title":"Pulsatile basal gene expression as a fitness determinant in bacteria","has_accepted_license":"1","project":[{"grant_number":"CZI01","_id":"c08e9ad1-5a5b-11eb-8a69-9d1cf3b07473","name":"Tools for automation and feedback microscopy"},{"grant_number":"E219","_id":"bd6f94d1-d553-11ed-ba76-ae9f07250f74","name":"Non-canonical antibiotic interactions"},{"_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181","name":"Evolutionary analysis of gene regulation","grant_number":"I05127"}],"intvolume":"       122","author":[{"id":"330F0278-F248-11E8-B48F-1D18A9856A87","first_name":"Kirti","full_name":"Jain, Kirti","orcid":"0000-0002-3809-0449","last_name":"Jain"},{"last_name":"Hauschild","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert","first_name":"Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Bochkareva","orcid":"0000-0003-1006-6639","first_name":"Olga","id":"C4558D3C-6102-11E9-A62E-F418E6697425","full_name":"Bochkareva, Olga"},{"orcid":"0000-0001-9480-5261","last_name":"Römhild","full_name":"Römhild, Roderich","first_name":"Roderich","id":"68E56E44-62B0-11EA-B963-444F3DDC885E"},{"full_name":"Tkačik, Gašper","first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","last_name":"Tkačik","orcid":"0000-0002-6699-1455"},{"orcid":"0000-0001-6220-2052","last_name":"Guet","first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"}],"external_id":{"pmid":["40193613"],"isi":["001471235200001"]},"oa_version":"Published Version","file":[{"file_id":"19888","access_level":"open_access","creator":"dernst","success":1,"relation":"main_file","file_size":2949523,"file_name":"2025_PNAS_Jain.pdf","checksum":"115a687f40009660eb4b38b4f6559d41","date_created":"2025-06-24T07:27:43Z","date_updated":"2025-06-24T07:27:43Z","content_type":"application/pdf"}],"publication_status":"published","article_type":"original","article_number":"e2413709122","acknowledged_ssus":[{"_id":"Bio"}],"pmid":1,"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"isi":1,"department":[{"_id":"CaGu"},{"_id":"Bio"},{"_id":"FyKo"},{"_id":"GaTk"}],"month":"04","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","issue":"15","quality_controlled":"1","year":"2025"},{"related_material":{"record":[{"relation":"used_in_publication","id":"19785","status":"public"}]},"type":"research_data","date_published":"2025-05-08T00:00:00Z","ddc":["570"],"OA_place":"publisher","contributor":[{"first_name":"Bor","contributor_type":"researcher","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6041-254X","last_name":"Kavcic"}],"title":"Token-driven totally asymmetric simple exclusion processes","has_accepted_license":"1","OA_type":"gold","file_date_updated":"2025-05-12T07:36:23Z","doi":"10.15479/AT:ISTA:19658","citation":{"mla":"Tkačik, Gašper. <i>Token-Driven Totally Asymmetric Simple Exclusion Processes</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:19658\">10.15479/AT:ISTA:19658</a>.","short":"G. Tkačik, (2025).","ista":"Tkačik G. 2025. Token-driven totally asymmetric simple exclusion processes, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:19658\">10.15479/AT:ISTA:19658</a>.","ama":"Tkačik G. Token-driven totally asymmetric simple exclusion processes. 2025. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:19658\">10.15479/AT:ISTA:19658</a>","apa":"Tkačik, G. (2025). Token-driven totally asymmetric simple exclusion processes. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:19658\">https://doi.org/10.15479/AT:ISTA:19658</a>","chicago":"Tkačik, Gašper. “Token-Driven Totally Asymmetric Simple Exclusion Processes.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT:ISTA:19658\">https://doi.org/10.15479/AT:ISTA:19658</a>.","ieee":"G. Tkačik, “Token-driven totally asymmetric simple exclusion processes.” Institute of Science and Technology Austria, 2025."},"abstract":[{"text":"We consider a family of totally asymmetric simple exclusion processes (TASEPs), consisting of particles on a lattice that require binding by a \"token\" in various physical configurations to advance over the lattice. Using a combination of theory and simulations, we address the following questions: (i) How token binding kinetics affects the current-density relation on the lattice; (ii) How this current-density relation depends on the scarcity of tokens; (iii) How tokens propagate the effects of the locally-imposed disorder (such as a slow site) over the entire lattice; (iv) How a shared pool of tokens couples concurrent TASEPs running on multiple lattices; (v) How our results translate to TASEPs with open boundaries that exchange particles with the reservoir. Since real particle motion (including in biological systems that inspired the standard TASEP model, e.g., protein synthesis or movement of molecular motors) is often catalyzed, regulated, actuated, or otherwise mediated, the token-driven TASEP dynamics analyzed in this paper should allow for a better understanding of real systems and enable a closer match between TASEP theory and experimental observations.","lang":"eng"}],"date_updated":"2025-09-30T12:44:54Z","day":"08","publisher":"Institute of Science and Technology Austria","_id":"19658","corr_author":"1","license":"https://creativecommons.org/licenses/by-sa/4.0/","oa":1,"date_created":"2025-05-08T05:43:38Z","status":"public","article_processing_charge":"No","department":[{"_id":"GaTk"}],"tmp":{"short":"CC BY-SA (4.0)","name":"Creative Commons Attribution-ShareAlike 4.0 International Public License (CC BY-SA 4.0)","image":"/images/cc_by_sa.png","legal_code_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode"},"year":"2025","month":"05","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","last_name":"Tkačik"}],"oa_version":"Published Version","file":[{"date_created":"2025-05-08T05:41:31Z","checksum":"5c15966e4139f10281ab03575f753f82","file_name":"pre_tasep_export_data.zip","creator":"gtkacik","file_id":"19659","access_level":"open_access","file_size":7387217,"relation":"main_file","success":1,"date_updated":"2025-05-08T05:41:31Z","content_type":"application/zip"},{"date_updated":"2025-05-12T07:36:23Z","content_type":"text/plain","checksum":"939a9341feee946a2399cab226fe69e8","file_name":"readme.txt","date_created":"2025-05-12T07:36:23Z","file_id":"19678","access_level":"open_access","creator":"gtkacik","file_size":587,"relation":"main_file"}]},{"project":[{"name":"Efficient coding with biophysical realism","_id":"626c45b5-2b32-11ec-9570-e509828c1ba6","grant_number":"P34015"},{"grant_number":"P28844-B27","call_identifier":"FWF","_id":"254E9036-B435-11E9-9278-68D0E5697425","name":"Biophysics of information processing in gene regulation"},{"_id":"7bfe6a29-9f16-11ee-852c-c0da5e2045d9","name":"Transcription in 4D: the dynamic interplay between chromatin architecture and gene expression in developing pseudo-embryos","grant_number":"101118866"}],"intvolume":"        54","author":[{"orcid":"0000-0002-6699-1455","last_name":"Tkačik","full_name":"Tkačik, Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper"},{"last_name":"Wolde","first_name":"Pieter Rein Ten","full_name":"Wolde, Pieter Rein Ten"}],"external_id":{"pmid":["39929539"],"isi":["001488641500013"]},"oa_version":"Published Version","file":[{"content_type":"application/pdf","date_updated":"2025-05-19T07:55:51Z","checksum":"9ab623b2bc45dcd5fdd2c9577ea8ae9f","file_name":"2025_AnnualReviewBiophysics_Tkacik.pdf","date_created":"2025-05-19T07:55:51Z","success":1,"file_size":317925,"relation":"main_file","file_id":"19710","access_level":"open_access","creator":"dernst"}],"publication_status":"published","page":"249-274","pmid":1,"article_type":"original","isi":1,"tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"department":[{"_id":"GaTk"}],"month":"05","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","quality_controlled":"1","year":"2025","publication_identifier":{"eissn":["1936-1238"]},"date_updated":"2025-09-30T12:33:33Z","abstract":[{"text":"Living systems are characterized by controlled flows of matter, energy, and information. While the biophysics community has productively engaged with the first two, addressing information flows has been more challenging, with some scattered success in evolutionary theory and a more coherent track record in neuroscience. Nevertheless, interdisciplinary work of the past two decades at the interface of biophysics, quantitative biology, and engineering has led to an emerging mathematical language for describing information flows at the molecular scale. This is where the central processes of life unfold: from detection and transduction of environmental signals to the readout or copying of genetic information and the triggering of adaptive cellular responses. Such processes are coordinated by complex biochemical reaction networks that operate at room temperature, are out of equilibrium, and use low copy numbers of diverse molecular species with limited interaction specificity. Here we review how flows of information through biochemical networks can be formalized using information-theoretic quantities, quantified from data, and computed within various modeling frameworks. Optimization of information flows is presented as a candidate design principle that navigates the relevant time, energy, crosstalk, and metabolic constraints to predict reliable cellular signaling and gene regulation architectures built of individually noisy components.","lang":"eng"}],"doi":"10.1146/annurev-biophys-060524-102720","file_date_updated":"2025-05-19T07:55:51Z","citation":{"chicago":"Tkačik, Gašper, and Pieter Rein Ten Wolde. “Information Processing in Biochemical Networks.” <i>Annual Review of Biophysics</i>. Annual Reviews, 2025. <a href=\"https://doi.org/10.1146/annurev-biophys-060524-102720\">https://doi.org/10.1146/annurev-biophys-060524-102720</a>.","apa":"Tkačik, G., &#38; Wolde, P. R. T. (2025). Information processing in biochemical networks. <i>Annual Review of Biophysics</i>. Annual Reviews. <a href=\"https://doi.org/10.1146/annurev-biophys-060524-102720\">https://doi.org/10.1146/annurev-biophys-060524-102720</a>","ista":"Tkačik G, Wolde PRT. 2025. Information processing in biochemical networks. Annual review of biophysics. 54, 249–274.","ama":"Tkačik G, Wolde PRT. Information processing in biochemical networks. <i>Annual review of biophysics</i>. 2025;54:249-274. doi:<a href=\"https://doi.org/10.1146/annurev-biophys-060524-102720\">10.1146/annurev-biophys-060524-102720</a>","ieee":"G. Tkačik and P. R. T. Wolde, “Information processing in biochemical networks,” <i>Annual review of biophysics</i>, vol. 54. Annual Reviews, pp. 249–274, 2025.","mla":"Tkačik, Gašper, and Pieter Rein Ten Wolde. “Information Processing in Biochemical Networks.” <i>Annual Review of Biophysics</i>, vol. 54, Annual Reviews, 2025, pp. 249–74, doi:<a href=\"https://doi.org/10.1146/annurev-biophys-060524-102720\">10.1146/annurev-biophys-060524-102720</a>.","short":"G. Tkačik, P.R.T. Wolde, Annual Review of Biophysics 54 (2025) 249–274."},"volume":54,"language":[{"iso":"eng"}],"article_processing_charge":"Yes (in subscription journal)","status":"public","acknowledgement":"G.T. acknowledges the support of the Human Frontiers Science Program (HFSP), the Austrian Science Fund (FWF 10.55776/P34015, 10.55776/P28844), and the European Research Council Synergy DYNATRANS (ERC-2023-SyG 101118866) grant. P.R.t.W. performed his work at the research institute AMOLF and acknowledges support from the Dutch Research Council (NWO) and funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement 885065).","_id":"19701","publisher":"Annual Reviews","day":"01","date_created":"2025-05-18T22:02:50Z","oa":1,"corr_author":"1","date_published":"2025-05-01T00:00:00Z","publication":"Annual review of biophysics","scopus_import":"1","type":"journal_article","OA_type":"hybrid","OA_place":"publisher","ddc":["570"],"title":"Information processing in biochemical networks","has_accepted_license":"1"},{"file":[{"content_type":"application/pdf","date_updated":"2025-11-24T08:25:19Z","date_created":"2025-11-24T08:25:19Z","file_name":"2025_MagneticResonance_Kapoor.pdf","checksum":"c63dd47b0e77f9451821436bb77d27c9","relation":"main_file","file_size":3081399,"success":1,"creator":"dernst","file_id":"20672","access_level":"open_access"}],"oa_version":"Published Version","page":"243-256","publication_status":"published","intvolume":"         6","project":[{"_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854","name":"IST Austria Open Access Fund"}],"author":[{"full_name":"Kapoor, Lucky","first_name":"Lucky","id":"84b9700b-15b2-11ec-abd3-831089e67615","last_name":"Kapoor","orcid":"0000-0001-8319-2148"},{"last_name":"Ruzickova","full_name":"Ruzickova, Natalia","first_name":"Natalia","id":"D2761128-D73D-11E9-A1BF-BA0DE6697425"},{"first_name":"Predrag","id":"68AA0E5A-AFDA-11E9-9994-141DE6697425","full_name":"Zivadinovic, Predrag","last_name":"Zivadinovic"},{"first_name":"Valentin","id":"4c665ce3-0016-11ec-bea0-e44de7a4fa3d","full_name":"Leitner, Valentin","last_name":"Leitner"},{"first_name":"Maria A","id":"44A03D04-AEA4-11E9-B225-EA2DE6697425","full_name":"Sisak, Maria A","last_name":"Sisak"},{"last_name":"Mweka","full_name":"Mweka, Cecelia N","first_name":"Cecelia N","id":"2a69ab4b-896a-11ed-bdf8-cb8641cf2b21"},{"last_name":"Dobbelaere","id":"c15a5412-de82-11ed-b809-8dc1aa996e40","first_name":"Jeroen A","full_name":"Dobbelaere, Jeroen A"},{"orcid":"0000-0001-8342-202X","last_name":"Katsaros","full_name":"Katsaros, Georgios","id":"38DB5788-F248-11E8-B48F-1D18A9856A87","first_name":"Georgios"},{"id":"7B541462-FAF6-11E9-A490-E8DFE5697425","first_name":"Paul","full_name":"Schanda, Paul","last_name":"Schanda","orcid":"0000-0002-9350-7606"}],"PlanS_conform":"1","issue":"2","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"11","year":"2025","quality_controlled":"1","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_type":"original","department":[{"_id":"JoFi"},{"_id":"GaTk"},{"_id":"JoCs"},{"_id":"EvBe"},{"_id":"TaHa"},{"_id":"GradSch"},{"_id":"GeKa"},{"_id":"PaSc"}],"article_processing_charge":"Yes","acknowledgement":"First and foremost, we are grateful to the conference organizers who have provided data, either in the form of tables or by pointing us to abstract books. We thank the reviewers and the handling editor (Gottfried Otting) for the careful reading and suggestions. This project emerged from an interactive course about energy and climate, held at IST Austria by Jeroen Dobbelaere, Georgios Katsaros and Paul Schanda. We are grateful to ISTA's Graduate School for enabling this interdisciplinary course and to all participating students. We thank the following persons for discussions and/or comments about the manuscript: Helene Van Melckebeke, Mei Hong, Jeff Hoch, Gottfried Otting and Matthias Ernst. For the preparation of the manuscript, AI tools have been used, namely for finding relevant literature (ChatGPT) and for correcting the text (Writefull, within Overleaf LaTeX).","status":"public","date_created":"2025-11-23T23:01:39Z","oa":1,"corr_author":"1","_id":"20664","publisher":"Copernicus Publications","day":"10","date_updated":"2026-06-10T08:45:11Z","abstract":[{"text":"Conference travel contributes to the climate footprint of academic research. Here, we provide a quantitative estimate of the carbon emissions associated with conference attendance by analyzing travel data from participants of 10 international conferences in the field of magnetic resonance, namely EUROMAR, ENC and ICMRBS. We find that attending a EUROMAR conference produces, on average, more than 1 t CO2 eq.. For the analyzed conferences outside Europe, the corresponding value is about 2–3 times higher, on average, with intercontinental trips amounting to up to 5 t. We compare these conference-related emissions to other activities associated with research and show that conference travel is a substantial portion of the total climate footprint of a researcher in magnetic resonance. We explore several strategies to reduce these emissions, including the impact of selecting conference venues more strategically and the possibility of decentralized conferences. Through a detailed comparison of train versus air travel – accounting for both direct and infrastructure-related emissions – we demonstrate that train travel offers considerable carbon savings. These data may provide a basis for strategic choices of future conferences in the field and for individuals deciding on their conference attendance.","lang":"eng"}],"publication_identifier":{"eissn":["2699-0016"]},"language":[{"iso":"eng"}],"volume":6,"doi":"10.5194/mr-6-243-2025","citation":{"ieee":"L. Kapoor <i>et al.</i>, “Quantifying the carbon footprint of conference travel: The case of NMR meetings,” <i>Magnetic Resonance</i>, vol. 6, no. 2. Copernicus Publications, pp. 243–256, 2025.","apa":"Kapoor, L., Ruzickova, N., Zivadinovic, P., Leitner, V., Sisak, M. A., Mweka, C. N., … Schanda, P. (2025). Quantifying the carbon footprint of conference travel: The case of NMR meetings. <i>Magnetic Resonance</i>. Copernicus Publications. <a href=\"https://doi.org/10.5194/mr-6-243-2025\">https://doi.org/10.5194/mr-6-243-2025</a>","chicago":"Kapoor, Lucky, Natalia Ruzickova, Predrag Zivadinovic, Valentin Leitner, Maria A Sisak, Cecelia N Mweka, Jeroen A Dobbelaere, Georgios Katsaros, and Paul Schanda. “Quantifying the Carbon Footprint of Conference Travel: The Case of NMR Meetings.” <i>Magnetic Resonance</i>. Copernicus Publications, 2025. <a href=\"https://doi.org/10.5194/mr-6-243-2025\">https://doi.org/10.5194/mr-6-243-2025</a>.","ista":"Kapoor L, Ruzickova N, Zivadinovic P, Leitner V, Sisak MA, Mweka CN, Dobbelaere JA, Katsaros G, Schanda P. 2025. Quantifying the carbon footprint of conference travel: The case of NMR meetings. Magnetic Resonance. 6(2), 243–256.","ama":"Kapoor L, Ruzickova N, Zivadinovic P, et al. Quantifying the carbon footprint of conference travel: The case of NMR meetings. <i>Magnetic Resonance</i>. 2025;6(2):243-256. doi:<a href=\"https://doi.org/10.5194/mr-6-243-2025\">10.5194/mr-6-243-2025</a>","short":"L. Kapoor, N. Ruzickova, P. Zivadinovic, V. Leitner, M.A. Sisak, C.N. Mweka, J.A. Dobbelaere, G. Katsaros, P. Schanda, Magnetic Resonance 6 (2025) 243–256.","mla":"Kapoor, Lucky, et al. “Quantifying the Carbon Footprint of Conference Travel: The Case of NMR Meetings.” <i>Magnetic Resonance</i>, vol. 6, no. 2, Copernicus Publications, 2025, pp. 243–56, doi:<a href=\"https://doi.org/10.5194/mr-6-243-2025\">10.5194/mr-6-243-2025</a>."},"file_date_updated":"2025-11-24T08:25:19Z","OA_type":"gold","APC_amount":"1260 EUR","title":"Quantifying the carbon footprint of conference travel: The case of NMR meetings","has_accepted_license":"1","DOAJ_listed":"1","OA_place":"publisher","ddc":["000"],"publication":"Magnetic Resonance","date_published":"2025-11-10T00:00:00Z","type":"journal_article","scopus_import":"1","related_material":{"link":[{"description":"News on ISTA website","relation":"research_data","url":"https://ista.ac.at/en/news/carbon-footprint-of-conference-travel/"}],"record":[{"relation":"research_data","id":"20242","status":"public"}]}},{"OA_place":"publisher","ddc":["616","576","614","519"],"has_accepted_license":"1","title":"Adaptive processes in biology and culture: Models of evolving vaccine resistance and the record statistics of innovation","date_published":"2025-12-15T00:00:00Z","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"18307"},{"status":"public","id":"9905","relation":"part_of_dissertation"}]},"type":"dissertation","article_processing_charge":"No","status":"public","_id":"20811","day":"15","publisher":"Institute of Science and Technology Austria","oa":1,"date_created":"2025-12-12T14:39:56Z","corr_author":"1","publication_identifier":{"issn":["2663-337X"]},"date_updated":"2026-07-29T12:57:49Z","abstract":[{"text":"\tThis thesis is organized into two parts, each comprising two chapters: Chapter 1 and 2 offer models for the evolution of vaccine resistance in response to diverse vaccination strategies. Chapter 3 and 4 review the statistics of records, their connection to models of innovation and an application to the cultural evolution of sports.\r\n\tIn chapter 1 we present a modelling study from 2021 on the evolution of SARS-CoV-2. At that time the vaccine-resistant Omicron variant had not yet evolved. In our model we consider a population that is becoming vaccinated over time, while a pathogen is spreading in the population and eventually becoming resistant to the vaccine. We explore effective pharmaceutical and non-pharmaceutical interventions to prevent the emergence of vaccine resistance. \r\n\tIn chapter 2 we model a particular set of complex vaccination strategies, mosaic and pyramid vaccination, where an immunologically diverse portfolio of vaccines is considered. We find that a bet-hatching strategy, in which vaccine types are distributed in the population, is effective at hindering the evolution of vaccine resistance if mutation rates are high. \r\n\tIn chapter 3 we switch gears and present a review on the statistics of records. We highlight similarities and analogies to other models in the fields of statistical physics, evolution and innovation. This offers interesting complimentary perspectives on well-known models. \r\n\tIn chapter 4 we apply models of record statistics and innovation to study cultural evolution in sport. We propose a model of sport evolution that combines deterministic improvements in performance and stochastic bursts of improvements due to innovation. ","lang":"eng"}],"file_date_updated":"2025-12-16T21:52:19Z","citation":{"mla":"Rella, Simon. <i>Adaptive Processes in Biology and Culture: Models of Evolving Vaccine Resistance and the Record Statistics of Innovation</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20811\">10.15479/AT-ISTA-20811</a>.","short":"S. Rella, Adaptive Processes in Biology and Culture: Models of Evolving Vaccine Resistance and the Record Statistics of Innovation, Institute of Science and Technology Austria, 2025.","apa":"Rella, S. (2025). <i>Adaptive processes in biology and culture: Models of evolving vaccine resistance and the record statistics of innovation</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-20811\">https://doi.org/10.15479/AT-ISTA-20811</a>","chicago":"Rella, Simon. “Adaptive Processes in Biology and Culture: Models of Evolving Vaccine Resistance and the Record Statistics of Innovation.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-20811\">https://doi.org/10.15479/AT-ISTA-20811</a>.","ama":"Rella S. Adaptive processes in biology and culture: Models of evolving vaccine resistance and the record statistics of innovation. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20811\">10.15479/AT-ISTA-20811</a>","ista":"Rella S. 2025. Adaptive processes in biology and culture: Models of evolving vaccine resistance and the record statistics of innovation. Institute of Science and Technology Austria.","ieee":"S. Rella, “Adaptive processes in biology and culture: Models of evolving vaccine resistance and the record statistics of innovation,” Institute of Science and Technology Austria, 2025."},"doi":"10.15479/AT-ISTA-20811","language":[{"iso":"eng"}],"month":"12","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","year":"2025","supervisor":[{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","full_name":"Tkačik, Gašper","orcid":"0000-0002-6699-1455","last_name":"Tkačik"},{"orcid":"0000-0001-8243-4694","last_name":"Kondrashov","full_name":"Kondrashov, Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","first_name":"Fyodor"}],"doi_confirm":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)"},"alternative_title":["ISTA Thesis"],"department":[{"_id":"GradSch"},{"_id":"GaTk"},{"_id":"FyKo"}],"oa_version":"Published Version","file":[{"date_updated":"2025-12-16T21:49:52Z","content_type":"application/pdf","date_created":"2025-12-16T21:49:52Z","file_name":"2025_Rella_Simon_Thesis.pdf","checksum":"a0bd7a585720e60df284101b8afdf6bb","creator":"srella","access_level":"open_access","file_id":"20831","relation":"main_file","file_size":29019662,"success":1},{"file_size":42094025,"relation":"source_file","access_level":"open_access","file_id":"20832","creator":"srella","checksum":"b8b3a90932ae1d96d307838710f46e32","file_name":"2025_Rella_Simon_Thesis_Sourcefiles.zip","date_created":"2025-12-16T21:52:19Z","content_type":"application/zip","date_updated":"2025-12-16T21:52:19Z"}],"degree_awarded":"PhD","publication_status":"published","page":"95","author":[{"last_name":"Rella","id":"B4765ACA-AA38-11E9-AC9A-0930E6697425","first_name":"Simon","full_name":"Rella, Simon"}]},{"intvolume":"       111","external_id":{"isi":["001496415600007"]},"author":[{"first_name":"Bor","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","full_name":"Kavcic, Bor","last_name":"Kavcic","orcid":"0000-0001-6041-254X"},{"first_name":"Gašper","id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","full_name":"Tkačik, Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455"}],"file":[{"content_type":"application/pdf","date_updated":"2025-06-03T09:18:20Z","date_created":"2025-06-03T09:18:20Z","checksum":"e8851ccd7cd0525c08c7308710413e74","file_name":"2025_PhysRevE_Kavcic.pdf","file_size":2766143,"relation":"main_file","success":1,"creator":"dernst","access_level":"open_access","file_id":"19787"}],"oa_version":"Published Version","publication_status":"published","tmp":{"image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"isi":1,"article_type":"original","article_number":"054122","department":[{"_id":"GaTk"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","issue":"5","month":"05","year":"2025","quality_controlled":"1","abstract":[{"lang":"eng","text":"We consider a family of totally asymmetric simple exclusion processes (TASEPs), consisting of particles on a lattice that require binding by a “token” in various physical configurations to advance over the lattice. Using a combination of theory and simulations, we address the following questions: (i) How does token binding kinetics affect the current-density relation on the lattice? (ii) How does this current-density relation depend on the scarcity of tokens? (iii) How do tokens propagate the effects of the locally imposed disorder (such as a slow site) over the entire lattice? (iv) How does a shared pool of tokens couple concurrent TASEPs running on multiple lattices? and (v) How do our results translate to TASEPs with open boundaries that exchange particles with the reservoir? Since real particle motion (including in biological systems that inspired the standard TASEP model, e.g., protein synthesis or movement of molecular motors) is often catalyzed, regulated, actuated, or otherwise mediated, the token-driven TASEP dynamics analyzed in this paper should allow for a better understanding of real systems and enable a closer match between TASEP theory and experimental observations."}],"date_updated":"2026-08-04T08:34:22Z","publication_identifier":{"eissn":["2470-0053"],"issn":["2470-0045"]},"language":[{"iso":"eng"}],"volume":111,"file_date_updated":"2025-06-03T09:18:20Z","doi":"10.1103/physreve.111.054122","citation":{"ieee":"B. Kavcic and G. Tkačik, “Token-driven totally asymmetric simple exclusion processes,” <i>Physical Review E</i>, vol. 111, no. 5. American Physical Society, 2025.","ama":"Kavcic B, Tkačik G. Token-driven totally asymmetric simple exclusion processes. <i>Physical Review E</i>. 2025;111(5). doi:<a href=\"https://doi.org/10.1103/physreve.111.054122\">10.1103/physreve.111.054122</a>","ista":"Kavcic B, Tkačik G. 2025. Token-driven totally asymmetric simple exclusion processes. Physical Review E. 111(5), 054122.","apa":"Kavcic, B., &#38; Tkačik, G. (2025). Token-driven totally asymmetric simple exclusion processes. <i>Physical Review E</i>. American Physical Society. <a href=\"https://doi.org/10.1103/physreve.111.054122\">https://doi.org/10.1103/physreve.111.054122</a>","chicago":"Kavcic, Bor, and Gašper Tkačik. “Token-Driven Totally Asymmetric Simple Exclusion Processes.” <i>Physical Review E</i>. American Physical Society, 2025. <a href=\"https://doi.org/10.1103/physreve.111.054122\">https://doi.org/10.1103/physreve.111.054122</a>.","short":"B. Kavcic, G. Tkačik, Physical Review E 111 (2025).","mla":"Kavcic, Bor, and Gašper Tkačik. “Token-Driven Totally Asymmetric Simple Exclusion Processes.” <i>Physical Review E</i>, vol. 111, no. 5, 054122, American Physical Society, 2025, doi:<a href=\"https://doi.org/10.1103/physreve.111.054122\">10.1103/physreve.111.054122</a>."},"acknowledgement":"B.K. thanks Stefano Elefante, Simon Rella, and Michal Hledík for their help with the usage of the cluster. B.K. additionally thanks Călin Guet and his group for help and advice. We thank M. Hennessey-Wesen and Luca Ciandrini for constructive comments on the paper. We thank Ankita Gupta (Indian Institute of Technology) for spotting a typographical error in Eq. (50) in the preprint version of this paper.","status":"public","article_processing_charge":"Yes (via OA deal)","corr_author":"1","date_created":"2025-06-03T09:01:55Z","oa":1,"publisher":"American Physical Society","day":"19","_id":"19785","publication":"Physical Review E","date_published":"2025-05-19T00:00:00Z","type":"journal_article","scopus_import":"1","related_material":{"record":[{"status":"public","relation":"research_data","id":"19658"},{"status":"public","id":"10579","relation":"earlier_version"}]},"OA_type":"hybrid","title":"Token-driven totally asymmetric simple exclusion processes","has_accepted_license":"1","ddc":["570"],"OA_place":"publisher"},{"date_published":"2025-09-15T00:00:00Z","type":"dissertation","related_material":{"record":[{"status":"public","id":"18525","relation":"part_of_dissertation"}]},"title":"Effect propagation in biological networks","has_accepted_license":"1","OA_place":"publisher","ddc":["570","530"],"date_updated":"2026-08-07T10:58:50Z","publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-066-4"]},"language":[{"iso":"eng"}],"citation":{"chicago":"Ruzickova, Natalia. “Effect Propagation in Biological Networks.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-20357\">https://doi.org/10.15479/AT-ISTA-20357</a>.","apa":"Ruzickova, N. (2025). <i>Effect propagation in biological networks</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-20357\">https://doi.org/10.15479/AT-ISTA-20357</a>","ama":"Ruzickova N. Effect propagation in biological networks. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20357\">10.15479/AT-ISTA-20357</a>","ista":"Ruzickova N. 2025. Effect propagation in biological networks. Institute of Science and Technology Austria.","ieee":"N. Ruzickova, “Effect propagation in biological networks,” Institute of Science and Technology Austria, 2025.","mla":"Ruzickova, Natalia. <i>Effect Propagation in Biological Networks</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20357\">10.15479/AT-ISTA-20357</a>.","short":"N. Ruzickova, Effect Propagation in Biological Networks, Institute of Science and Technology Austria, 2025."},"doi":"10.15479/AT-ISTA-20357","file_date_updated":"2026-08-07T10:57:34Z","article_processing_charge":"No","acknowledgement":"I would also like to acknowledge the Austrian Academy of Sciences for funding through the\r\nDOC Fellowship program (fellowship number 26917), the Grants Office at ISTA for their\r\nassistance with the application, and the Scientific Computing Unit for their support regarding\r\nhigh-performance computation.\r\n","status":"public","date_created":"2025-09-15T17:04:48Z","corr_author":"1","_id":"20357","day":"15","publisher":"Institute of Science and Technology Austria","doi_confirm":"1","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"E-Lib"}],"supervisor":[{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","first_name":"Gašper","full_name":"Tkačik, Gašper","last_name":"Tkačik","orcid":"0000-0002-6699-1455"}],"department":[{"_id":"GradSch"},{"_id":"GaTk"}],"alternative_title":["ISTA Thesis"],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","month":"09","keyword":["gene regulation","networks","omnigenic model","pancreas","collective behaviour"],"year":"2025","project":[{"name":"Collective behaviour of cells in pancreatic Islets of Langerhans","_id":"7bec9174-9f16-11ee-852c-ded9fe5f810e"}],"author":[{"id":"D2761128-D73D-11E9-A1BF-BA0DE6697425","first_name":"Natalia","full_name":"Ruzickova, Natalia","last_name":"Ruzickova"}],"file":[{"date_created":"2026-08-07T10:57:05Z","file_name":"2025_Ruzickova_Natalia_Thesis.zip","checksum":"0582508d439b233497384f83a8307398","creator":"cchlebak","access_level":"closed","file_id":"22661","relation":"source_file","file_size":56464803,"date_updated":"2026-08-07T10:57:05Z","content_type":"application/x-zip-compressed"},{"content_type":"application/pdf","embargo_to":"open_access","date_updated":"2026-08-07T10:57:34Z","date_created":"2026-08-07T10:57:34Z","embargo":"2026-09-15","checksum":"b722289fd550abede63adc27b9c61784","file_name":"2025_Ruzickova_Natalia_Thesis.pdf","relation":"main_file","file_size":30634378,"creator":"cchlebak","access_level":"closed","file_id":"22662"}],"oa_version":"Published Version","page":"160","publication_status":"published","degree_awarded":"PhD"}]