[{"author":[{"first_name":"Fabrizio","last_name":"Olmeda","full_name":"Olmeda, Fabrizio","id":"69dbf5fb-8a76-11ed-866b-fb486d8b5689"},{"full_name":"Gupta, Misha","last_name":"Gupta","first_name":"Misha"},{"full_name":"Bektas, Onurcan","first_name":"Onurcan","last_name":"Bektas"},{"full_name":"Rulands, Steffen","first_name":"Steffen","last_name":"Rulands"}],"day":"09","ddc":["570"],"project":[{"name":"IST-BRIDGE: International postdoctoral program","_id":"fc2ed2f7-9c52-11eb-aca3-c01059dda49c","call_identifier":"H2020","grant_number":"101034413"}],"publication_identifier":{"eissn":["2835-8279"]},"ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"publication":"PRX Life","PlanS_conform":"1","article_processing_charge":"Yes","license":"https://creativecommons.org/licenses/by/4.0/","file":[{"date_updated":"2026-02-24T06:53:05Z","date_created":"2026-02-24T06:53:05Z","file_name":"2026_PRXLife_Olmeda.pdf","creator":"dernst","file_id":"21351","access_level":"open_access","success":1,"file_size":5857833,"checksum":"df9776422862d1d02c66d98e2d620849","content_type":"application/pdf","relation":"main_file"}],"year":"2026","publication_status":"published","intvolume":"         4","article_number":"013018","OA_type":"gold","corr_author":"1","file_date_updated":"2026-02-24T06:53:05Z","citation":{"chicago":"Olmeda, Fabrizio, Misha Gupta, Onurcan Bektas, and Steffen Rulands. “Spatiotemporal Patterns of Active Epigenetic Turnover.” <i>PRX Life</i>. American Physical Society, 2026. <a href=\"https://doi.org/10.1103/89bj-79g5\">https://doi.org/10.1103/89bj-79g5</a>.","mla":"Olmeda, Fabrizio, et al. “Spatiotemporal Patterns of Active Epigenetic Turnover.” <i>PRX Life</i>, vol. 4, 013018, American Physical Society, 2026, doi:<a href=\"https://doi.org/10.1103/89bj-79g5\">10.1103/89bj-79g5</a>.","ieee":"F. Olmeda, M. Gupta, O. Bektas, and S. Rulands, “Spatiotemporal patterns of active epigenetic turnover,” <i>PRX Life</i>, vol. 4. American Physical Society, 2026.","short":"F. Olmeda, M. Gupta, O. Bektas, S. Rulands, PRX Life 4 (2026).","apa":"Olmeda, F., Gupta, M., Bektas, O., &#38; Rulands, S. (2026). Spatiotemporal patterns of active epigenetic turnover. <i>PRX Life</i>. American Physical Society. <a href=\"https://doi.org/10.1103/89bj-79g5\">https://doi.org/10.1103/89bj-79g5</a>","ista":"Olmeda F, Gupta M, Bektas O, Rulands S. 2026. Spatiotemporal patterns of active epigenetic turnover. PRX Life. 4, 013018.","ama":"Olmeda F, Gupta M, Bektas O, Rulands S. Spatiotemporal patterns of active epigenetic turnover. <i>PRX Life</i>. 2026;4. doi:<a href=\"https://doi.org/10.1103/89bj-79g5\">10.1103/89bj-79g5</a>"},"OA_place":"publisher","title":"Spatiotemporal patterns of active epigenetic turnover","type":"journal_article","has_accepted_license":"1","date_published":"2026-02-09T00:00:00Z","quality_controlled":"1","department":[{"_id":"EdHa"}],"publisher":"American Physical Society","abstract":[{"text":"DNA methylation is a primary layer of epigenetic modification that plays a pivotal role in the regulation of development, aging, and cancer. The concurrent activity of opposing enzymes that mediate DNA methylation and demethylation gives rise to a biochemical cycle and active turnover of DNA methylation. While the ensuing biochemical oscillations have been implicated in the regulation of cell differentiation, their functional role and spatiotemporal dynamics are unknown. In this work, we demonstrate that chromatin-mediated coupling between these local biochemical cycles can lead to the emergence of phase-locked domains, regions of locally synchronized turnover activity, whose coarsening is arrested by genomic heterogeneity. We introduce a minimal model based on stochastic oscillators with constrained long-range and nonreciprocal interactions, shaped by the local chromatin organization. Through a combination of analytical theory and stochastic simulations, we predict both the degree of synchronization and the typical size of emergent phase-locked domains. We qualitatively test these predictions using single-cell sequencing data. Our results show that DNA methylation turnover exhibits surprisingly rich spatiotemporal patterns that may be used by cells to control cell differentiation.","lang":"eng"}],"oa_version":"Published Version","acknowledgement":"This project has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 950349 and the Marie Skłodowska-Curie Grant Agreement No. 101034413. The computations in this paper were run in part on the the FASRC Cannon cluster supported by the FAS Division of Science Research Computing Group at Harvard University and the cluster of the Max Planck Institute for the Physics of Complex Systems.","month":"02","DOAJ_listed":"1","status":"public","_id":"21275","doi":"10.1103/89bj-79g5","date_updated":"2026-02-24T06:54:32Z","volume":4,"date_created":"2026-02-17T08:17:53Z","article_type":"original","language":[{"iso":"eng"}],"oa":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"ddc":["570"],"project":[{"name":"IST-BRIDGE: International postdoctoral program","_id":"fc2ed2f7-9c52-11eb-aca3-c01059dda49c","call_identifier":"H2020","grant_number":"101034413"}],"publication_identifier":{"issn":["1745-2473"],"eissn":["1745-2481"]},"day":"29","author":[{"full_name":"Olmeda, Fabrizio","id":"69dbf5fb-8a76-11ed-866b-fb486d8b5689","last_name":"Olmeda","first_name":"Fabrizio"},{"full_name":"Lohoff, Tim","first_name":"Tim","last_name":"Lohoff"},{"full_name":"Kafetzopoulos, Ioannis","last_name":"Kafetzopoulos","first_name":"Ioannis"},{"first_name":"Stephen J.","last_name":"Clark","full_name":"Clark, Stephen J."},{"full_name":"Benson, Laura","first_name":"Laura","last_name":"Benson"},{"full_name":"Santos, Fatima","first_name":"Fatima","last_name":"Santos"},{"first_name":"Felix","last_name":"Krueger","full_name":"Krueger, Felix"},{"full_name":"Walker, Simon","first_name":"Simon","last_name":"Walker"},{"full_name":"Reik, Wolf","last_name":"Reik","first_name":"Wolf"},{"last_name":"Rulands","first_name":"Steffen","full_name":"Rulands, Steffen"}],"OA_type":"hybrid","year":"2026","publication_status":"epub_ahead","article_processing_charge":"Yes (via OA deal)","publication":"Nature Physics","PlanS_conform":"1","scopus_import":"1","publisher":"Springer Nature","abstract":[{"text":"The development of complex tissues relies on the precise assignment of cell identity. At the molecular scale, this process depends on the deposition of epigenetic modifications—such as methylation—that are regulated by complex biochemical networks and occur at specific regions on the DNA and chromatin. Here we show that despite the complexity of epigenetic regulation, dynamical scaling and self-similarity of DNA methylation marks emerge in embryonic development. Drawing on single-cell multi-omics experiments, super-resolution microscopy and statistical physics, we demonstrate that these phenomena originate in dynamical feedback between DNA methylation and the formation of nanoscale dynamic chromatin aggregates. These nanoscale processes lead to genome-wide increase in DNA methylation marks following a power law and self-similar correlation functions. Using this framework, we identify methylation patterns that precede gene expression changes in embryonic symmetry breaking. Our work identifies linear sequencing measurements as a laboratory to study mesoscopic biophysical processes in vivo.","lang":"eng"}],"quality_controlled":"1","department":[{"_id":"EdHa"}],"has_accepted_license":"1","date_published":"2026-04-29T00:00:00Z","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41567-026-03263-x"}],"title":"Scaling and self-similarity in the formation of the embryonic epigenome","type":"journal_article","OA_place":"publisher","citation":{"ama":"Olmeda F, Lohoff T, Kafetzopoulos I, et al. Scaling and self-similarity in the formation of the embryonic epigenome. <i>Nature Physics</i>. 2026. doi:<a href=\"https://doi.org/10.1038/s41567-026-03263-x\">10.1038/s41567-026-03263-x</a>","ista":"Olmeda F, Lohoff T, Kafetzopoulos I, Clark SJ, Benson L, Santos F, Krueger F, Walker S, Reik W, Rulands S. 2026. Scaling and self-similarity in the formation of the embryonic epigenome. Nature Physics.","short":"F. Olmeda, T. Lohoff, I. Kafetzopoulos, S.J. Clark, L. Benson, F. Santos, F. Krueger, S. Walker, W. Reik, S. Rulands, Nature Physics (2026).","mla":"Olmeda, Fabrizio, et al. “Scaling and Self-Similarity in the Formation of the Embryonic Epigenome.” <i>Nature Physics</i>, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41567-026-03263-x\">10.1038/s41567-026-03263-x</a>.","ieee":"F. Olmeda <i>et al.</i>, “Scaling and self-similarity in the formation of the embryonic epigenome,” <i>Nature Physics</i>. Springer Nature, 2026.","apa":"Olmeda, F., Lohoff, T., Kafetzopoulos, I., Clark, S. J., Benson, L., Santos, F., … Rulands, S. (2026). Scaling and self-similarity in the formation of the embryonic epigenome. <i>Nature Physics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41567-026-03263-x\">https://doi.org/10.1038/s41567-026-03263-x</a>","chicago":"Olmeda, Fabrizio, Tim Lohoff, Ioannis Kafetzopoulos, Stephen J. Clark, Laura Benson, Fatima Santos, Felix Krueger, Simon Walker, Wolf Reik, and Steffen Rulands. “Scaling and Self-Similarity in the Formation of the Embryonic Epigenome.” <i>Nature Physics</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41567-026-03263-x\">https://doi.org/10.1038/s41567-026-03263-x</a>."},"language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"article_type":"original","date_updated":"2026-05-11T06:22:47Z","date_created":"2026-05-10T22:02:16Z","status":"public","doi":"10.1038/s41567-026-03263-x","_id":"21849","month":"04","acknowledgement":"We thank all members of the W.R. and S.R. laboratories, F. Piazza, B. D. Simons, and F. Jülicher for helpful discussions. We thank M. Ciarchi for providing annotations for the chromatin compartments. S.R. is a member of the Center for Nano Science (CeNS). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement number 950349). Research in W.R.’s laboratory was supported by the Biotechnology and Biological Sciences Research Council (BB/K010867/1), Wellcome (095645/Z/11/Z) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (EpiCell lineage 882798). F.O. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement number 101034413. Open access funding provided by Max Planck Society.","oa_version":"Published Version"},{"publication_status":"published","year":"2025","intvolume":"        37","OA_type":"hybrid","article_number":"044122","file_date_updated":"2025-05-12T09:31:22Z","scopus_import":"1","publication":"Physics of Fluids","external_id":{"arxiv":["2501.00536"],"isi":["001482986200001"]},"article_processing_charge":"Yes (in subscription journal)","file":[{"file_size":4926853,"success":1,"checksum":"242d05898aa0a2348b9c108747adb5ce","content_type":"application/pdf","relation":"main_file","date_created":"2025-05-12T09:31:22Z","date_updated":"2025-05-12T09:31:22Z","file_name":"2025_PhysicsFluids_Bartolucci.pdf","creator":"dernst","file_id":"19681","access_level":"open_access"}],"publication_identifier":{"eissn":["1089-7666"],"issn":["1070-6631"]},"ddc":["530"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"author":[{"full_name":"Bartolucci, G.","last_name":"Bartolucci","first_name":"G."},{"first_name":"D. M.","last_name":"Busiello","full_name":"Busiello, D. M."},{"full_name":"Ciarchi, M.","first_name":"M.","last_name":"Ciarchi"},{"full_name":"Corticelli, A.","first_name":"A.","last_name":"Corticelli"},{"first_name":"I.","last_name":"Di Terlizzi","full_name":"Di Terlizzi, I."},{"id":"69dbf5fb-8a76-11ed-866b-fb486d8b5689","full_name":"Olmeda, Fabrizio","last_name":"Olmeda","first_name":"Fabrizio"},{"first_name":"D.","last_name":"Revignas","full_name":"Revignas, D."},{"last_name":"Schimmenti","first_name":"V. M.","full_name":"Schimmenti, V. M."}],"related_material":{"link":[{"description":"News on ISTA","url":"https://ista.ac.at/en/news/2025-ig-nobel-prize-for-perfect-pasta-sauce/","relation":"press_release"}]},"day":"01","_id":"19670","doi":"10.1063/5.0255841","status":"public","isi":1,"date_created":"2025-05-11T22:02:40Z","volume":37,"date_updated":"2026-04-28T13:24:53Z","article_type":"original","oa":1,"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","language":[{"iso":"eng"}],"issue":"4","oa_version":"Published Version","acknowledgement":"he authors thank Frank Jülicher, for supporting the initiative and stimulating discussions. We thank Tetsuya Spippayashi for enlightening clarifications on the historical origins of Cacio e pepe and Giuseppe Ricchitelli for helping with the construction of the experimental apparatus. We further thank Martina Gaiba, Alessandro Gaiba, John D. Treado, Virginia Lepore, Eleonora Nanu, Julia Kirsch, Lara Koehler, Burak Budanur, Irina Pi-Jaumà, Elizabeth Brückner, M.J. Franco Oñate, Giorgio Nicoletti, and Marco Salvalaglio for their support and for eating up the sample leftovers. Finally, we thank Simone Frau for taking the photograph in Fig. 1(a).","month":"04","date_published":"2025-04-01T00:00:00Z","has_accepted_license":"1","department":[{"_id":"EdHa"}],"quality_controlled":"1","abstract":[{"text":"“Pasta alla Cacio e pepe” is a traditional Italian dish made with pasta, pecorino cheese, and pepper. Despite its simple ingredient list, achieving the perfect texture and creaminess of the sauce can be challenging. In this study, we systematically explore the phase behavior of Cacio e pepe sauce, focusing on its stability at increasing temperatures for various proportions of cheese, water, and starch. We identify starch concentration as the key factor influencing sauce stability, with direct implications for practical cooking. Specifically, we delineate a regime where starch concentrations below 1% (relative to cheese mass) lead to the formation of system-wide clumps, a condition determining what we term the “Mozzarella Phase” and corresponding to an unpleasant and separated sauce. Additionally, we examine the impact of cheese concentration relative to water at a fixed starch level, observing a lower critical solution temperature that we theoretically rationalized by means of a minimal effective free-energy model. We further analyze the effect of a less traditional stabilizer, trisodium citrate, and observe a sharp transition from the Mozzarella Phase to a completely smooth and stable sauce, in contrast to starch-stabilized mixtures, where the transition is more gradual. Finally, we present a scientifically optimized recipe based on our findings, enabling a consistently flawless execution of this classic dish.","lang":"eng"}],"publisher":"AIP Publishing","citation":{"ista":"Bartolucci G, Busiello DM, Ciarchi M, Corticelli A, Di Terlizzi I, Olmeda F, Revignas D, Schimmenti VM. 2025. Phase behavior of Cacio e Pepe sauce. Physics of Fluids. 37(4), 044122.","ama":"Bartolucci G, Busiello DM, Ciarchi M, et al. Phase behavior of Cacio e Pepe sauce. <i>Physics of Fluids</i>. 2025;37(4). doi:<a href=\"https://doi.org/10.1063/5.0255841\">10.1063/5.0255841</a>","chicago":"Bartolucci, G., D. M. Busiello, M. Ciarchi, A. Corticelli, I. Di Terlizzi, Fabrizio Olmeda, D. Revignas, and V. M. Schimmenti. “Phase Behavior of Cacio e Pepe Sauce.” <i>Physics of Fluids</i>. AIP Publishing, 2025. <a href=\"https://doi.org/10.1063/5.0255841\">https://doi.org/10.1063/5.0255841</a>.","mla":"Bartolucci, G., et al. “Phase Behavior of Cacio e Pepe Sauce.” <i>Physics of Fluids</i>, vol. 37, no. 4, 044122, AIP Publishing, 2025, doi:<a href=\"https://doi.org/10.1063/5.0255841\">10.1063/5.0255841</a>.","apa":"Bartolucci, G., Busiello, D. M., Ciarchi, M., Corticelli, A., Di Terlizzi, I., Olmeda, F., … Schimmenti, V. M. (2025). Phase behavior of Cacio e Pepe sauce. <i>Physics of Fluids</i>. AIP Publishing. <a href=\"https://doi.org/10.1063/5.0255841\">https://doi.org/10.1063/5.0255841</a>","ieee":"G. Bartolucci <i>et al.</i>, “Phase behavior of Cacio e Pepe sauce,” <i>Physics of Fluids</i>, vol. 37, no. 4. AIP Publishing, 2025.","short":"G. Bartolucci, D.M. Busiello, M. Ciarchi, A. Corticelli, I. Di Terlizzi, F. Olmeda, D. Revignas, V.M. Schimmenti, Physics of Fluids 37 (2025)."},"OA_place":"publisher","arxiv":1,"type":"journal_article","title":"Phase behavior of Cacio e Pepe sauce"},{"publication_status":"published","year":"2024","intvolume":"       110","corr_author":"1","article_number":"024404","file_date_updated":"2024-09-11T05:59:36Z","scopus_import":"1","publication":"Physical Review E","external_id":{"isi":["001299670100004"],"pmid":["39294986"]},"article_processing_charge":"Yes (in subscription journal)","file":[{"checksum":"67fc2cc8eee3155e5c3b7380307d8284","success":1,"file_size":445696,"relation":"main_file","content_type":"application/pdf","file_name":"2024_PhysReviewE_Olmeda.pdf","creator":"dernst","date_updated":"2024-09-11T05:59:36Z","date_created":"2024-09-11T05:59:36Z","access_level":"open_access","file_id":"18053"}],"publication_identifier":{"issn":["2470-0045"],"eissn":["2470-0053"]},"project":[{"call_identifier":"H2020","_id":"fc2ed2f7-9c52-11eb-aca3-c01059dda49c","grant_number":"101034413","name":"IST-BRIDGE: International postdoctoral program"}],"ddc":["530"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"ec_funded":1,"author":[{"id":"69dbf5fb-8a76-11ed-866b-fb486d8b5689","full_name":"Olmeda, Fabrizio","last_name":"Olmeda","first_name":"Fabrizio"},{"full_name":"Rulands, Steffen","last_name":"Rulands","first_name":"Steffen"}],"pmid":1,"day":"01","_id":"17892","doi":"10.1103/PhysRevE.110.024404","status":"public","isi":1,"date_created":"2024-09-08T22:01:12Z","volume":110,"date_updated":"2025-09-08T09:17:18Z","article_type":"original","oa":1,"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","language":[{"iso":"eng"}],"issue":"2","acknowledgement":"We thank F. Piazza, M. Henkel, and F. Jülicher for helpful feedback and the entire Rulands group for fruitful discussions. We thank W. Reik, S. Clark, T. Lohoff, and I. Kafetzopoulos for fruitful discussions about the biological aspects of this work. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant No. 950349). This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant No. 101034413.","oa_version":"Published Version","month":"08","date_published":"2024-08-01T00:00:00Z","has_accepted_license":"1","department":[{"_id":"EdHa"}],"quality_controlled":"1","abstract":[{"text":"Enzyme-substrate kinetics form the basis of many biomolecular processes. The interplay between substrate binding and substrate geometry can give rise to long-range interactions between enzyme binding events. Here we study a general model of enzyme-substrate kinetics with restricted long-range interactions described by an exponent −𝛾. We employ a coherent-state path integral and renormalization group approach to calculate the first moment and two-point correlation function of the enzyme-binding profile. We show that starting from an empty substrate the average occupancy follows a power law with an exponent 1/(1−𝛾) over time. The correlation function decays algebraically with two distinct spatial regimes characterized by exponents −𝛾 on short distances and −(2/3)⁢(2−𝛾) on long distances. The crossover between both regimes scales inversely with the average substrate occupancy. Our work allows associating experimental measurements of bound enzyme locations with their binding kinetics and the spatial conformation of the substrate.","lang":"eng"}],"publisher":"American Physical Society","citation":{"mla":"Olmeda, Fabrizio, and Steffen Rulands. “Field Theory of Enzyme-Substrate Systems with Restricted Long-Range Interactions.” <i>Physical Review E</i>, vol. 110, no. 2, 024404, American Physical Society, 2024, doi:<a href=\"https://doi.org/10.1103/PhysRevE.110.024404\">10.1103/PhysRevE.110.024404</a>.","short":"F. Olmeda, S. Rulands, Physical Review E 110 (2024).","apa":"Olmeda, F., &#38; Rulands, S. (2024). Field theory of enzyme-substrate systems with restricted long-range interactions. <i>Physical Review E</i>. American Physical Society. <a href=\"https://doi.org/10.1103/PhysRevE.110.024404\">https://doi.org/10.1103/PhysRevE.110.024404</a>","ieee":"F. Olmeda and S. Rulands, “Field theory of enzyme-substrate systems with restricted long-range interactions,” <i>Physical Review E</i>, vol. 110, no. 2. American Physical Society, 2024.","chicago":"Olmeda, Fabrizio, and Steffen Rulands. “Field Theory of Enzyme-Substrate Systems with Restricted Long-Range Interactions.” <i>Physical Review E</i>. American Physical Society, 2024. <a href=\"https://doi.org/10.1103/PhysRevE.110.024404\">https://doi.org/10.1103/PhysRevE.110.024404</a>.","ama":"Olmeda F, Rulands S. Field theory of enzyme-substrate systems with restricted long-range interactions. <i>Physical Review E</i>. 2024;110(2). doi:<a href=\"https://doi.org/10.1103/PhysRevE.110.024404\">10.1103/PhysRevE.110.024404</a>","ista":"Olmeda F, Rulands S. 2024. Field theory of enzyme-substrate systems with restricted long-range interactions. Physical Review E. 110(2), 024404."},"type":"journal_article","title":"Field theory of enzyme-substrate systems with restricted long-range interactions"}]