[{"publication_identifier":{"eissn":["20411723"]},"publication_status":"published","file":[{"creator":"dernst","file_size":1191827,"date_updated":"2020-07-14T12:47:31Z","file_name":"2019_NatureComm_Chassin.pdf","date_created":"2019-05-20T07:33:54Z","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_id":"6471","checksum":"e214d3e4f8c81e35981583c4569b51b8"}],"language":[{"iso":"eng"}],"issue":"1","volume":10,"related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1038/s41467-023-36111-0"}]},"license":"https://creativecommons.org/licenses/by/4.0/","abstract":[{"text":"Tight control over protein degradation is a fundamental requirement for cells to respond rapidly to various stimuli and adapt to a fluctuating environment. Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons) for the precise regulation of protein expression profiles in mammalian cells by modulating target protein half-lives in a predictable manner. Using the well-established tetracycline gene-regulation system as a model, we show that the dynamics of protein expression can be tuned by fusing appropriate degron tags to gene regulators. Next, we apply this degron library to tune a synthetic pulse-generating circuit in mammalian cells. With this toolbox we establish a set of pulse generators with tailored pulse lengths and magnitudes of protein expression. This methodology will prove useful in the functional roles of essential proteins, fine-tuning of gene-expression systems, and enabling a higher complexity in the design of synthetic biological systems in mammalian cells.","lang":"eng"}],"oa_version":"Published Version","scopus_import":"1","month":"05","intvolume":" 10","date_updated":"2023-08-25T10:33:51Z","ddc":["570"],"department":[{"_id":"CaGu"}],"file_date_updated":"2020-07-14T12:47:31Z","_id":"6465","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","has_accepted_license":"1","isi":1,"year":"2019","day":"01","publication":"Nature Communications","doi":"10.1038/s41467-019-09974-5","date_published":"2019-05-01T00:00:00Z","date_created":"2019-05-19T21:59:14Z","quality_controlled":"1","publisher":"Springer Nature","oa":1,"citation":{"apa":"Chassin, H., Müller, M., Tigges, M., Scheller, L., Lang, M., & Fussenegger, M. (2019). A modular degron library for synthetic circuits in mammalian cells. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-019-09974-5","ama":"Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. A modular degron library for synthetic circuits in mammalian cells. Nature Communications. 2019;10(1). doi:10.1038/s41467-019-09974-5","short":"H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, M. Fussenegger, Nature Communications 10 (2019).","ieee":"H. Chassin, M. Müller, M. Tigges, L. Scheller, M. Lang, and M. Fussenegger, “A modular degron library for synthetic circuits in mammalian cells,” Nature Communications, vol. 10, no. 1. Springer Nature, 2019.","mla":"Chassin, Hélène, et al. “A Modular Degron Library for Synthetic Circuits in Mammalian Cells.” Nature Communications, vol. 10, no. 1, 2013, Springer Nature, 2019, doi:10.1038/s41467-019-09974-5.","ista":"Chassin H, Müller M, Tigges M, Scheller L, Lang M, Fussenegger M. 2019. A modular degron library for synthetic circuits in mammalian cells. Nature Communications. 10(1), 2013.","chicago":"Chassin, Hélène, Marius Müller, Marcel Tigges, Leo Scheller, Moritz Lang, and Martin Fussenegger. “A Modular Degron Library for Synthetic Circuits in Mammalian Cells.” Nature Communications. Springer Nature, 2019. https://doi.org/10.1038/s41467-019-09974-5."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"first_name":"Hélène","last_name":"Chassin","full_name":"Chassin, Hélène"},{"first_name":"Marius","full_name":"Müller, Marius","last_name":"Müller"},{"first_name":"Marcel","last_name":"Tigges","full_name":"Tigges, Marcel"},{"first_name":"Leo","last_name":"Scheller","full_name":"Scheller, Leo"},{"full_name":"Lang, Moritz","last_name":"Lang","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","first_name":"Moritz"},{"first_name":"Martin","last_name":"Fussenegger","full_name":"Fussenegger, Martin"}],"article_processing_charge":"No","external_id":{"isi":["000466338600006"]},"title":"A modular degron library for synthetic circuits in mammalian cells","article_number":"2013"},{"scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1073/pnas.1812015116"}],"month":"02","intvolume":" 116","abstract":[{"text":"The abelian sandpile serves as a model to study self-organized criticality, a phenomenon occurring in biological, physical and social processes. The identity of the abelian group is a fractal composed of self-similar patches, and its limit is subject of extensive collaborative research. Here, we analyze the evolution of the sandpile identity under harmonic fields of different orders. We show that this evolution corresponds to periodic cycles through the abelian group characterized by the smooth transformation and apparent conservation of the patches constituting the identity. The dynamics induced by second and third order harmonics resemble smooth stretchings, respectively translations, of the identity, while the ones induced by fourth order harmonics resemble magnifications and rotations. Starting with order three, the dynamics pass through extended regions of seemingly random configurations which spontaneously reassemble into accentuated patterns. We show that the space of harmonic functions projects to the extended analogue of the sandpile group, thus providing a set of universal coordinates identifying configurations between different domains. Since the original sandpile group is a subgroup of the extended one, this directly implies that it admits a natural renormalization. Furthermore, we show that the harmonic fields can be induced by simple Markov processes, and that the corresponding stochastic dynamics show remarkable robustness over hundreds of periods. Finally, we encode information into seemingly random configurations, and decode this information with an algorithm requiring minimal prior knowledge. Our results suggest that harmonic fields might split the sandpile group into sub-sets showing different critical coefficients, and that it might be possible to extend the fractal structure of the identity beyond the boundaries of its domain. ","lang":"eng"}],"oa_version":"Published Version","pmid":1,"related_material":{"link":[{"description":"News on IST Webpage","relation":"press_release","url":"https://ist.ac.at/en/news/famous-sandpile-model-shown-to-move-like-a-traveling-sand-dune/"}]},"issue":"8","volume":116,"publication_identifier":{"eissn":["1091-6490"]},"publication_status":"published","language":[{"iso":"eng"}],"article_type":"original","type":"journal_article","status":"public","_id":"196","department":[{"_id":"CaGu"},{"_id":"GaTk"},{"_id":"TaHa"}],"date_updated":"2023-09-11T14:09:34Z","quality_controlled":"1","publisher":"National Academy of Sciences","oa":1,"acknowledgement":"M.L. is grateful to the members of the C Guet and G Tkacik groups for valuable comments and support. M.S. is grateful to Nikita Kalinin for inspiring communications.\r\n","page":"2821-2830","date_published":"2019-02-19T00:00:00Z","doi":"10.1073/pnas.1812015116","date_created":"2018-12-11T11:45:08Z","isi":1,"year":"2019","day":"19","publication":"Proceedings of the National Academy of Sciences","author":[{"first_name":"Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","full_name":"Lang, Moritz","last_name":"Lang"},{"first_name":"Mikhail","id":"35084A62-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4310-178X","full_name":"Shkolnikov, Mikhail","last_name":"Shkolnikov"}],"external_id":{"arxiv":["1806.10823"],"pmid":[" 30728300"],"isi":["000459074400013"]},"article_processing_charge":"No","title":"Harmonic dynamics of the Abelian sandpile","citation":{"mla":"Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.” Proceedings of the National Academy of Sciences, vol. 116, no. 8, National Academy of Sciences, 2019, pp. 2821–30, doi:10.1073/pnas.1812015116.","apa":"Lang, M., & Shkolnikov, M. (2019). Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences. National Academy of Sciences. https://doi.org/10.1073/pnas.1812015116","ama":"Lang M, Shkolnikov M. Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences. 2019;116(8):2821-2830. doi:10.1073/pnas.1812015116","short":"M. Lang, M. Shkolnikov, Proceedings of the National Academy of Sciences 116 (2019) 2821–2830.","ieee":"M. Lang and M. Shkolnikov, “Harmonic dynamics of the Abelian sandpile,” Proceedings of the National Academy of Sciences, vol. 116, no. 8. National Academy of Sciences, pp. 2821–2830, 2019.","chicago":"Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.” Proceedings of the National Academy of Sciences. National Academy of Sciences, 2019. https://doi.org/10.1073/pnas.1812015116.","ista":"Lang M, Shkolnikov M. 2019. Harmonic dynamics of the Abelian sandpile. Proceedings of the National Academy of Sciences. 116(8), 2821–2830."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1"},{"type":"journal_article","status":"public","_id":"305","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"date_updated":"2021-01-12T07:40:42Z","scopus_import":1,"alternative_title":["MIMB"],"month":"01","intvolume":" 1771","abstract":[{"lang":"eng","text":"The hanging-drop network (HDN) is a technology platform based on a completely open microfluidic network at the bottom of an inverted, surface-patterned substrate. The platform is predominantly used for the formation, culturing, and interaction of self-assembled spherical microtissues (spheroids) under precisely controlled flow conditions. Here, we describe design, fabrication, and operation of microfluidic hanging-drop networks."}],"oa_version":"None","volume":1771,"ec_funded":1,"publication_status":"published","language":[{"iso":"eng"}],"project":[{"name":"International IST Postdoc Fellowship Programme","grant_number":"291734","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425"}],"author":[{"full_name":"Misun, Patrick","last_name":"Misun","first_name":"Patrick"},{"full_name":"Birchler, Axel","last_name":"Birchler","first_name":"Axel"},{"first_name":"Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","last_name":"Lang","full_name":"Lang, Moritz"},{"first_name":"Andreas","last_name":"Hierlemann","full_name":"Hierlemann, Andreas"},{"full_name":"Frey, Olivier","last_name":"Frey","first_name":"Olivier"}],"publist_id":"7574","title":"Fabrication and operation of microfluidic hanging drop networks","citation":{"chicago":"Misun, Patrick, Axel Birchler, Moritz Lang, Andreas Hierlemann, and Olivier Frey. “Fabrication and Operation of Microfluidic Hanging Drop Networks.” Methods in Molecular Biology. Springer, 2018. https://doi.org/10.1007/978-1-4939-7792-5_15.","ista":"Misun P, Birchler A, Lang M, Hierlemann A, Frey O. 2018. Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. 1771, 183–202.","mla":"Misun, Patrick, et al. “Fabrication and Operation of Microfluidic Hanging Drop Networks.” Methods in Molecular Biology, vol. 1771, Springer, 2018, pp. 183–202, doi:10.1007/978-1-4939-7792-5_15.","ama":"Misun P, Birchler A, Lang M, Hierlemann A, Frey O. Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. 2018;1771:183-202. doi:10.1007/978-1-4939-7792-5_15","apa":"Misun, P., Birchler, A., Lang, M., Hierlemann, A., & Frey, O. (2018). Fabrication and operation of microfluidic hanging drop networks. Methods in Molecular Biology. Springer. https://doi.org/10.1007/978-1-4939-7792-5_15","short":"P. Misun, A. Birchler, M. Lang, A. Hierlemann, O. Frey, Methods in Molecular Biology 1771 (2018) 183–202.","ieee":"P. Misun, A. Birchler, M. Lang, A. Hierlemann, and O. Frey, “Fabrication and operation of microfluidic hanging drop networks,” Methods in Molecular Biology, vol. 1771. Springer, pp. 183–202, 2018."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","publisher":"Springer","acknowledgement":"This work was financially supported by FP7 of the EU through the project “Body on a chip,” ICT-FET-296257, and the ERC Advanced Grant “NeuroCMOS” (contract 267351), as well as by an individual Ambizione Grant 142440 from the Swiss National Science Foundation for Olivier Frey. The research leading to these results also received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. [291734]. We would like to thank Alexander Stettler, ETH Zurich for his expertise and support in the cleanroom, and we acknowledge the Single Cell Unit of D-BSSE, ETH Zurich for assistance in microscopy issues. M.L. is grateful to the members of the Guet and Tkačik groups, IST Austria, for valuable comments and support.","page":"183 - 202","doi":"10.1007/978-1-4939-7792-5_15","date_published":"2018-01-01T00:00:00Z","date_created":"2018-12-11T11:45:43Z","year":"2018","day":"01","publication":"Methods in Molecular Biology"},{"_id":"457","status":"public","type":"journal_article","date_updated":"2023-09-15T12:04:57Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"oa_version":"None","abstract":[{"text":"Temperate bacteriophages integrate in bacterial genomes as prophages and represent an important source of genetic variation for bacterial evolution, frequently transmitting fitness-augmenting genes such as toxins responsible for virulence of major pathogens. However, only a fraction of bacteriophage infections are lysogenic and lead to prophage acquisition, whereas the majority are lytic and kill the infected bacteria. Unless able to discriminate lytic from lysogenic infections, mechanisms of immunity to bacteriophages are expected to act as a double-edged sword and increase the odds of survival at the cost of depriving bacteria of potentially beneficial prophages. We show that although restriction-modification systems as mechanisms of innate immunity prevent both lytic and lysogenic infections indiscriminately in individual bacteria, they increase the number of prophage-acquiring individuals at the population level. We find that this counterintuitive result is a consequence of phage-host population dynamics, in which restriction-modification systems delay infection onset until bacteria reach densities at which the probability of lysogeny increases. These results underscore the importance of population-level dynamics as a key factor modulating costs and benefits of immunity to temperate bacteriophages","lang":"eng"}],"intvolume":" 2","month":"02","scopus_import":"1","language":[{"iso":"eng"}],"publication_status":"published","ec_funded":1,"volume":2,"issue":"2","related_material":{"record":[{"id":"202","status":"public","relation":"dissertation_contains"}]},"project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"},{"grant_number":"RGY0079/2011","name":"Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification Systems (HFSP Young investigators' grant)","_id":"251BCBEC-B435-11E9-9278-68D0E5697425"},{"_id":"251D65D8-B435-11E9-9278-68D0E5697425","grant_number":"24210","name":"Effects of Stochasticity on the Function of Restriction-Modi cation Systems at the Single-Cell Level (DOC Fellowship)"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ista":"Pleska M, Lang M, Refardt D, Levin B, Guet CC. 2018. Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. Nature Ecology and Evolution. 2(2), 359–366.","chicago":"Pleska, Maros, Moritz Lang, Dominik Refardt, Bruce Levin, and Calin C Guet. “Phage-Host Population Dynamics Promotes Prophage Acquisition in Bacteria with Innate Immunity.” Nature Ecology and Evolution. Springer Nature, 2018. https://doi.org/10.1038/s41559-017-0424-z.","short":"M. Pleska, M. Lang, D. Refardt, B. Levin, C.C. Guet, Nature Ecology and Evolution 2 (2018) 359–366.","ieee":"M. Pleska, M. Lang, D. Refardt, B. Levin, and C. C. Guet, “Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity,” Nature Ecology and Evolution, vol. 2, no. 2. Springer Nature, pp. 359–366, 2018.","apa":"Pleska, M., Lang, M., Refardt, D., Levin, B., & Guet, C. C. (2018). Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. Nature Ecology and Evolution. Springer Nature. https://doi.org/10.1038/s41559-017-0424-z","ama":"Pleska M, Lang M, Refardt D, Levin B, Guet CC. Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity. Nature Ecology and Evolution. 2018;2(2):359-366. doi:10.1038/s41559-017-0424-z","mla":"Pleska, Maros, et al. “Phage-Host Population Dynamics Promotes Prophage Acquisition in Bacteria with Innate Immunity.” Nature Ecology and Evolution, vol. 2, no. 2, Springer Nature, 2018, pp. 359–66, doi:10.1038/s41559-017-0424-z."},"title":"Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity","article_processing_charge":"No","external_id":{"isi":["000426516400027"]},"publist_id":"7364","author":[{"id":"4569785E-F248-11E8-B48F-1D18A9856A87","first_name":"Maros","last_name":"Pleska","orcid":"0000-0001-7460-7479","full_name":"Pleska, Maros"},{"last_name":"Lang","full_name":"Lang, Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","first_name":"Moritz"},{"last_name":"Refardt","full_name":"Refardt, Dominik","first_name":"Dominik"},{"full_name":"Levin, Bruce","last_name":"Levin","first_name":"Bruce"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","first_name":"Calin C","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052","last_name":"Guet"}],"quality_controlled":"1","publisher":"Springer Nature","publication":"Nature Ecology and Evolution","day":"01","year":"2018","isi":1,"date_created":"2018-12-11T11:46:35Z","doi":"10.1038/s41559-017-0424-z","date_published":"2018-02-01T00:00:00Z","page":"359 - 366"},{"date_created":"2018-12-11T11:49:39Z","date_published":"2017-06-01T00:00:00Z","doi":"10.1016/j.automatica.2017.03.030","page":"46 - 55","publication":"Automatica","day":"01","year":"2017","has_accepted_license":"1","isi":1,"oa":1,"quality_controlled":"1","publisher":"International Federation of Automatic Control","title":"Zeros of nonlinear systems with input invariances","external_id":{"isi":["000403513900006"]},"article_processing_charge":"Yes (in subscription journal)","publist_id":"6391","author":[{"id":"29E0800A-F248-11E8-B48F-1D18A9856A87","first_name":"Moritz","full_name":"Lang, Moritz","last_name":"Lang"},{"last_name":"Sontag","full_name":"Sontag, Eduardo","first_name":"Eduardo"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"short":"M. Lang, E. Sontag, Automatica 81C (2017) 46–55.","ieee":"M. Lang and E. Sontag, “Zeros of nonlinear systems with input invariances,” Automatica, vol. 81C. International Federation of Automatic Control, pp. 46–55, 2017.","apa":"Lang, M., & Sontag, E. (2017). Zeros of nonlinear systems with input invariances. Automatica. International Federation of Automatic Control. https://doi.org/10.1016/j.automatica.2017.03.030","ama":"Lang M, Sontag E. Zeros of nonlinear systems with input invariances. Automatica. 2017;81C:46-55. doi:10.1016/j.automatica.2017.03.030","mla":"Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” Automatica, vol. 81C, International Federation of Automatic Control, 2017, pp. 46–55, doi:10.1016/j.automatica.2017.03.030.","ista":"Lang M, Sontag E. 2017. Zeros of nonlinear systems with input invariances. Automatica. 81C, 46–55.","chicago":"Lang, Moritz, and Eduardo Sontag. “Zeros of Nonlinear Systems with Input Invariances.” Automatica. International Federation of Automatic Control, 2017. https://doi.org/10.1016/j.automatica.2017.03.030."},"project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","grant_number":"291734"}],"ec_funded":1,"volume":"81C","language":[{"iso":"eng"}],"file":[{"file_size":1401954,"date_updated":"2018-12-12T10:11:29Z","creator":"system","file_name":"IST-2017-813-v1+1_ZerosOfNonlinearSystems.pdf","date_created":"2018-12-12T10:11:29Z","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_id":"4884"}],"publication_status":"published","publication_identifier":{"issn":["0005-1098"]},"month":"06","scopus_import":"1","oa_version":"Published Version","abstract":[{"text":"A nonlinear system possesses an invariance with respect to a set of transformations if its output dynamics remain invariant when transforming the input, and adjusting the initial condition accordingly. Most research has focused on invariances with respect to time-independent pointwise transformations like translational-invariance (u(t) -> u(t) + p, p in R) or scale-invariance (u(t) -> pu(t), p in R>0). In this article, we introduce the concept of s0-invariances with respect to continuous input transformations exponentially growing/decaying over time. We show that s0-invariant systems not only encompass linear time-invariant (LTI) systems with transfer functions having an irreducible zero at s0 in R, but also that the input/output relationship of nonlinear s0-invariant systems possesses properties well known from their linear counterparts. Furthermore, we extend the concept of s0-invariances to second- and higher-order s0-invariances, corresponding to invariances with respect to transformations of the time-derivatives of the input, and encompassing LTI systems with zeros of multiplicity two or higher. Finally, we show that nth-order 0-invariant systems realize – under mild conditions – nth-order nonlinear differential operators: when excited by an input of a characteristic functional form, the system’s output converges to a constant value only depending on the nth (nonlinear) derivative of the input.","lang":"eng"}],"file_date_updated":"2018-12-12T10:11:29Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"ddc":["000"],"date_updated":"2023-10-17T08:51:18Z","pubrep_id":"813","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","_id":"1007"},{"quality_controlled":"1","publisher":"Cell Press","date_created":"2018-12-11T11:48:13Z","date_published":"2017-10-23T00:00:00Z","doi":"10.1016/j.devcel.2017.09.014","page":"198 - 211","publication":"Developmental Cell","day":"23","year":"2017","isi":1,"project":[{"_id":"25681D80-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"International IST Postdoc Fellowship Programme","grant_number":"291734"},{"grant_number":"I2058","name":"Cell segregation in gastrulation: the role of cell fate specification","call_identifier":"FWF","_id":"252DD2A6-B435-11E9-9278-68D0E5697425"}],"title":"An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate","external_id":{"isi":["000413443700011"]},"article_processing_charge":"No","publist_id":"6934","author":[{"id":"419EECCC-F248-11E8-B48F-1D18A9856A87","first_name":"Vanessa","last_name":"Barone","orcid":"0000-0003-2676-3367","full_name":"Barone, Vanessa"},{"id":"29E0800A-F248-11E8-B48F-1D18A9856A87","first_name":"Moritz","full_name":"Lang, Moritz","last_name":"Lang"},{"first_name":"Gabriel","id":"2B819732-F248-11E8-B48F-1D18A9856A87","last_name":"Krens","orcid":"0000-0003-4761-5996","full_name":"Krens, Gabriel"},{"first_name":"Saurabh","full_name":"Pradhan, Saurabh","last_name":"Pradhan"},{"first_name":"Shayan","id":"40B34FE2-F248-11E8-B48F-1D18A9856A87","last_name":"Shamipour","full_name":"Shamipour, Shayan"},{"orcid":"0000-0002-6453-8075","full_name":"Sako, Keisuke","last_name":"Sako","first_name":"Keisuke","id":"3BED66BE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Mateusz K","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","full_name":"Sikora, Mateusz K","last_name":"Sikora"},{"first_name":"Calin C","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","last_name":"Guet","full_name":"Guet, Calin C","orcid":"0000-0001-6220-2052"},{"orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J","last_name":"Heisenberg","id":"39427864-F248-11E8-B48F-1D18A9856A87","first_name":"Carl-Philipp J"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Barone, Vanessa, Moritz Lang, Gabriel Krens, Saurabh Pradhan, Shayan Shamipour, Keisuke Sako, Mateusz K Sikora, Calin C Guet, and Carl-Philipp J Heisenberg. “An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate.” Developmental Cell. Cell Press, 2017. https://doi.org/10.1016/j.devcel.2017.09.014.","ista":"Barone V, Lang M, Krens G, Pradhan S, Shamipour S, Sako K, Sikora MK, Guet CC, Heisenberg C-PJ. 2017. An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. 43(2), 198–211.","mla":"Barone, Vanessa, et al. “An Effective Feedback Loop between Cell-Cell Contact Duration and Morphogen Signaling Determines Cell Fate.” Developmental Cell, vol. 43, no. 2, Cell Press, 2017, pp. 198–211, doi:10.1016/j.devcel.2017.09.014.","apa":"Barone, V., Lang, M., Krens, G., Pradhan, S., Shamipour, S., Sako, K., … Heisenberg, C.-P. J. (2017). An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. Cell Press. https://doi.org/10.1016/j.devcel.2017.09.014","ama":"Barone V, Lang M, Krens G, et al. An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate. Developmental Cell. 2017;43(2):198-211. doi:10.1016/j.devcel.2017.09.014","ieee":"V. Barone et al., “An effective feedback loop between cell-cell contact duration and morphogen signaling determines cell fate,” Developmental Cell, vol. 43, no. 2. Cell Press, pp. 198–211, 2017.","short":"V. Barone, M. Lang, G. Krens, S. Pradhan, S. Shamipour, K. Sako, M.K. Sikora, C.C. Guet, C.-P.J. Heisenberg, Developmental Cell 43 (2017) 198–211."},"intvolume":" 43","month":"10","scopus_import":"1","oa_version":"None","abstract":[{"lang":"eng","text":"Cell-cell contact formation constitutes an essential step in evolution, leading to the differentiation of specialized cell types. However, remarkably little is known about whether and how the interplay between contact formation and fate specification affects development. Here, we identify a positive feedback loop between cell-cell contact duration, morphogen signaling, and mesendoderm cell-fate specification during zebrafish gastrulation. We show that long-lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for ppl cell-fate specification. We further show that Nodal signaling promotes ppl cell-cell contact duration, generating a positive feedback loop between ppl cell-cell contact duration and cell-fate specification. Finally, by combining mathematical modeling and experimentation, we show that this feedback determines whether anterior axial mesendoderm cells become ppl or, instead, turn into endoderm. Thus, the interdependent activities of cell-cell signaling and contact formation control fate diversification within the developing embryo."}],"ec_funded":1,"related_material":{"record":[{"relation":"dissertation_contains","id":"961","status":"public"},{"status":"public","id":"8350","relation":"dissertation_contains"}]},"issue":"2","volume":43,"language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"issn":["15345807"]},"status":"public","type":"journal_article","_id":"735","department":[{"_id":"CaHe"},{"_id":"CaGu"},{"_id":"GaTk"}],"date_updated":"2024-03-27T23:30:38Z"},{"_id":"1008","type":"journal_article","status":"public","date_updated":"2021-01-12T06:47:37Z","citation":{"chicago":"Gnügge, Robert, Lekshmi Dharmarajan, Moritz Lang, and Jörg Stelling. “An Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” ACS Synthetic Biology. American Chemical Society, 2016. https://doi.org/10.1021/acssynbio.6b00013.","ista":"Gnügge R, Dharmarajan L, Lang M, Stelling J. 2016. An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. 5(10), 1098–1107.","mla":"Gnügge, Robert, et al. “An Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” ACS Synthetic Biology, vol. 5, no. 10, American Chemical Society, 2016, pp. 1098–107, doi:10.1021/acssynbio.6b00013.","ama":"Gnügge R, Dharmarajan L, Lang M, Stelling J. An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. 2016;5(10):1098-1107. doi:10.1021/acssynbio.6b00013","apa":"Gnügge, R., Dharmarajan, L., Lang, M., & Stelling, J. (2016). An orthogonal permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology. American Chemical Society. https://doi.org/10.1021/acssynbio.6b00013","ieee":"R. Gnügge, L. Dharmarajan, M. Lang, and J. Stelling, “An orthogonal permease–inducer–repressor feedback loop shows bistability,” ACS Synthetic Biology, vol. 5, no. 10. American Chemical Society, pp. 1098–1107, 2016.","short":"R. Gnügge, L. Dharmarajan, M. Lang, J. Stelling, ACS Synthetic Biology 5 (2016) 1098–1107."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","publist_id":"6390","author":[{"first_name":"Robert","full_name":"Gnügge, Robert","last_name":"Gnügge"},{"full_name":"Dharmarajan, Lekshmi","last_name":"Dharmarajan","first_name":"Lekshmi"},{"last_name":"Lang","full_name":"Lang, Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","first_name":"Moritz"},{"first_name":"Jörg","full_name":"Stelling, Jörg","last_name":"Stelling"}],"department":[{"_id":"CaGu"}],"title":"An orthogonal permease–inducer–repressor feedback loop shows bistability","abstract":[{"lang":"eng","text":"Feedback loops in biological networks, among others, enable differentiation and cell cycle progression, and increase robustness in signal transduction. In natural networks, feedback loops are often complex and intertwined, making it challenging to identify which loops are mainly responsible for an observed behavior. However, minimal synthetic replicas could allow for such identification. Here, we engineered a synthetic permease-inducer-repressor system in Saccharomyces cerevisiae to analyze if a transport-mediated positive feedback loop could be a core mechanism for the switch-like behavior in the regulation of metabolic gene networks such as the S. cerevisiae GAL system or the Escherichia coli lac operon. We characterized the synthetic circuit using deterministic and stochastic mathematical models. Similar to its natural counterparts, our synthetic system shows bistable and hysteretic behavior, and the inducer concentration range for bistability as well as the switching rates between the two stable states depend on the repressor concentration. Our results indicate that a generic permease–inducer–repressor circuit with a single feedback loop is sufficient to explain the experimentally observed bistable behavior of the natural systems. We anticipate that the approach of reimplementing natural systems with orthogonal parts to identify crucial network components is applicable to other natural systems such as signaling pathways."}],"acknowledgement":"We thank Julio Polaina (Instituto de Agroqu ı ́ mica y Tecnolog ı ́ a de Alimentos, C.S.I.C., Paterna, Spain) for the gift of plasmid pMR4, Gregor W. Schmidt for provision of and support with the micro fl uidic device, Markus Du ̈ rr for the cell tracking R script, and Lukas Widmer for the script for MEIGO using “ parfor ” in MATLAB. We acknowledge the members of the Stelling group for discussions, comments, and support.","oa_version":"None","quality_controlled":"1","publisher":"American Chemical Society","intvolume":" 5","month":"05","year":"2016","publication_status":"published","publication":"ACS Synthetic Biology","language":[{"iso":"eng"}],"day":"05","page":"1098 - 1107","date_created":"2018-12-11T11:49:40Z","date_published":"2016-05-05T00:00:00Z","doi":"10.1021/acssynbio.6b00013","volume":5,"issue":"10"},{"department":[{"_id":"CaGu"},{"_id":"GaTk"}],"file_date_updated":"2020-07-14T12:44:37Z","date_updated":"2021-01-12T06:48:49Z","ddc":["003","518","570","621"],"type":"journal_article","status":"public","pubrep_id":"811","_id":"1170","issue":"6","volume":38,"publication_status":"published","file":[{"checksum":"781bc3ffd30b2dd65b7727c5a285fc78","file_id":"5095","relation":"main_file","access_level":"local","content_type":"application/pdf","file_name":"IST-2017-811-v1+1_modular_parameter_identification.pdf","date_created":"2018-12-12T10:14:41Z","creator":"system","file_size":871964,"date_updated":"2020-07-14T12:44:37Z"}],"language":[{"iso":"eng"}],"scopus_import":1,"month":"11","intvolume":" 38","abstract":[{"text":"The increasing complexity of dynamic models in systems and synthetic biology poses computational challenges especially for the identification of model parameters. While modularization of the corresponding optimization problems could help reduce the “curse of dimensionality,” abundant feedback and crosstalk mechanisms prohibit a simple decomposition of most biomolecular networks into subnetworks, or modules. Drawing on ideas from network modularization and multiple-shooting optimization, we present here a modular parameter identification approach that explicitly allows for such interdependencies. Interfaces between our modules are given by the experimentally measured molecular species. This definition allows deriving good (initial) estimates for the inter-module communication directly from the experimental data. Given these estimates, the states and parameter sensitivities of different modules can be integrated independently. To achieve consistency between modules, we iteratively adjust the estimates for inter-module communication while optimizing the parameters. After convergence to an optimal parameter set---but not during earlier iterations---the intermodule communication as well as the individual modules\\' state dynamics agree with the dynamics of the nonmodularized network. Our modular parameter identification approach allows for easy parallelization; it can reduce the computational complexity for larger networks and decrease the probability to converge to suboptimal local minima. We demonstrate the algorithm\\'s performance in parameter estimation for two biomolecular networks, a synthetic genetic oscillator and a mammalian signaling pathway.","lang":"eng"}],"oa_version":"Submitted Version","author":[{"first_name":"Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","last_name":"Lang","full_name":"Lang, Moritz"},{"first_name":"Jörg","full_name":"Stelling, Jörg","last_name":"Stelling"}],"publist_id":"6186","title":"Modular parameter identification of biomolecular networks","citation":{"chicago":"Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular Networks.” SIAM Journal on Scientific Computing. Society for Industrial and Applied Mathematics , 2016. https://doi.org/10.1137/15M103306X.","ista":"Lang M, Stelling J. 2016. Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. 38(6), B988–B1008.","mla":"Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular Networks.” SIAM Journal on Scientific Computing, vol. 38, no. 6, Society for Industrial and Applied Mathematics , 2016, pp. B988–1008, doi:10.1137/15M103306X.","ieee":"M. Lang and J. Stelling, “Modular parameter identification of biomolecular networks,” SIAM Journal on Scientific Computing, vol. 38, no. 6. Society for Industrial and Applied Mathematics , pp. B988–B1008, 2016.","short":"M. Lang, J. Stelling, SIAM Journal on Scientific Computing 38 (2016) B988–B1008.","apa":"Lang, M., & Stelling, J. (2016). Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. Society for Industrial and Applied Mathematics . https://doi.org/10.1137/15M103306X","ama":"Lang M, Stelling J. Modular parameter identification of biomolecular networks. SIAM Journal on Scientific Computing. 2016;38(6):B988-B1008. doi:10.1137/15M103306X"},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","page":"B988 - B1008","doi":"10.1137/15M103306X","date_published":"2016-11-15T00:00:00Z","date_created":"2018-12-11T11:50:31Z","has_accepted_license":"1","year":"2016","day":"15","publication":"SIAM Journal on Scientific Computing","publisher":"Society for Industrial and Applied Mathematics ","quality_controlled":"1"},{"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Lang M, Sontag E. 2016. Scale-invariant systems realize nonlinear differential operators. ACC: American Control Conference vol. 2016–July, 7526722.","chicago":"Lang, Moritz, and Eduardo Sontag. “Scale-Invariant Systems Realize Nonlinear Differential Operators,” Vol. 2016–July. IEEE, 2016. https://doi.org/10.1109/ACC.2016.7526722.","apa":"Lang, M., & Sontag, E. (2016). Scale-invariant systems realize nonlinear differential operators (Vol. 2016–July). Presented at the ACC: American Control Conference, Boston, MA, USA: IEEE. https://doi.org/10.1109/ACC.2016.7526722","ama":"Lang M, Sontag E. Scale-invariant systems realize nonlinear differential operators. In: Vol 2016-July. IEEE; 2016. doi:10.1109/ACC.2016.7526722","ieee":"M. Lang and E. Sontag, “Scale-invariant systems realize nonlinear differential operators,” presented at the ACC: American Control Conference, Boston, MA, USA, 2016, vol. 2016–July.","short":"M. Lang, E. Sontag, in:, IEEE, 2016.","mla":"Lang, Moritz, and Eduardo Sontag. Scale-Invariant Systems Realize Nonlinear Differential Operators. Vol. 2016–July, 7526722, IEEE, 2016, doi:10.1109/ACC.2016.7526722."},"title":"Scale-invariant systems realize nonlinear differential operators","publist_id":"5950","author":[{"first_name":"Moritz","id":"29E0800A-F248-11E8-B48F-1D18A9856A87","last_name":"Lang","full_name":"Lang, Moritz"},{"last_name":"Sontag","full_name":"Sontag, Eduardo","first_name":"Eduardo"}],"article_number":"7526722","project":[{"call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","grant_number":"291734","name":"International IST Postdoc Fellowship Programme"}],"day":"28","year":"2016","has_accepted_license":"1","date_created":"2018-12-11T11:51:21Z","date_published":"2016-07-28T00:00:00Z","doi":"10.1109/ACC.2016.7526722","acknowledgement":"The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement n° [291734]. Work supported in part by grants AFOSR FA9550-14-1-0060 and NIH 1R01GM100473.","quality_controlled":"1","publisher":"IEEE","ddc":["003","621"],"date_updated":"2021-01-12T06:49:51Z","file_date_updated":"2020-07-14T12:44:43Z","department":[{"_id":"CaGu"},{"_id":"GaTk"}],"_id":"1320","pubrep_id":"810","status":"public","conference":{"name":"ACC: American Control Conference","start_date":"2016-07-06","location":"Boston, MA, USA","end_date":"2016-07-08"},"type":"conference","language":[{"iso":"eng"}],"file":[{"checksum":"7219432b43defc62a0d45f48d4ce6a19","file_id":"5203","content_type":"application/pdf","access_level":"local","relation":"main_file","date_created":"2018-12-12T10:16:17Z","file_name":"IST-2017-810-v1+1_root.pdf","date_updated":"2020-07-14T12:44:43Z","file_size":539166,"creator":"system"}],"publication_status":"published","ec_funded":1,"volume":"2016-July","oa_version":"Preprint","abstract":[{"lang":"eng","text":"In recent years, several biomolecular systems have been shown to be scale-invariant (SI), i.e. to show the same output dynamics when exposed to geometrically scaled input signals (u → pu, p > 0) after pre-adaptation to accordingly scaled constant inputs. In this article, we show that SI systems-as well as systems invariant with respect to other input transformations-can realize nonlinear differential operators: when excited by inputs obeying functional forms characteristic for a given class of invariant systems, the systems' outputs converge to constant values directly quantifying the speed of the input."}],"month":"07","scopus_import":1}]