[{"publication_status":"published","publisher":"Elsevier","department":[{"_id":"ToHe"},{"_id":"CaGu"}],"year":"2021","acknowledgement":"Tatjana Petrov’s research was supported in part by SNSF Advanced Postdoctoral Mobility Fellowship grant number P300P2 161067, the Ministry of Science, Research and the Arts of the state of Baden-Wurttemberg, and the DFG Centre of Excellence 2117 ‘Centre for the Advanced Study of Collective Behaviour’ (ID: 422037984). Claudia Igler is the recipient of a DOC Fellowship of the Austrian Academy of Sciences. Thomas A. Henzinger’s research was supported in part by the Austrian Science Fund (FWF) under grant Z211-N23 (Wittgenstein Award).","date_updated":"2023-08-10T14:11:19Z","date_created":"2021-07-11T22:01:18Z","volume":893,"author":[{"first_name":"Tatjana","last_name":"Petrov","full_name":"Petrov, Tatjana"},{"first_name":"Claudia","last_name":"Igler","id":"46613666-F248-11E8-B48F-1D18A9856A87","full_name":"Igler, Claudia"},{"full_name":"Sezgin, Ali","id":"4C7638DA-F248-11E8-B48F-1D18A9856A87","first_name":"Ali","last_name":"Sezgin"},{"full_name":"Henzinger, Thomas A","last_name":"Henzinger","first_name":"Thomas A","orcid":"0000-0002-2985-7724","id":"40876CD8-F248-11E8-B48F-1D18A9856A87"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C"}],"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","file_date_updated":"2022-05-12T12:13:27Z","quality_controlled":"1","isi":1,"project":[{"name":"The Wittgenstein Prize","call_identifier":"FWF","grant_number":"Z211","_id":"25F42A32-B435-11E9-9278-68D0E5697425"}],"external_id":{"isi":["000710180500002"]},"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1016/j.tcs.2021.05.023","month":"06","publication_identifier":{"issn":["0304-3975"]},"title":"Long lived transients in gene regulation","status":"public","ddc":["004"],"intvolume":" 893","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"9647","oa_version":"Published Version","file":[{"relation":"main_file","file_id":"11364","date_created":"2022-05-12T12:13:27Z","date_updated":"2022-05-12T12:13:27Z","checksum":"d3aef34cfb13e53bba4cf44d01680793","success":1,"file_name":"2021_TheoreticalComputerScience_Petrov.pdf","access_level":"open_access","content_type":"application/pdf","file_size":2566504,"creator":"dernst"}],"type":"journal_article","abstract":[{"lang":"eng","text":"Gene expression is regulated by the set of transcription factors (TFs) that bind to the promoter. The ensuing regulating function is often represented as a combinational logic circuit, where output (gene expression) is determined by current input values (promoter bound TFs) only. However, the simultaneous arrival of TFs is a strong assumption, since transcription and translation of genes introduce intrinsic time delays and there is no global synchronisation among the arrival times of different molecular species at their targets. We present an experimentally implementable genetic circuit with two inputs and one output, which in the presence of small delays in input arrival, exhibits qualitatively distinct population-level phenotypes, over timescales that are longer than typical cell doubling times. From a dynamical systems point of view, these phenotypes represent long-lived transients: although they converge to the same value eventually, they do so after a very long time span. The key feature of this toy model genetic circuit is that, despite having only two inputs and one output, it is regulated by twenty-three distinct DNA-TF configurations, two of which are more stable than others (DNA looped states), one promoting and another blocking the expression of the output gene. Small delays in input arrival time result in a majority of cells in the population quickly reaching the stable state associated with the first input, while exiting of this stable state occurs at a slow timescale. In order to mechanistically model the behaviour of this genetic circuit, we used a rule-based modelling language, and implemented a grid-search to find parameter combinations giving rise to long-lived transients. Our analysis shows that in the absence of feedback, there exist path-dependent gene regulatory mechanisms based on the long timescale of transients. The behaviour of this toy model circuit suggests that gene regulatory networks can exploit event timing to create phenotypes, and it opens the possibility that they could use event timing to memorise events, without regulatory feedback. The model reveals the importance of (i) mechanistically modelling the transitions between the different DNA-TF states, and (ii) employing transient analysis thereof."}],"article_type":"original","page":"1-16","publication":"Theoretical Computer Science","citation":{"short":"T. Petrov, C. Igler, A. Sezgin, T.A. Henzinger, C.C. Guet, Theoretical Computer Science 893 (2021) 1–16.","mla":"Petrov, Tatjana, et al. “Long Lived Transients in Gene Regulation.” Theoretical Computer Science, vol. 893, Elsevier, 2021, pp. 1–16, doi:10.1016/j.tcs.2021.05.023.","chicago":"Petrov, Tatjana, Claudia Igler, Ali Sezgin, Thomas A Henzinger, and Calin C Guet. “Long Lived Transients in Gene Regulation.” Theoretical Computer Science. Elsevier, 2021. https://doi.org/10.1016/j.tcs.2021.05.023.","ama":"Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. Long lived transients in gene regulation. Theoretical Computer Science. 2021;893:1-16. doi:10.1016/j.tcs.2021.05.023","ieee":"T. Petrov, C. Igler, A. Sezgin, T. A. Henzinger, and C. C. Guet, “Long lived transients in gene regulation,” Theoretical Computer Science, vol. 893. Elsevier, pp. 1–16, 2021.","apa":"Petrov, T., Igler, C., Sezgin, A., Henzinger, T. A., & Guet, C. C. (2021). Long lived transients in gene regulation. Theoretical Computer Science. Elsevier. https://doi.org/10.1016/j.tcs.2021.05.023","ista":"Petrov T, Igler C, Sezgin A, Henzinger TA, Guet CC. 2021. Long lived transients in gene regulation. Theoretical Computer Science. 893, 1–16."},"date_published":"2021-06-04T00:00:00Z","scopus_import":"1","day":"04","has_accepted_license":"1","article_processing_charge":"No"},{"ec_funded":1,"file_date_updated":"2021-08-09T09:44:03Z","pmid":1,"year":"2021","acknowledgement":"We would like to thank Charlott Leu for the production of our chromium wafers, Louise Ritter for her contribution of the IF stainings in Figure 4, Shokoufeh Teymouri for her help with the Bioinert coated slides, and finally Prof. Dr. Joachim Rädler for his valuable scientific guidance.","publisher":"American Chemical Society","department":[{"_id":"MiSi"},{"_id":"GaTk"},{"_id":"Bio"},{"_id":"CaGu"}],"publication_status":"published","author":[{"full_name":"Zisis, Themistoklis","last_name":"Zisis","first_name":"Themistoklis"},{"id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","first_name":"Jan","last_name":"Schwarz","full_name":"Schwarz, Jan"},{"full_name":"Balles, Miriam","first_name":"Miriam","last_name":"Balles"},{"first_name":"Maibritt","last_name":"Kretschmer","full_name":"Kretschmer, Maibritt"},{"first_name":"Maria","last_name":"Nemethova","id":"34E27F1C-F248-11E8-B48F-1D18A9856A87","full_name":"Nemethova, Maria"},{"full_name":"Chait, Remy P","id":"3464AE84-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-0876-3187","first_name":"Remy P","last_name":"Chait"},{"full_name":"Hauschild, Robert","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","first_name":"Robert","last_name":"Hauschild"},{"full_name":"Lange, Janina","first_name":"Janina","last_name":"Lange"},{"id":"47F8433E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6220-2052","first_name":"Calin C","last_name":"Guet","full_name":"Guet, Calin C"},{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4561-241X","first_name":"Michael K","last_name":"Sixt"},{"full_name":"Zahler, Stefan","last_name":"Zahler","first_name":"Stefan"}],"volume":13,"date_updated":"2023-08-10T14:22:48Z","date_created":"2021-08-08T22:01:28Z","publication_identifier":{"issn":["19448244"],"eissn":["19448252"]},"month":"08","oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"external_id":{"pmid":["34283577"],"isi":["000683741400026"]},"project":[{"grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Cellular navigation along spatial gradients"}],"quality_controlled":"1","isi":1,"doi":"10.1021/acsami.1c09850","language":[{"iso":"eng"}],"type":"journal_article","issue":"30","abstract":[{"lang":"eng","text":"Attachment of adhesive molecules on cell culture surfaces to restrict cell adhesion to defined areas and shapes has been vital for the progress of in vitro research. In currently existing patterning methods, a combination of pattern properties such as stability, precision, specificity, high-throughput outcome, and spatiotemporal control is highly desirable but challenging to achieve. Here, we introduce a versatile and high-throughput covalent photoimmobilization technique, comprising a light-dose-dependent patterning step and a subsequent functionalization of the pattern via click chemistry. This two-step process is feasible on arbitrary surfaces and allows for generation of sustainable patterns and gradients. The method is validated in different biological systems by patterning adhesive ligands on cell-repellent surfaces, thereby constraining the growth and migration of cells to the designated areas. We then implement a sequential photopatterning approach by adding a second switchable patterning step, allowing for spatiotemporal control over two distinct surface patterns. As a proof of concept, we reconstruct the dynamics of the tip/stalk cell switch during angiogenesis. Our results show that the spatiotemporal control provided by our “sequential photopatterning” system is essential for mimicking dynamic biological processes and that our innovative approach has great potential for further applications in cell science."}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"9822","intvolume":" 13","ddc":["620","570"],"status":"public","title":"Sequential and switchable patterning for studying cellular processes under spatiotemporal control","file":[{"checksum":"b043a91d9f9200e467b970b692687ed3","success":1,"date_updated":"2021-08-09T09:44:03Z","date_created":"2021-08-09T09:44:03Z","relation":"main_file","file_id":"9833","file_size":7123293,"content_type":"application/pdf","creator":"asandaue","access_level":"open_access","file_name":"2021_ACSAppliedMaterialsAndInterfaces_Zisis.pdf"}],"oa_version":"Published Version","scopus_import":"1","article_processing_charge":"Yes (in subscription journal)","has_accepted_license":"1","day":"04","citation":{"short":"T. Zisis, J. Schwarz, M. Balles, M. Kretschmer, M. Nemethova, R.P. Chait, R. Hauschild, J. Lange, C.C. Guet, M.K. Sixt, S. Zahler, ACS Applied Materials and Interfaces 13 (2021) 35545–35560.","mla":"Zisis, Themistoklis, et al. “Sequential and Switchable Patterning for Studying Cellular Processes under Spatiotemporal Control.” ACS Applied Materials and Interfaces, vol. 13, no. 30, American Chemical Society, 2021, pp. 35545–35560, doi:10.1021/acsami.1c09850.","chicago":"Zisis, Themistoklis, Jan Schwarz, Miriam Balles, Maibritt Kretschmer, Maria Nemethova, Remy P Chait, Robert Hauschild, et al. “Sequential and Switchable Patterning for Studying Cellular Processes under Spatiotemporal Control.” ACS Applied Materials and Interfaces. American Chemical Society, 2021. https://doi.org/10.1021/acsami.1c09850.","ama":"Zisis T, Schwarz J, Balles M, et al. Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. 2021;13(30):35545–35560. doi:10.1021/acsami.1c09850","ieee":"T. Zisis et al., “Sequential and switchable patterning for studying cellular processes under spatiotemporal control,” ACS Applied Materials and Interfaces, vol. 13, no. 30. American Chemical Society, pp. 35545–35560, 2021.","apa":"Zisis, T., Schwarz, J., Balles, M., Kretschmer, M., Nemethova, M., Chait, R. P., … Zahler, S. (2021). Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. American Chemical Society. https://doi.org/10.1021/acsami.1c09850","ista":"Zisis T, Schwarz J, Balles M, Kretschmer M, Nemethova M, Chait RP, Hauschild R, Lange J, Guet CC, Sixt MK, Zahler S. 2021. Sequential and switchable patterning for studying cellular processes under spatiotemporal control. ACS Applied Materials and Interfaces. 13(30), 35545–35560."},"publication":"ACS Applied Materials and Interfaces","page":"35545–35560","article_type":"original","date_published":"2021-08-04T00:00:00Z"},{"article_number":"e68876","author":[{"full_name":"Batra, Aditi","last_name":"Batra","first_name":"Aditi"},{"full_name":"Römhild, Roderich","orcid":"0000-0001-9480-5261","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","last_name":"Römhild","first_name":"Roderich"},{"last_name":"Rousseau","first_name":"Emilie","full_name":"Rousseau, Emilie"},{"full_name":"Franzenburg, Sören","first_name":"Sören","last_name":"Franzenburg"},{"full_name":"Niemann, Stefan","first_name":"Stefan","last_name":"Niemann"},{"full_name":"Schulenburg, Hinrich","last_name":"Schulenburg","first_name":"Hinrich"}],"date_updated":"2023-08-11T10:26:29Z","date_created":"2021-07-28T13:36:57Z","volume":10,"year":"2021","acknowledgement":"We would like to thank Leif Tueffers and João Botelho for discussions and suggestions as well as Kira Haas and Julia Bunk for technical support. We acknowledge financial support from the German Science Foundation (grant SCHU 1415/12-2 to HS, and funding under Germany’s Excellence Strategy EXC 2167–390884018 as well as the Research Training Group 2501 TransEvo to HS and SN), the Max Planck Society (IMPRS scholarship to AB; Max-Planck fellowship to HS), and the Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG, to HS and SN). This work was further supported by the German Science Foundation Research Infrastructure NGS_CC (project 407495230) as part of the Next Generation Sequencing Competence Network (project 423957469). NGS analyses were carried out at the Competence Centre for Genomic Analysis Kiel (CCGA Kiel).","pmid":1,"publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"CaGu"}],"month":"07","publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/elife.68876","language":[{"iso":"eng"}],"external_id":{"isi":["000692027800001"],"pmid":["34318749"]},"main_file_link":[{"url":"https://doi.org/10.7554/eLife.68876","open_access":"1"}],"oa":1,"quality_controlled":"1","isi":1,"abstract":[{"text":"Evolutionary adaptation is a major source of antibiotic resistance in bacterial pathogens. Evolution-informed therapy aims to constrain resistance by accounting for bacterial evolvability. Sequential treatments with antibiotics that target different bacterial processes were previously shown to limit adaptation through genetic resistance trade-offs and negative hysteresis. Treatment with homogeneous sets of antibiotics is generally viewed to be disadvantageous, as it should rapidly lead to cross-resistance. We here challenged this assumption by determining the evolutionary response of Pseudomonas aeruginosa to experimental sequential treatments involving both heterogenous and homogeneous antibiotic sets. To our surprise, we found that fast switching between only β-lactam antibiotics resulted in increased extinction of bacterial populations. We demonstrate that extinction is favored by low rates of spontaneous resistance emergence and low levels of spontaneous cross-resistance among the antibiotics in sequence. The uncovered principles may help to guide the optimized use of available antibiotics in highly potent, evolution-informed treatment designs.","lang":"eng"}],"type":"journal_article","oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"9746","title":"High potency of sequential therapy with only beta-lactam antibiotics","status":"public","intvolume":" 10","day":"28","article_processing_charge":"No","scopus_import":"1","date_published":"2021-07-28T00:00:00Z","publication":"eLife","citation":{"apa":"Batra, A., Römhild, R., Rousseau, E., Franzenburg, S., Niemann, S., & Schulenburg, H. (2021). High potency of sequential therapy with only beta-lactam antibiotics. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.68876","ieee":"A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, and H. Schulenburg, “High potency of sequential therapy with only beta-lactam antibiotics,” eLife, vol. 10. eLife Sciences Publications, 2021.","ista":"Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. 2021. High potency of sequential therapy with only beta-lactam antibiotics. eLife. 10, e68876.","ama":"Batra A, Römhild R, Rousseau E, Franzenburg S, Niemann S, Schulenburg H. High potency of sequential therapy with only beta-lactam antibiotics. eLife. 2021;10. doi:10.7554/elife.68876","chicago":"Batra, Aditi, Roderich Römhild, Emilie Rousseau, Sören Franzenburg, Stefan Niemann, and Hinrich Schulenburg. “High Potency of Sequential Therapy with Only Beta-Lactam Antibiotics.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.68876.","short":"A. Batra, R. Römhild, E. Rousseau, S. Franzenburg, S. Niemann, H. Schulenburg, ELife 10 (2021).","mla":"Batra, Aditi, et al. “High Potency of Sequential Therapy with Only Beta-Lactam Antibiotics.” ELife, vol. 10, e68876, eLife Sciences Publications, 2021, doi:10.7554/elife.68876."},"article_type":"original"},{"abstract":[{"text":"Erythropoietin enhances oxygen delivery and reduces hypoxia-induced cell death, but its pro-thrombotic activity is problematic for use of erythropoietin in treating hypoxia. We constructed a fusion protein that stimulates red blood cell production and neuroprotection without triggering platelet production, a marker for thrombosis. The protein consists of an anti-glycophorin A nanobody and an erythropoietin mutant (L108A). The mutation reduces activation of erythropoietin receptor homodimers that induce erythropoiesis and thrombosis, but maintains the tissue-protective signaling. The binding of the nanobody element to glycophorin A rescues homodimeric erythropoietin receptor activation on red blood cell precursors. In a cell proliferation assay, the fusion protein is active at 10−14 M, allowing an estimate of the number of receptor–ligand complexes needed for signaling. This fusion protein stimulates erythroid cell proliferation in vitro and in mice, and shows neuroprotective activity in vitro. Our erythropoietin fusion protein presents a novel molecule for treating hypoxia.","lang":"eng"}],"type":"journal_article","oa_version":"Published Version","status":"public","title":"Rational engineering of an erythropoietin fusion protein to treat hypoxia","intvolume":" 34","_id":"10363","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","day":"01","article_processing_charge":"No","scopus_import":"1","date_published":"2021-11-01T00:00:00Z","article_type":"original","publication":"Protein Engineering, Design and Selection","citation":{"chicago":"Lee, Jungmin, Andyna Vernet, Nathalie Gruber, Kasia M. Kready, Devin R. Burrill, Jeffrey C. Way, and Pamela A. Silver. “Rational Engineering of an Erythropoietin Fusion Protein to Treat Hypoxia.” Protein Engineering, Design and Selection. Oxford University Press, 2021. https://doi.org/10.1093/protein/gzab025.","short":"J. Lee, A. Vernet, N. Gruber, K.M. Kready, D.R. Burrill, J.C. Way, P.A. Silver, Protein Engineering, Design and Selection 34 (2021).","mla":"Lee, Jungmin, et al. “Rational Engineering of an Erythropoietin Fusion Protein to Treat Hypoxia.” Protein Engineering, Design and Selection, vol. 34, gzab025, Oxford University Press, 2021, doi:10.1093/protein/gzab025.","apa":"Lee, J., Vernet, A., Gruber, N., Kready, K. M., Burrill, D. R., Way, J. C., & Silver, P. A. (2021). Rational engineering of an erythropoietin fusion protein to treat hypoxia. Protein Engineering, Design and Selection. Oxford University Press. https://doi.org/10.1093/protein/gzab025","ieee":"J. Lee et al., “Rational engineering of an erythropoietin fusion protein to treat hypoxia,” Protein Engineering, Design and Selection, vol. 34. Oxford University Press, 2021.","ista":"Lee J, Vernet A, Gruber N, Kready KM, Burrill DR, Way JC, Silver PA. 2021. Rational engineering of an erythropoietin fusion protein to treat hypoxia. Protein Engineering, Design and Selection. 34, gzab025.","ama":"Lee J, Vernet A, Gruber N, et al. Rational engineering of an erythropoietin fusion protein to treat hypoxia. Protein Engineering, Design and Selection. 2021;34. doi:10.1093/protein/gzab025"},"article_number":"gzab025","date_created":"2021-11-28T23:01:28Z","date_updated":"2023-08-14T13:01:38Z","volume":34,"author":[{"full_name":"Lee, Jungmin","last_name":"Lee","first_name":"Jungmin"},{"full_name":"Vernet, Andyna","last_name":"Vernet","first_name":"Andyna"},{"full_name":"Gruber, Nathalie","first_name":"Nathalie","last_name":"Gruber","id":"2C9C8316-AA17-11E9-B5C2-8BC2E5697425"},{"full_name":"Kready, Kasia M.","first_name":"Kasia M.","last_name":"Kready"},{"full_name":"Burrill, Devin R.","first_name":"Devin R.","last_name":"Burrill"},{"full_name":"Way, Jeffrey C.","last_name":"Way","first_name":"Jeffrey C."},{"full_name":"Silver, Pamela A.","last_name":"Silver","first_name":"Pamela A."}],"publication_status":"published","department":[{"_id":"CaGu"}],"publisher":"Oxford University Press","year":"2021","acknowledgement":"This work was supported by funds from the Wyss Institute for Biologically Inspired Engineering and the Boston Biomedical Innovation Center (Pilot Award 112475; Drive Award U54HL119145). J.L., K.M.K., D.R.B., J.C.W. and P.A.S. were supported by the Harvard Medical School Department of Systems Biology. J.C.W. was further supported by the Harvard Medical School Laboratory of Systems Pharmacology. A.V., D.R.B. and P.A.S. were further supported by the Wyss Institute for Biologically Inspired Engineering. N.G.G. was sponsored by the Army Research Office under Grant Number W911NF-17-2-0092. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the Army Research Office or the U.S. Government. The U.S. Government is authorized to reproduce and distribute reprints for Government purposes notwithstanding any copyright notation herein. We sincerely thank Amanda Graveline and the Wyss Institute at Harvard for their scientific support.","pmid":1,"month":"11","publication_identifier":{"issn":["1741-0126"],"eissn":["1741-0134"]},"language":[{"iso":"eng"}],"doi":"10.1093/protein/gzab025","isi":1,"quality_controlled":"1","oa":1,"main_file_link":[{"url":"https://doi.org/10.1093/protein/gzab025","open_access":"1"}],"external_id":{"pmid":["34725710"],"isi":["000746596900001"]}},{"file_date_updated":"2021-03-23T10:12:58Z","ec_funded":1,"license":"https://creativecommons.org/licenses/by/4.0/","article_number":"e65993","author":[{"orcid":"0000-0002-1391-8377","id":"3ABC5BA6-F248-11E8-B48F-1D18A9856A87","last_name":"Nagy-Staron","first_name":"Anna A","full_name":"Nagy-Staron, Anna A"},{"full_name":"Tomasek, Kathrin","orcid":"0000-0003-3768-877X","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","last_name":"Tomasek","first_name":"Kathrin"},{"last_name":"Caruso Carter","first_name":"Caroline","full_name":"Caruso Carter, Caroline"},{"full_name":"Sonnleitner, Elisabeth","last_name":"Sonnleitner","first_name":"Elisabeth"},{"last_name":"Kavcic","first_name":"Bor","orcid":"0000-0001-6041-254X","id":"350F91D2-F248-11E8-B48F-1D18A9856A87","full_name":"Kavcic, Bor"},{"full_name":"Paixão, Tiago","first_name":"Tiago","last_name":"Paixão"},{"full_name":"Guet, Calin C","last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"record":[{"id":"8951","relation":"research_data","status":"public"}]},"date_updated":"2024-02-21T12:41:57Z","date_created":"2021-03-23T10:11:46Z","volume":10,"year":"2021","acknowledgement":"We thank J Bollback, L Hurst, M Lagator, C Nizak, O Rivoire, M Savageau, G Tkacik, and B Vicozo\r\nfor helpful discussions; A Dolinar and A Greshnova for technical assistance; T Bollenbach for supplying the strain JW0336; C Rusnac, and members of the Guet lab for comments. 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˚\r\n628377 (ANS) and an Austrian Science Fund (FWF) grant n˚ I 3901-B32 (CCG).","publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"GaTk"},{"_id":"CaGu"}],"month":"03","publication_identifier":{"issn":["2050-084X"]},"doi":"10.7554/elife.65993","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000631050900001"]},"quality_controlled":"1","isi":1,"project":[{"call_identifier":"FP7","name":"The Systems Biology of Transcriptional Read-Through in Bacteria: from Synthetic Networks to Genomic Studies","_id":"2517526A-B435-11E9-9278-68D0E5697425","grant_number":"628377"},{"name":"CyberCircuits: Cybergenetic circuits to test composability of gene networks","call_identifier":"FWF","_id":"268BFA92-B435-11E9-9278-68D0E5697425","grant_number":"I03901"}],"abstract":[{"text":"Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic GRN to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one GRN with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit (TU) within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual TUs, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of GRNs.","lang":"eng"}],"type":"journal_article","file":[{"relation":"main_file","file_id":"9284","checksum":"3c2f44058c2dd45a5a1027f09d263f8e","success":1,"date_updated":"2021-03-23T10:12:58Z","date_created":"2021-03-23T10:12:58Z","access_level":"open_access","file_name":"elife-65993-v2.pdf","file_size":1390469,"content_type":"application/pdf","creator":"bkavcic"}],"oa_version":"Published Version","_id":"9283","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"status":"public","title":"Local genetic context shapes the function of a gene regulatory network","intvolume":" 10","day":"08","has_accepted_license":"1","article_processing_charge":"Yes","keyword":["Genetics and Molecular Biology"],"date_published":"2021-03-08T00:00:00Z","publication":"eLife","citation":{"short":"A.A. Nagy-Staron, K. Tomasek, C. Caruso Carter, E. Sonnleitner, B. Kavcic, T. Paixão, C.C. Guet, ELife 10 (2021).","mla":"Nagy-Staron, Anna A., et al. “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” ELife, vol. 10, e65993, eLife Sciences Publications, 2021, doi:10.7554/elife.65993.","chicago":"Nagy-Staron, Anna A, Kathrin Tomasek, Caroline Caruso Carter, Elisabeth Sonnleitner, Bor Kavcic, Tiago Paixão, and Calin C Guet. “Local Genetic Context Shapes the Function of a Gene Regulatory Network.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.65993.","ama":"Nagy-Staron AA, Tomasek K, Caruso Carter C, et al. Local genetic context shapes the function of a gene regulatory network. eLife. 2021;10. doi:10.7554/elife.65993","apa":"Nagy-Staron, A. A., Tomasek, K., Caruso Carter, C., Sonnleitner, E., Kavcic, B., Paixão, T., & Guet, C. C. (2021). Local genetic context shapes the function of a gene regulatory network. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.65993","ieee":"A. A. Nagy-Staron et al., “Local genetic context shapes the function of a gene regulatory network,” eLife, vol. 10. eLife Sciences Publications, 2021.","ista":"Nagy-Staron AA, Tomasek K, Caruso Carter C, Sonnleitner E, Kavcic B, Paixão T, Guet CC. 2021. Local genetic context shapes the function of a gene regulatory network. eLife. 10, e65993."},"article_type":"original"}]