[{"publication":"PLoS Biology","title":"Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila","pmid":1,"ddc":["570"],"related_material":{"link":[{"url":"https://www.biorxiv.org/content/10.1101/2020.09.18.301481","relation":"earlier_version"},{"description":"News on the ISTA Website","relation":"press_release","url":"https://ista.ac.at/en/news/resisting-the-pressure/"}],"record":[{"id":"8557","relation":"earlier_version","status":"public"},{"id":"11193","status":"public","relation":"dissertation_contains"}]},"oa":1,"_id":"10614","project":[{"_id":"253B6E48-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P29638","name":"Drosophila TNFa´s Funktion in Immunzellen"},{"grant_number":"24800","name":"Tissue barrier penetration is crucial for immunity and metastasis","_id":"26199CA4-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","_id":"2536F660-B435-11E9-9278-68D0E5697425","name":"Investigating the role of transporters in invasive migration through junctions","grant_number":"334077"}],"publication_status":"published","abstract":[{"text":"The infiltration of immune cells into tissues underlies the establishment of tissue-resident macrophages and responses to infections and tumors. Yet the mechanisms immune cells utilize to negotiate tissue barriers in living organisms are not well understood, and a role for cortical actin has not been examined. Here, we find that the tissue invasion of Drosophila macrophages, also known as plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated by the Drosophila member of the fos proto oncogene transcription factor family (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances F-actin levels around the entire macrophage surface by increasing mRNA levels of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking filamin Cheerio, which are themselves required for invasion. Both the filamin and the tetraspanin enhance the cortical activity of Rho1 and the formin Diaphanous and thus the assembly of cortical actin, which is a critical function since expressing a dominant active form of Diaphanous can rescue the Dfos macrophage invasion defect. In vivo imaging shows that Dfos enhances the efficiency of the initial phases of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program in macrophages counteracts the constraint produced by the tension of surrounding tissues and buffers the properties of the macrophage nucleus from affecting tissue entry. We thus identify strengthening the cortical actin cytoskeleton through Dfos as a key process allowing efficient forward movement of an immune cell into surrounding tissues. ","lang":"eng"}],"citation":{"ieee":"V. Belyaeva <i>et al.</i>, “Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila,” <i>PLoS Biology</i>, vol. 20, no. 1. Public Library of Science, p. e3001494, 2022.","ama":"Belyaeva V, Wachner S, György A, et al. Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. <i>PLoS Biology</i>. 2022;20(1):e3001494. doi:<a href=\"https://doi.org/10.1371/journal.pbio.3001494\">10.1371/journal.pbio.3001494</a>","short":"V. Belyaeva, S. Wachner, A. György, S. Emtenani, I. Gridchyn, M. Akhmanova, M. Linder, M. Roblek, M. Sibilia, D.E. Siekhaus, PLoS Biology 20 (2022) e3001494.","chicago":"Belyaeva, Vera, Stephanie Wachner, Attila György, Shamsi Emtenani, Igor Gridchyn, Maria Akhmanova, M Linder, Marko Roblek, M Sibilia, and Daria E Siekhaus. “Fos Regulates Macrophage Infiltration against Surrounding Tissue Resistance by a Cortical Actin-Based Mechanism in Drosophila.” <i>PLoS Biology</i>. Public Library of Science, 2022. <a href=\"https://doi.org/10.1371/journal.pbio.3001494\">https://doi.org/10.1371/journal.pbio.3001494</a>.","ista":"Belyaeva V, Wachner S, György A, Emtenani S, Gridchyn I, Akhmanova M, Linder M, Roblek M, Sibilia M, Siekhaus DE. 2022. Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. PLoS Biology. 20(1), e3001494.","mla":"Belyaeva, Vera, et al. “Fos Regulates Macrophage Infiltration against Surrounding Tissue Resistance by a Cortical Actin-Based Mechanism in Drosophila.” <i>PLoS Biology</i>, vol. 20, no. 1, Public Library of Science, 2022, p. e3001494, doi:<a href=\"https://doi.org/10.1371/journal.pbio.3001494\">10.1371/journal.pbio.3001494</a>.","apa":"Belyaeva, V., Wachner, S., György, A., Emtenani, S., Gridchyn, I., Akhmanova, M., … Siekhaus, D. E. (2022). Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila. <i>PLoS Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pbio.3001494\">https://doi.org/10.1371/journal.pbio.3001494</a>"},"quality_controlled":"1","author":[{"first_name":"Vera","last_name":"Belyaeva","id":"47F080FE-F248-11E8-B48F-1D18A9856A87","full_name":"Belyaeva, Vera"},{"id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87","full_name":"Wachner, Stephanie","last_name":"Wachner","first_name":"Stephanie"},{"full_name":"György, Attila","orcid":"0000-0002-1819-198X","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","first_name":"Attila","last_name":"György"},{"full_name":"Emtenani, Shamsi","orcid":"0000-0001-6981-6938","id":"49D32318-F248-11E8-B48F-1D18A9856A87","first_name":"Shamsi","last_name":"Emtenani"},{"id":"4B60654C-F248-11E8-B48F-1D18A9856A87","full_name":"Gridchyn, Igor","orcid":"0000-0002-1807-1929","last_name":"Gridchyn","first_name":"Igor"},{"orcid":"0000-0003-1522-3162","full_name":"Akhmanova, Maria","id":"3425EC26-F248-11E8-B48F-1D18A9856A87","last_name":"Akhmanova","first_name":"Maria"},{"full_name":"Linder, M","first_name":"M","last_name":"Linder"},{"full_name":"Roblek, Marko","orcid":"0000-0001-9588-1389","id":"3047D808-F248-11E8-B48F-1D18A9856A87","last_name":"Roblek","first_name":"Marko"},{"first_name":"M","last_name":"Sibilia","full_name":"Sibilia, M"},{"id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","full_name":"Siekhaus, Daria E","first_name":"Daria E","last_name":"Siekhaus"}],"tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"year":"2022","intvolume":"        20","isi":1,"date_created":"2022-01-12T10:18:17Z","month":"01","status":"public","issue":"1","volume":20,"file_date_updated":"2022-01-12T13:50:04Z","publisher":"Public Library of Science","article_type":"original","ec_funded":1,"acknowledged_ssus":[{"_id":"LifeSc"}],"doi":"10.1371/journal.pbio.3001494","language":[{"iso":"eng"}],"has_accepted_license":"1","department":[{"_id":"DaSi"},{"_id":"JoCs"}],"acknowledgement":"We thank the following for their contributions: Plasmids were supplied by the Drosophila Genomics Resource Center (NIH 2P40OD010949-10A1); fly stocks were provided by K. Brueckner, B. Stramer, M. Uhlirova, O. Schuldiner, the Bloomington Drosophila Stock Center (NIH P40OD018537) and the Vienna Drosophila Resource Center, FlyBase for essential genomic information, and the BDGP in situ database for data. For antibodies, we thank the Developmental Studies Hybridoma Bank, which was created by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the NIH and is maintained at the University of Iowa, as well as J. Zeitlinger for her generous gift of Dfos antibody. We thank the Vienna BioCenter Core Facilities for RNA sequencing and analysis and the Life Scientific Service Units at IST Austria for technical support and assistance with microscopy and FACS analysis. We thank C. P. Heisenberg, P. Martin, M. Sixt, and Siekhaus group members for discussions and T. Hurd, A. Ratheesh, and P. Rangan for comments on the manuscript.","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","type":"journal_article","date_updated":"2024-03-25T23:30:15Z","oa_version":"Published Version","day":"06","publication_identifier":{"issn":["1544-9173"],"eissn":["1545-7885"]},"scopus_import":"1","date_published":"2022-01-06T00:00:00Z","file":[{"date_created":"2022-01-12T13:50:04Z","relation":"main_file","creator":"cchlebak","content_type":"application/pdf","file_size":5426932,"file_id":"10615","date_updated":"2022-01-12T13:50:04Z","success":1,"access_level":"open_access","checksum":"f454212a5522a7818ba4b2892315c478","file_name":"2022_PLOSBio_Belyaeva.pdf"}],"external_id":{"pmid":["34990456"],"isi":["000971223700001"]},"page":"e3001494"},{"main_file_link":[{"url":"https://www.sciencedirect.com/science/article/pii/S1534580721009497","open_access":"1"}],"citation":{"apa":"Gaertner, F., Reis-Rodrigues, P., de Vries, I., Hons, M., Aguilera, J., Riedl, M., … Sixt, M. K. (2022). WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. <i>Developmental Cell</i>. Cell Press ; Elsevier. <a href=\"https://doi.org/10.1016/j.devcel.2021.11.024\">https://doi.org/10.1016/j.devcel.2021.11.024</a>","mla":"Gaertner, Florian, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” <i>Developmental Cell</i>, vol. 57, no. 1, Cell Press ; Elsevier, 2022, p. 47–62.e9, doi:<a href=\"https://doi.org/10.1016/j.devcel.2021.11.024\">10.1016/j.devcel.2021.11.024</a>.","ista":"Gaertner F, Reis-Rodrigues P, de Vries I, Hons M, Aguilera J, Riedl M, Leithner AF, Tasciyan S, Kopf A, Merrin J, Zheden V, Kaufmann W, Hauschild R, Sixt MK. 2022. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. Developmental Cell. 57(1), 47–62.e9.","chicago":"Gaertner, Florian, Patricia Reis-Rodrigues, Ingrid de Vries, Miroslav Hons, Juan Aguilera, Michael Riedl, Alexander F Leithner, et al. “WASp Triggers Mechanosensitive Actin Patches to Facilitate Immune Cell Migration in Dense Tissues.” <i>Developmental Cell</i>. Cell Press ; Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.devcel.2021.11.024\">https://doi.org/10.1016/j.devcel.2021.11.024</a>.","short":"F. Gaertner, P. Reis-Rodrigues, I. de Vries, M. Hons, J. Aguilera, M. Riedl, A.F. Leithner, S. Tasciyan, A. Kopf, J. Merrin, V. Zheden, W. Kaufmann, R. Hauschild, M.K. Sixt, Developmental Cell 57 (2022) 47–62.e9.","ama":"Gaertner F, Reis-Rodrigues P, de Vries I, et al. WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues. <i>Developmental Cell</i>. 2022;57(1):47-62.e9. doi:<a href=\"https://doi.org/10.1016/j.devcel.2021.11.024\">10.1016/j.devcel.2021.11.024</a>","ieee":"F. Gaertner <i>et al.</i>, “WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues,” <i>Developmental Cell</i>, vol. 57, no. 1. Cell Press ; Elsevier, p. 47–62.e9, 2022."},"author":[{"full_name":"Gaertner, Florian","last_name":"Gaertner","first_name":"Florian"},{"first_name":"Patricia","last_name":"Reis-Rodrigues","full_name":"Reis-Rodrigues, Patricia"},{"id":"4C7D837E-F248-11E8-B48F-1D18A9856A87","full_name":"De Vries, Ingrid","last_name":"De Vries","first_name":"Ingrid"},{"id":"4167FE56-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6625-3348","full_name":"Hons, Miroslav","first_name":"Miroslav","last_name":"Hons"},{"first_name":"Juan","last_name":"Aguilera","full_name":"Aguilera, Juan"},{"id":"3BE60946-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4844-6311","full_name":"Riedl, Michael","first_name":"Michael","last_name":"Riedl"},{"last_name":"Leithner","first_name":"Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F","orcid":"0000-0002-1073-744X"},{"last_name":"Tasciyan","first_name":"Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","full_name":"Tasciyan, Saren","orcid":"0000-0003-1671-393X"},{"last_name":"Kopf","first_name":"Aglaja","orcid":"0000-0002-2187-6656","full_name":"Kopf, Aglaja","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-5145-4609","full_name":"Merrin, Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","first_name":"Jack","last_name":"Merrin"},{"first_name":"Vanessa","last_name":"Zheden","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","full_name":"Zheden, Vanessa","orcid":"0000-0002-9438-4783"},{"full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","last_name":"Kaufmann","first_name":"Walter"},{"first_name":"Robert","last_name":"Hauschild","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K"}],"quality_controlled":"1","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"year":"2022","title":"WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues","publication":"Developmental Cell","pmid":1,"ddc":["570"],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12726"},{"relation":"dissertation_contains","status":"public","id":"14530"},{"id":"12401","status":"public","relation":"dissertation_contains"}]},"oa":1,"_id":"10703","project":[{"name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","grant_number":"747687","call_identifier":"H2020","_id":"260AA4E2-B435-11E9-9278-68D0E5697425"},{"name":"Cellular navigation along spatial gradients","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"publication_status":"published","abstract":[{"text":"When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes.","lang":"eng"}],"volume":57,"issue":"1","publisher":"Cell Press ; Elsevier","article_type":"original","intvolume":"        57","isi":1,"date_created":"2022-01-30T23:01:33Z","month":"01","status":"public","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_updated":"2024-03-25T23:30:12Z","type":"journal_article","oa_version":"Published Version","day":"10","ec_funded":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"EM-Fac"}],"language":[{"iso":"eng"}],"doi":"10.1016/j.devcel.2021.11.024","department":[{"_id":"MiSi"},{"_id":"EM-Fac"},{"_id":"NanoFab"},{"_id":"BjHo"}],"acknowledgement":"We thank N. Darwish-Miranda, F. Leite, F.P. Assen, and A. Eichner for advice and help with experiments. We thank J. Renkawitz, E. Kiermaier, A. Juanes Garcia, and M. Avellaneda for critical reading of the manuscript. We thank M. Driscoll for advice on fluorescent labeling of collagen gels. This research was supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by Molecular Biology Services/Lab Support Facility (LSF)/Bioimaging Facility/Electron Microscopy Facility. This work was funded by grants from the European Research Council ( CoG 724373 ) and the Austrian Science Foundation (FWF) to M.S. F.G. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 747687.","date_published":"2022-01-10T00:00:00Z","external_id":{"pmid":["34919802"],"isi":["000768933800005"]},"page":"47-62.e9","publication_identifier":{"eissn":["1878-1551"],"issn":["1534-5807"]},"scopus_import":"1"},{"project":[{"name":"Epidemics in ant societies on a chip","grant_number":"771402","_id":"2649B4DE-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"publication_status":"published","abstract":[{"lang":"eng","text":"Social insects are a common model to study disease dynamics in social animals. Even though pathogens should thrive in social insect colonies as the hosts engage in frequent social interactions, are closely related and live in a pathogen-rich environment, disease outbreaks are rare. This is because social insects have evolved mechanisms to keep pathogens at bay – and fight disease as a collective. Social insect colonies are often viewed as “superorganisms” with division of labor between reproductive “germ-like” queens and males and “somatic” workers, which together form an interdependent reproductive unit that parallels a multicellular body. Superorganisms possess a “social immune system” that comprises of collective disease defenses performed by the workers - summarized as “social immunity”. In social groups immunization (reduced susceptibility to a parasite upon secondary exposure to the same parasite) can e.g. be triggered by social interactions (“social immunization”). Social immunization can be caused by (i) asymptomatic low-level infections that are acquired during caregiving to a contagious individual that can give an immune boost, which can induce protection upon later encounter with the same pathogen (active immunization) or (ii) by transfer of immune effectors between individuals (passive immunization).\r\nIn the second chapter, I built up on a study that I co-authored that found that low-level infections can not only be protective, but also be costly and make the host more susceptible to detrimental superinfections after contact to a very dissimilar pathogen. I here now tested different degrees of phylogenetically-distant fungal strains of M. brunneum and M. robertsii in L. neglectus and can describe the occurrence of cross-protection of social immunization if the first and second pathogen are from the same level. Interestingly, low-level infections only provided protection when the first strain was less virulent than the second strain and elicited higher immune gene expression.\r\nIn the third and fourth chapters, I expanded on the role of social immunity in sexual selection, a so far unstudied field. I used the fungus Metarhizium robertsii and the ant Cardiocondyla obscurior as a model, as in this species mating occurs in the presence of workers and can be studied under laboratory conditions. Before males mate with virgin queens in the nest they engage in fierce combat over the access to their mating partners.\r\nFirst, I focused on male-male competition in the third chapter and found that fighting with a contagious male is costly as it can lead to contamination of the rival, but that workers can decrease the risk of disease contraction by performing sanitary care.\r\nIn the fourth chapter, I studied the effect of fungal infection on survival and mating success of sexuals (freshly emerged queens and males) and found that worker-performed sanitary care can buffer the negative effect that a pathogenic contagion would have on sexuals by spore removal from the exposed individuals. When social immunity was prevented and queens could contract spores from their mating partner, very low dosages led to negative consequences: their lifespan was reduced and they produced fewer offspring with poor immunocompetence compared to healthy queens. Interestingly, cohabitation with a late-stage infected male where no spore transfer was possible had a positive effect on offspring immunity – male offspring of mothers that apparently perceived an infected partner in their vicinity reacted more sensitively to fungal challenge than male offspring without paternal pathogen history."}],"title":"Pathogen-mediated sexual selection and immunization in ant colonies","ddc":["570"],"oa":1,"_id":"10727","year":"2022","citation":{"ieee":"S. Metzler, “Pathogen-mediated sexual selection and immunization in ant colonies,” Institute of Science and Technology Austria, 2022.","ama":"Metzler S. Pathogen-mediated sexual selection and immunization in ant colonies. 2022. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:10727\">10.15479/AT:ISTA:10727</a>","ista":"Metzler S. 2022. Pathogen-mediated sexual selection and immunization in ant colonies. Institute of Science and Technology Austria.","chicago":"Metzler, Sina. “Pathogen-Mediated Sexual Selection and Immunization in Ant Colonies.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/AT:ISTA:10727\">https://doi.org/10.15479/AT:ISTA:10727</a>.","short":"S. Metzler, Pathogen-Mediated Sexual Selection and Immunization in Ant Colonies, Institute of Science and Technology Austria, 2022.","apa":"Metzler, S. (2022). <i>Pathogen-mediated sexual selection and immunization in ant colonies</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:10727\">https://doi.org/10.15479/AT:ISTA:10727</a>","mla":"Metzler, Sina. <i>Pathogen-Mediated Sexual Selection and Immunization in Ant Colonies</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:10727\">10.15479/AT:ISTA:10727</a>."},"author":[{"last_name":"Metzler","first_name":"Sina","id":"48204546-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9547-2494","full_name":"Metzler, Sina"}],"date_created":"2022-02-04T15:45:12Z","month":"02","status":"public","degree_awarded":"PhD","file_date_updated":"2023-02-04T23:30:03Z","publisher":"Institute of Science and Technology Austria","acknowledged_ssus":[{"_id":"LifeSc"}],"ec_funded":1,"doi":"10.15479/AT:ISTA:10727","language":[{"iso":"eng"}],"has_accepted_license":"1","department":[{"_id":"GradSch"},{"_id":"SyCr"}],"type":"dissertation","date_updated":"2023-09-07T13:43:23Z","oa_version":"Published Version","day":"07","supervisor":[{"orcid":"0000-0002-2193-3868","full_name":"Cremer, Sylvia","id":"2F64EC8C-F248-11E8-B48F-1D18A9856A87","first_name":"Sylvia","last_name":"Cremer"}],"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","alternative_title":["ISTA Thesis"],"publication_identifier":{"issn":["2663-337X"]},"date_published":"2022-02-07T00:00:00Z","file":[{"file_id":"10728","date_updated":"2023-02-03T23:30:03Z","access_level":"closed","file_name":"Thesis_Sina_Metzler.docx","checksum":"47ba18bb270dd6cc266e0a3f7c69d0e4","date_created":"2022-02-04T15:36:12Z","embargo_to":"open_access","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","creator":"smetzler","file_size":6757886},{"date_created":"2022-02-04T15:36:43Z","relation":"main_file","embargo":"2023-02-02","file_size":6314921,"content_type":"application/pdf","creator":"smetzler","date_updated":"2023-02-03T23:30:03Z","file_id":"10730","access_level":"open_access","file_name":"Thesis_Sina_Metzler_A2.pdf","checksum":"f3ec07d5d6b20ae6e46bfeedebce9027"},{"file_id":"10742","date_updated":"2023-02-04T23:30:03Z","access_level":"open_access","checksum":"dedd14b7be7a75d63018dbfc68dd8113","file_name":"Thesis_Sina_Metzler_print.pdf","date_created":"2022-02-07T10:35:02Z","relation":"main_file","embargo":"2023-02-02","creator":"smetzler","content_type":"application/pdf","file_size":6882557}]},{"date_published":"2022-07-07T00:00:00Z","file":[{"file_name":"2023_OxfordOpenNeuroscience_Hansen.pdf","checksum":"822e76e056c07099d1fb27d1ece5941b","access_level":"open_access","success":1,"date_updated":"2023-08-16T08:00:30Z","file_id":"14061","content_type":"application/pdf","creator":"dernst","file_size":4846551,"relation":"main_file","date_created":"2023-08-16T08:00:30Z"}],"publication_identifier":{"eissn":["2753-149X"]},"day":"07","type":"journal_article","date_updated":"2023-11-30T10:55:12Z","oa_version":"Published Version","article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledgement":"A.H.H. was a recipient of a DOC Fellowship (24812) of the Austrian Academy of Sciences. This work also received support from IST Austria institutional funds; the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007–2013) under REA grant agreement No 618444 to S.H.\r\nAPC funding was obtained by IST Austria institutional funds.\r\nWe thank A. Sommer and C. Czepe (VBCF GmbH, NGS Unit), L. Andersen, J. Sonntag and J. Renno for technical support and/or initial experiments; M. Sixt, J. Nimpf and all members of the Hippenmeyer lab for discussion. This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics Facility, Lab Support Facility and Preclinical Facility.","doi":"10.1093/oons/kvac009","language":[{"iso":"eng"}],"department":[{"_id":"SiHi"},{"_id":"BjHo"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"has_accepted_license":"1","ec_funded":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"Bio"}],"publisher":"Oxford Academic","article_type":"original","file_date_updated":"2023-08-16T08:00:30Z","issue":"1","volume":1,"article_number":"kvac009","status":"public","date_created":"2022-02-25T07:52:11Z","month":"07","intvolume":"         1","year":"2022","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"author":[{"full_name":"Hansen, Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","last_name":"Hansen"},{"orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","first_name":"Florian"},{"last_name":"Riedl","first_name":"Michael","id":"3BE60946-F248-11E8-B48F-1D18A9856A87","full_name":"Riedl, Michael","orcid":"0000-0003-4844-6311"},{"last_name":"Streicher","first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen"},{"last_name":"Heger","first_name":"Anna-Magdalena","full_name":"Heger, Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87"},{"id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne","first_name":"Susanne","last_name":"Laukoter"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer"},{"full_name":"Nicolas, Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","last_name":"Nicolas","first_name":"Armel"},{"full_name":"Hof, Björn","orcid":"0000-0003-2057-2754","id":"3A374330-F248-11E8-B48F-1D18A9856A87","first_name":"Björn","last_name":"Hof"},{"first_name":"Li Huei","last_name":"Tsai","full_name":"Tsai, Li Huei"},{"first_name":"Thomas","last_name":"Rülicke","full_name":"Rülicke, Thomas"},{"first_name":"Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"}],"quality_controlled":"1","citation":{"ama":"Hansen AH, Pauler F, Riedl M, et al. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. 2022;1(1). doi:<a href=\"https://doi.org/10.1093/oons/kvac009\">10.1093/oons/kvac009</a>","ieee":"A. H. Hansen <i>et al.</i>, “Tissue-wide effects override cell-intrinsic gene function in radial neuron migration,” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1. Oxford Academic, 2022.","ista":"Hansen AH, Pauler F, Riedl M, Streicher C, Heger A-M, Laukoter S, Sommer CM, Nicolas A, Hof B, Tsai LH, Rülicke T, Hippenmeyer S. 2022. Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. Oxford Open Neuroscience. 1(1), kvac009.","chicago":"Hansen, Andi H, Florian Pauler, Michael Riedl, Carmen Streicher, Anna-Magdalena Heger, Susanne Laukoter, Christoph M Sommer, et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>. Oxford Academic, 2022. <a href=\"https://doi.org/10.1093/oons/kvac009\">https://doi.org/10.1093/oons/kvac009</a>.","short":"A.H. Hansen, F. Pauler, M. Riedl, C. Streicher, A.-M. Heger, S. Laukoter, C.M. Sommer, A. Nicolas, B. Hof, L.H. Tsai, T. Rülicke, S. Hippenmeyer, Oxford Open Neuroscience 1 (2022).","mla":"Hansen, Andi H., et al. “Tissue-Wide Effects Override Cell-Intrinsic Gene Function in Radial Neuron Migration.” <i>Oxford Open Neuroscience</i>, vol. 1, no. 1, kvac009, Oxford Academic, 2022, doi:<a href=\"https://doi.org/10.1093/oons/kvac009\">10.1093/oons/kvac009</a>.","apa":"Hansen, A. H., Pauler, F., Riedl, M., Streicher, C., Heger, A.-M., Laukoter, S., … Hippenmeyer, S. (2022). Tissue-wide effects override cell-intrinsic gene function in radial neuron migration. <i>Oxford Open Neuroscience</i>. Oxford Academic. <a href=\"https://doi.org/10.1093/oons/kvac009\">https://doi.org/10.1093/oons/kvac009</a>"},"publication_status":"published","abstract":[{"lang":"eng","text":"The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation depends on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps, regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not clear. Here we utilized mosaic analysis with double markers (MADM) technology to either sparsely or globally delete gene function, followed by quantitative single-cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically affects the overall migration phenotype of individual cortical projection neurons. In a broader context, our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development in particular, and neurological diseases in general."}],"project":[{"call_identifier":"FP7","_id":"25D61E48-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Cerebral Cortex Development","grant_number":"618444"},{"_id":"2625A13E-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms of Radial Neuronal Migration","grant_number":"24812"}],"related_material":{"record":[{"id":"12726","relation":"dissertation_contains","status":"public"},{"relation":"dissertation_contains","status":"public","id":"14530"}]},"ddc":["570"],"oa":1,"_id":"10791","title":"Tissue-wide effects override cell-intrinsic gene function in radial neuron migration","publication":"Oxford Open Neuroscience"},{"project":[{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Cellular navigation along spatial gradients","grant_number":"724373"}],"publication_status":"published","abstract":[{"lang":"eng","text":"Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion."}],"title":"Multitier mechanics control stromal adaptations in swelling lymph nodes","publication":"Nature Immunology","ddc":["570"],"oa":1,"_id":"9794","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"year":"2022","citation":{"ama":"Assen FP, Abe J, Hons M, et al. Multitier mechanics control stromal adaptations in swelling lymph nodes. <i>Nature Immunology</i>. 2022;23:1246-1255. doi:<a href=\"https://doi.org/10.1038/s41590-022-01257-4\">10.1038/s41590-022-01257-4</a>","ieee":"F. P. Assen <i>et al.</i>, “Multitier mechanics control stromal adaptations in swelling lymph nodes,” <i>Nature Immunology</i>, vol. 23. Springer Nature, pp. 1246–1255, 2022.","chicago":"Assen, Frank P, Jun Abe, Miroslav Hons, Robert Hauschild, Shayan Shamipour, Walter Kaufmann, Tommaso Costanzo, et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” <i>Nature Immunology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41590-022-01257-4\">https://doi.org/10.1038/s41590-022-01257-4</a>.","short":"F.P. Assen, J. Abe, M. Hons, R. Hauschild, S. Shamipour, W. Kaufmann, T. Costanzo, G. Krens, M. Brown, B. Ludewig, S. Hippenmeyer, C.-P.J. Heisenberg, W. Weninger, E.B. Hannezo, S.A. Luther, J.V. Stein, M.K. Sixt, Nature Immunology 23 (2022) 1246–1255.","ista":"Assen FP, Abe J, Hons M, Hauschild R, Shamipour S, Kaufmann W, Costanzo T, Krens G, Brown M, Ludewig B, Hippenmeyer S, Heisenberg C-PJ, Weninger W, Hannezo EB, Luther SA, Stein JV, Sixt MK. 2022. Multitier mechanics control stromal adaptations in swelling lymph nodes. Nature Immunology. 23, 1246–1255.","mla":"Assen, Frank P., et al. “Multitier Mechanics Control Stromal Adaptations in Swelling Lymph Nodes.” <i>Nature Immunology</i>, vol. 23, Springer Nature, 2022, pp. 1246–55, doi:<a href=\"https://doi.org/10.1038/s41590-022-01257-4\">10.1038/s41590-022-01257-4</a>.","apa":"Assen, F. P., Abe, J., Hons, M., Hauschild, R., Shamipour, S., Kaufmann, W., … Sixt, M. K. (2022). Multitier mechanics control stromal adaptations in swelling lymph nodes. <i>Nature Immunology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41590-022-01257-4\">https://doi.org/10.1038/s41590-022-01257-4</a>"},"quality_controlled":"1","author":[{"first_name":"Frank P","last_name":"Assen","id":"3A8E7F24-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3470-6119","full_name":"Assen, Frank P"},{"full_name":"Abe, Jun","last_name":"Abe","first_name":"Jun"},{"last_name":"Hons","first_name":"Miroslav","orcid":"0000-0002-6625-3348","full_name":"Hons, Miroslav","id":"4167FE56-F248-11E8-B48F-1D18A9856A87"},{"id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","full_name":"Hauschild, Robert","orcid":"0000-0001-9843-3522","first_name":"Robert","last_name":"Hauschild"},{"first_name":"Shayan","last_name":"Shamipour","full_name":"Shamipour, Shayan","id":"40B34FE2-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","first_name":"Walter","last_name":"Kaufmann"},{"first_name":"Tommaso","last_name":"Costanzo","full_name":"Costanzo, Tommaso","orcid":"0000-0001-9732-3815","id":"D93824F4-D9BA-11E9-BB12-F207E6697425"},{"full_name":"Krens, Gabriel","orcid":"0000-0003-4761-5996","id":"2B819732-F248-11E8-B48F-1D18A9856A87","first_name":"Gabriel","last_name":"Krens"},{"last_name":"Brown","first_name":"Markus","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","full_name":"Brown, Markus"},{"full_name":"Ludewig, Burkhard","first_name":"Burkhard","last_name":"Ludewig"},{"last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Weninger","first_name":"Wolfgang","full_name":"Weninger, Wolfgang"},{"first_name":"Edouard B","last_name":"Hannezo","full_name":"Hannezo, Edouard B","orcid":"0000-0001-6005-1561","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Sanjiv A.","last_name":"Luther","full_name":"Luther, Sanjiv A."},{"full_name":"Stein, Jens V.","first_name":"Jens V.","last_name":"Stein"},{"first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-4561-241X","full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87"}],"date_created":"2021-08-06T09:09:11Z","month":"07","status":"public","intvolume":"        23","isi":1,"file_date_updated":"2022-07-25T07:11:32Z","article_type":"original","publisher":"Springer Nature","volume":23,"acknowledgement":"This research was supported by the Scientific Service Units of IST Austria through resources provided by the Imaging and Optics, Electron Microscopy, Preclinical and Life Science Facilities. We thank C. Moussion for providing anti-PNAd antibody and D. Critchley for Talin1-floxed mice, and E. Papusheva for providing a custom 3D channel alignment script. This work was supported by a European Research Council grant ERC-CoG-72437 to M.S. M.H. was supported by Czech Sciencundation GACR 20-24603Y and Charles University PRIMUS/20/MED/013.","acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"},{"_id":"LifeSc"}],"ec_funded":1,"language":[{"iso":"eng"}],"doi":"10.1038/s41590-022-01257-4","has_accepted_license":"1","department":[{"_id":"SiHi"},{"_id":"CaHe"},{"_id":"EdHa"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"MiSi"}],"date_updated":"2023-08-02T06:53:07Z","type":"journal_article","oa_version":"Published Version","day":"11","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","publication_identifier":{"issn":["1529-2908"],"eissn":["1529-2916"]},"scopus_import":"1","date_published":"2022-07-11T00:00:00Z","external_id":{"isi":["000822975900002"]},"file":[{"date_created":"2022-07-25T07:11:32Z","relation":"main_file","file_size":11475325,"content_type":"application/pdf","creator":"dernst","file_id":"11642","date_updated":"2022-07-25T07:11:32Z","success":1,"access_level":"open_access","file_name":"2022_NatureImmunology_Assen.pdf","checksum":"628e7b49809f22c75b428842efe70c68"}],"page":"1246-1255"},{"scopus_import":"1","publication_identifier":{"eissn":["2050084X"]},"file":[{"access_level":"open_access","checksum":"cc1b9bf866d0f61f965556e0dd03d3ac","file_name":"2022_eLife_Valperga.pdf","file_id":"10830","date_updated":"2022-03-07T07:39:25Z","success":1,"content_type":"application/pdf","creator":"dernst","file_size":4095591,"date_created":"2022-03-07T07:39:25Z","relation":"main_file"}],"external_id":{"isi":["000763432300001"],"pmid":["35201977"]},"date_published":"2022-02-24T00:00:00Z","department":[{"_id":"MaDe"}],"has_accepted_license":"1","doi":"10.7554/eLife.68040","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"ScienComp"}],"acknowledgement":"We would like to thank Gemma Chandratillake and Merav Cohen for identifying mutants and José David Moñino Sánchez for his help on neurosecretion assays. We are grateful to Kaveh Ashrafi (UCSF), Piali Sengupta (Brandeis), and the Caenorhabditis Genetic Center (funded by National Institutes of Health Infrastructure Program P40 OD010440) for strains and reagents ... and Rebecca Butcher (Univ. Florida) for C9 pheromone. We thank Tim Stevens, Paula Freire-Pritchett, Alastair Crisp, GurpreetGhattaoraya, and Fabian Amman for help with bioinformatic analysis, Ekaterina Lashmanova for help with injections, Iris Hardege for strains, and Isabel Beets (KU Leuven) and members of the de Bono Lab for comments on the manuscript. We thank the CRUK Cambridge Research Institute Genomics Core for next generation sequencing and the Flow Cytometry Facility at LMB for FACS. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF), the Life Science Facility (LSF) and Scientific Computing (SciCo-p– Bioinformatics).\r\nThis work was supported by the Medical Research Council UK (Studentship to GV), an\r\nAdvanced ERC grant (269,058 ACMO to MdB), and a Wellcome Investigator Award (209504/Z/17/Z to MdB).","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","day":"24","oa_version":"Published Version","type":"journal_article","date_updated":"2023-08-02T14:42:55Z","isi":1,"intvolume":"        11","article_number":"e68040","status":"public","month":"02","date_created":"2022-03-06T23:01:52Z","volume":11,"article_type":"original","publisher":"eLife Sciences Publications","file_date_updated":"2022-03-07T07:39:25Z","_id":"10826","ddc":["570"],"oa":1,"pmid":1,"publication":"eLife","title":"Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in Caenorhabditis elegans","abstract":[{"text":"Animals that lose one sensory modality often show augmented responses to other sensory inputs. The mechanisms underpinning this cross-modal plasticity are poorly understood. We probe such mechanisms by performing a forward genetic screen for mutants with enhanced O2 perception in Caenorhabditis elegans. Multiple mutants exhibiting increased O2 responsiveness concomitantly show defects in other sensory responses. One mutant, qui-1, defective in a conserved NACHT/WD40 protein, abolishes pheromone-evoked Ca2+ responses in the ADL pheromone-sensing neurons. At the same time, ADL responsiveness to pre-synaptic input from O2-sensing neurons is heightened in qui-1, and other sensory defective mutants, resulting in enhanced neurosecretion although not increased Ca2+ responses. Expressing qui-1 selectively in ADL rescues both the qui-1 ADL neurosecretory phenotype and enhanced escape from 21% O2. Profiling ADL neurons in qui-1 mutants highlights extensive changes in gene expression, notably of many neuropeptide receptors. We show that elevated ADL expression of the conserved neuropeptide receptor NPR-22 is necessary for enhanced ADL neurosecretion in qui-1 mutants, and is sufficient to confer increased ADL neurosecretion in control animals. Sensory loss can thus confer cross-modal plasticity by changing the peptidergic connectome.","lang":"eng"}],"publication_status":"published","project":[{"_id":"23870BE8-32DE-11EA-91FC-C7463DDC885E","grant_number":"209504/A/17/Z","name":"Molecular mechanisms of neural circuit function"}],"quality_controlled":"1","author":[{"full_name":"Valperga, Giulio","id":"67F289DE-0D8F-11EA-9BDD-54AE3DDC885E","last_name":"Valperga","first_name":"Giulio"},{"id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8347-0443","full_name":"De Bono, Mario","last_name":"De Bono","first_name":"Mario"}],"citation":{"ama":"Valperga G, de Bono M. Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in Caenorhabditis elegans. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.68040\">10.7554/eLife.68040</a>","ieee":"G. Valperga and M. de Bono, “Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in Caenorhabditis elegans,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","ista":"Valperga G, de Bono M. 2022. Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in Caenorhabditis elegans. eLife. 11, e68040.","chicago":"Valperga, Giulio, and Mario de Bono. “Impairing One Sensory Modality Enhances Another by Reconfiguring Peptidergic Signalling in Caenorhabditis Elegans.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.68040\">https://doi.org/10.7554/eLife.68040</a>.","short":"G. Valperga, M. de Bono, ELife 11 (2022).","apa":"Valperga, G., &#38; de Bono, M. (2022). Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in Caenorhabditis elegans. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.68040\">https://doi.org/10.7554/eLife.68040</a>","mla":"Valperga, Giulio, and Mario de Bono. “Impairing One Sensory Modality Enhances Another by Reconfiguring Peptidergic Signalling in Caenorhabditis Elegans.” <i>ELife</i>, vol. 11, e68040, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.68040\">10.7554/eLife.68040</a>."},"year":"2022","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"}},{"ddc":["572"],"oa":1,"related_material":{"record":[{"relation":"used_in_publication","status":"public","id":"11373"},{"id":"14280","status":"public","relation":"used_in_publication"}],"link":[{"description":"A custom written code (FRAPdiff) to quantify the Off binding rate and Diffusion coefficient of membrane bound proteins. Written by Christoph Sommer.","relation":"software","url":"https://doi.org/10.5281/zenodo.6400639"}]},"_id":"10934","title":"In vitro reconstitution of Escherichia coli divisome activation","abstract":[{"text":"FtsA is crucial for assembly of the E. coli divisome, as it dynamically links cytoplasmic FtsZ filaments with transmembrane cell division proteins. FtsA allegedly initiates cell division by switching from an inactive polymeric to an active monomeric confirmation, which recruits downstream proteins and stabilizes FtsZ filaments. Here, we use biochemical reconstitution experiments combined with quantitative fluorescence microscopy to study divisome activation in vitro. We compare wildtype-FtsA with FtsA-R286W, a constantly active gain-of-function mutant and find that R286W outperforms the wildtype protein in replicating FtsZ treadmilling dynamics, stabilizing FtsZ filaments and recruiting FtsN. We attribute these differences to a faster membrane exchange of FtsA-R286W and its higher packing density below FtsZ filaments.  Using FRET microscopy, we find that FtsN binding does not compete with, but promotes FtsA self-interaction. Our findings suggest a model where FtsA always forms dynamic polymers on the membrane, which re-organize during assembly and activation of the divisome. ","lang":"eng"}],"project":[{"name":"Self-Organization of the Bacterial Cell","grant_number":"679239","_id":"2595697A-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"_id":"fc38323b-9c52-11eb-aca3-ff8afb4a011d","name":"Understanding bacterial cell division by in vitro\r\nreconstitution","grant_number":"P34607"}],"author":[{"last_name":"Radler","first_name":"Philipp","orcid":" 0000-0001-9198-2182 ","full_name":"Radler, Philipp","id":"40136C2A-F248-11E8-B48F-1D18A9856A87"}],"citation":{"ieee":"P. Radler, “In vitro reconstitution of Escherichia coli divisome activation.” Institute of Science and Technology Austria, 2022.","ama":"Radler P. In vitro reconstitution of Escherichia coli divisome activation. 2022. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:10934\">10.15479/AT:ISTA:10934</a>","chicago":"Radler, Philipp. “In Vitro Reconstitution of Escherichia Coli Divisome Activation.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/AT:ISTA:10934\">https://doi.org/10.15479/AT:ISTA:10934</a>.","short":"P. Radler, (2022).","ista":"Radler P. 2022. In vitro reconstitution of Escherichia coli divisome activation, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:10934\">10.15479/AT:ISTA:10934</a>.","mla":"Radler, Philipp. <i>In Vitro Reconstitution of Escherichia Coli Divisome Activation</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:10934\">10.15479/AT:ISTA:10934</a>.","apa":"Radler, P. (2022). In vitro reconstitution of Escherichia coli divisome activation. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:10934\">https://doi.org/10.15479/AT:ISTA:10934</a>"},"year":"2022","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"status":"public","date_created":"2022-03-31T11:32:32Z","month":"04","publisher":"Institute of Science and Technology Austria","file_date_updated":"2022-04-22T10:15:19Z","doi":"10.15479/AT:ISTA:10934","has_accepted_license":"1","department":[{"_id":"GradSch"},{"_id":"MaLo"}],"ec_funded":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"acknowledgement":"We acknowledge members of the Loose laboratory at IST Austria for helpful discussions—in particular L. Lindorfer for his assistance with cloning and purifications. We thank J. Löwe and T. Nierhaus (MRC-LMB Cambridge, UK) for sharing unpublished work and helpful discussions, as well as D. Vavylonis and D. Rutkowski (Lehigh University, Bethlehem, PA, USA) as well as S. Martin (University of Lausanne, Switzerland) for sharing their code for FRAP analysis. We are also thankful for the support by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging and Optics Facility (IOF) and the Lab Support Facility (LSF). This work was supported by the European Research Council through grant ERC 2015-StG-679239 and by the Austrian Science Fund (FWF) StandAlone P34607 to M.L. and HFSP LT 000824/2016-L4 to N.B. 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This research was also supported by the Scientific Service Units (SSUs) of IST Austria through resources provided by Scientific Computing (SciComp), the Life Science Facility (LSF), and the Electron Microscopy Facility (EMF). We thank Dustin Morado for providing the software SubTOM for data processing. We also thank William Wan for critical reading of the manuscript and valuable feedback.","language":[{"iso":"eng"}],"doi":"10.1016/j.jsb.2022.107852","has_accepted_license":"1","department":[{"_id":"FlSc"}],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"ScienComp"},{"_id":"EM-Fac"}],"day":"01","type":"journal_article","date_updated":"2023-08-03T06:25:23Z","oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"Yes (via OA deal)","status":"public","article_number":"107852","date_created":"2022-04-15T07:10:26Z","month":"06","isi":1,"intvolume":"       214","publisher":"Elsevier","article_type":"original","file_date_updated":"2022-08-02T11:07:58Z","volume":214,"issue":"2","publication_status":"published","abstract":[{"text":"The potential of energy filtering and direct electron detection for cryo-electron microscopy (cryo-EM) has been well documented. Here, we assess the performance of recently introduced hardware for cryo-electron tomography (cryo-ET) and subtomogram averaging (STA), an increasingly popular structural determination method for complex 3D specimens. We acquired cryo-ET datasets of EIAV virus-like particles (VLPs) on two contemporary cryo-EM systems equipped with different energy filters and direct electron detectors (DED), specifically a Krios G4, equipped with a cold field emission gun (CFEG), Thermo Fisher Scientific Selectris X energy filter, and a Falcon 4 DED; and a Krios G3i, with a Schottky field emission gun (XFEG), a Gatan Bioquantum energy filter, and a K3 DED. We performed constrained cross-correlation-based STA on equally sized datasets acquired on the respective systems. The resulting EIAV CA hexamer reconstructions show that both systems perform comparably in the 4–6 Å resolution range based on Fourier-Shell correlation (FSC). In addition, by employing a recently introduced multiparticle refinement approach, we obtained a reconstruction of the EIAV CA hexamer at 2.9 Å. Our results demonstrate the potential of the new generation of energy filters and DEDs for STA, and the effects of using different processing pipelines on their STA outcomes.","lang":"eng"}],"project":[{"name":"Structural conservation and diversity in retroviral capsid","grant_number":"P31445","_id":"26736D6A-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"ddc":["570"],"oa":1,"_id":"11155","publication":"Journal of Structural Biology","title":"Exploring high-resolution cryo-ET and subtomogram averaging capabilities of contemporary DEDs","pmid":1,"year":"2022","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"quality_controlled":"1","author":[{"id":"4741CA5A-F248-11E8-B48F-1D18A9856A87","full_name":"Obr, Martin","first_name":"Martin","last_name":"Obr"},{"full_name":"Hagen, Wim J.H.","last_name":"Hagen","first_name":"Wim J.H."},{"last_name":"Dick","first_name":"Robert A.","full_name":"Dick, Robert A."},{"first_name":"Lingbo","last_name":"Yu","full_name":"Yu, Lingbo"},{"first_name":"Abhay","last_name":"Kotecha","full_name":"Kotecha, Abhay"},{"first_name":"Florian KM","last_name":"Schur","full_name":"Schur, Florian KM","orcid":"0000-0003-4790-8078","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"}],"citation":{"mla":"Obr, Martin, et al. “Exploring High-Resolution Cryo-ET and Subtomogram Averaging Capabilities of Contemporary DEDs.” <i>Journal of Structural Biology</i>, vol. 214, no. 2, 107852, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.jsb.2022.107852\">10.1016/j.jsb.2022.107852</a>.","apa":"Obr, M., Hagen, W. J. H., Dick, R. A., Yu, L., Kotecha, A., &#38; Schur, F. K. (2022). Exploring high-resolution cryo-ET and subtomogram averaging capabilities of contemporary DEDs. <i>Journal of Structural Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jsb.2022.107852\">https://doi.org/10.1016/j.jsb.2022.107852</a>","ista":"Obr M, Hagen WJH, Dick RA, Yu L, Kotecha A, Schur FK. 2022. Exploring high-resolution cryo-ET and subtomogram averaging capabilities of contemporary DEDs. Journal of Structural Biology. 214(2), 107852.","chicago":"Obr, Martin, Wim J.H. Hagen, Robert A. Dick, Lingbo Yu, Abhay Kotecha, and Florian KM Schur. “Exploring High-Resolution Cryo-ET and Subtomogram Averaging Capabilities of Contemporary DEDs.” <i>Journal of Structural Biology</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.jsb.2022.107852\">https://doi.org/10.1016/j.jsb.2022.107852</a>.","short":"M. Obr, W.J.H. Hagen, R.A. Dick, L. Yu, A. Kotecha, F.K. Schur, Journal of Structural Biology 214 (2022).","ama":"Obr M, Hagen WJH, Dick RA, Yu L, Kotecha A, Schur FK. Exploring high-resolution cryo-ET and subtomogram averaging capabilities of contemporary DEDs. <i>Journal of Structural Biology</i>. 2022;214(2). doi:<a href=\"https://doi.org/10.1016/j.jsb.2022.107852\">10.1016/j.jsb.2022.107852</a>","ieee":"M. Obr, W. J. H. Hagen, R. A. Dick, L. Yu, A. Kotecha, and F. K. Schur, “Exploring high-resolution cryo-ET and subtomogram averaging capabilities of contemporary DEDs,” <i>Journal of Structural Biology</i>, vol. 214, no. 2. Elsevier, 2022."}},{"status":"public","article_number":"110615","month":"04","date_created":"2022-04-15T09:03:10Z","isi":1,"intvolume":"        39","article_type":"original","publisher":"Elsevier","file_date_updated":"2022-04-15T09:06:25Z","issue":"1","volume":39,"abstract":[{"text":"Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling.","lang":"eng"}],"publication_status":"published","project":[{"_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"grant_number":"I04205","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","_id":"2690FEAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"_id":"11160","ddc":["570"],"related_material":{"record":[{"id":"12364","relation":"dissertation_contains","status":"public"}]},"oa":1,"pmid":1,"publication":"Cell Reports","title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","year":"2022","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"author":[{"full_name":"Villa, Carlo Emanuele","last_name":"Villa","first_name":"Carlo Emanuele"},{"full_name":"Cheroni, Cristina","first_name":"Cristina","last_name":"Cheroni"},{"last_name":"Dotter","first_name":"Christoph","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"López-Tóbon, Alejandro","last_name":"López-Tóbon","first_name":"Alejandro"},{"id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara","last_name":"Oliveira","first_name":"Bárbara"},{"id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","full_name":"Sacco, Roberto","first_name":"Roberto","last_name":"Sacco"},{"last_name":"Yahya","first_name":"Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","full_name":"Yahya, Aysan Çerağ"},{"first_name":"Jasmin","last_name":"Morandell","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Gabriele, Michele","first_name":"Michele","last_name":"Gabriele"},{"last_name":"Tavakoli","first_name":"Mojtaba","orcid":"0000-0002-7667-6854","full_name":"Tavakoli, Mojtaba","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Julia","last_name":"Lyudchik","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","last_name":"Sommer"},{"full_name":"Gabitto, Mariano","last_name":"Gabitto","first_name":"Mariano"},{"last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Giuseppe","last_name":"Testa","full_name":"Testa, Giuseppe"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia"}],"quality_controlled":"1","citation":{"ieee":"C. E. Villa <i>et al.</i>, “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” <i>Cell Reports</i>, vol. 39, no. 1. Elsevier, 2022.","ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. 2022;39(1). doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>","short":"C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).","chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>.","ista":"Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.","mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>, vol. 39, no. 1, 110615, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>.","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>"},"publication_identifier":{"issn":["2211-1247"]},"keyword":["General Biochemistry","Genetics and Molecular Biology"],"file":[{"file_size":"7808644","content_type":"application/pdf","creator":"dernst","relation":"main_file","date_created":"2022-04-15T09:06:25Z","checksum":"b4e8d68f0268dec499af333e6fd5d8e1","file_name":"2022_CellReports_Villa.pdf","access_level":"open_access","success":1,"date_updated":"2022-04-15T09:06:25Z","file_id":"11164"}],"external_id":{"pmid":["35385734"],"isi":["000785983900003"]},"date_published":"2022-04-05T00:00:00Z","acknowledgement":"We thank Farnaz Freeman for technical assistance. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This work supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs); the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele; and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures were created using BioRender.com.","has_accepted_license":"1","department":[{"_id":"JoDa"},{"_id":"GaNo"}],"language":[{"iso":"eng"}],"doi":"10.1016/j.celrep.2022.110615","ec_funded":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"day":"05","oa_version":"Published Version","date_updated":"2024-03-25T23:30:25Z","type":"journal_article","article_processing_charge":"Yes","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87"},{"author":[{"last_name":"Wachner","first_name":"Stephanie","id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87","full_name":"Wachner, Stephanie"}],"citation":{"apa":"Wachner, S. (2022). <i>Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11193\">https://doi.org/10.15479/at:ista:11193</a>","mla":"Wachner, Stephanie. <i>Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11193\">10.15479/at:ista:11193</a>.","ista":"Wachner S. 2022. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. Institute of Science and Technology Austria.","short":"S. Wachner, Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells, Institute of Science and Technology Austria, 2022.","chicago":"Wachner, Stephanie. “Transcriptional Regulation by Dfos and BMP-Signaling Support Tissue Invasion of Drosophila Immune Cells.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11193\">https://doi.org/10.15479/at:ista:11193</a>.","ieee":"S. Wachner, “Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells,” Institute of Science and Technology Austria, 2022.","ama":"Wachner S. Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11193\">10.15479/at:ista:11193</a>"},"year":"2022","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"_id":"11193","oa":1,"ddc":["570"],"related_material":{"record":[{"id":"10614","relation":"part_of_dissertation","status":"public"},{"status":"public","relation":"part_of_dissertation","id":"544"}]},"title":"Transcriptional regulation by Dfos and BMP-signaling support tissue invasion of Drosophila immune cells","abstract":[{"lang":"eng","text":"The infiltration of immune cells into tissues underlies the establishment of tissue-resident\r\nmacrophages and responses to infections and tumors. However, the mechanisms immune\r\ncells utilize to collectively migrate through tissue barriers in vivo are not yet well understood.\r\nIn this thesis, I describe two mechanisms that Drosophila immune cells (hemocytes) use to\r\novercome the tissue barrier of the germband in the embryo. One strategy is the strengthening\r\nof the actin cortex through developmentally controlled transcriptional regulation induced by\r\nthe Drosophila proto-oncogene family member Dfos, which I show in Chapter 2. Dfos induces\r\nexpression of the tetraspanin TM4SF and the filamin Cher leading to higher levels of the\r\nactivated formin Dia at the cortex and increased cortical F-actin. This enhanced cortical\r\nstrength allows hemocytes to overcome the physical resistance of the surrounding tissue and\r\ntranslocate their nucleus to move forward. This mechanism affects the speed of migration\r\nwhen hemocytes face a confined environment in vivo.\r\nAnother aspect of the invasion process is the initial step of the leading hemocytes entering\r\nthe tissue, which potentially guides the follower cells. In Chapter 3, I describe a novel\r\nsubpopulation of hemocytes activated by BMP signaling prior to tissue invasion that leads\r\npenetration into the germband. Hemocytes that are deficient in BMP signaling activation\r\nshow impaired persistence at the tissue entry, while their migration speed remains\r\nunaffected.\r\nThis suggests that there might be different mechanisms controlling immune cell migration\r\nwithin the confined environment in vivo, one of these being the general ability to overcome\r\nthe resistance of the surrounding tissue and another affecting the order of hemocytes that\r\ncollectively invade the tissue in a stream of individual cells.\r\nTogether, my findings provide deeper insights into transcriptional changes in immune\r\ncells that enable efficient tissue invasion and pave the way for future studies investigating the\r\nearly colonization of tissues by macrophages in higher organisms. Moreover, they extend the\r\ncurrent view of Drosophila immune cell heterogeneity and point toward a potentially\r\nconserved role for canonical BMP signaling in specifying immune cells that lead the migration\r\nof tissue resident macrophages during embryogenesis."}],"publication_status":"published","project":[{"_id":"26199CA4-B435-11E9-9278-68D0E5697425","name":"Tissue barrier penetration is crucial for immunity and metastasis","grant_number":"24800"}],"publisher":"Institute of Science and Technology Austria","file_date_updated":"2023-04-21T22:30:03Z","degree_awarded":"PhD","status":"public","month":"04","date_created":"2022-04-20T08:59:07Z","article_processing_charge":"No","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","supervisor":[{"full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","last_name":"Siekhaus","first_name":"Daria E"}],"day":"20","oa_version":"Published Version","date_updated":"2023-09-19T10:15:54Z","type":"dissertation","has_accepted_license":"1","department":[{"_id":"GradSch"},{"_id":"DaSi"}],"language":[{"iso":"eng"}],"doi":"10.15479/at:ista:11193","acknowledged_ssus":[{"_id":"LifeSc"}],"page":"170","file":[{"date_updated":"2023-04-21T22:30:03Z","file_id":"11195","checksum":"999ab16884c4522486136ebc5ae8dbff","file_name":"Thesis_Stephanie_Wachner_20200414_formatted.pdf","access_level":"open_access","relation":"main_file","date_created":"2022-04-20T09:03:57Z","content_type":"application/pdf","creator":"cchlebak","file_size":8820951,"embargo":"2023-04-20"},{"content_type":"application/x-zip-compressed","creator":"cchlebak","file_size":65864612,"embargo_to":"open_access","relation":"source_file","date_created":"2022-04-22T12:41:00Z","file_name":"Thesis_Stephanie_Wachner_20200414.zip","checksum":"fd92b1e38d53bdf8b458213882d41383","access_level":"closed","date_updated":"2023-04-21T22:30:03Z","file_id":"11329"}],"date_published":"2022-04-20T00:00:00Z","publication_identifier":{"issn":["2663-337X"]},"alternative_title":["ISTA Thesis"]},{"tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"year":"2022","citation":{"mla":"Amberg, Nicole, et al. “Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.” <i>Science Advances</i>, vol. 8, no. 44, abq1263, American Association for the Advancement of Science, 2022, doi:<a href=\"https://doi.org/10.1126/sciadv.abq1263\">10.1126/sciadv.abq1263</a>.","apa":"Amberg, N., Pauler, F., Streicher, C., &#38; Hippenmeyer, S. (2022). Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. <i>Science Advances</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciadv.abq1263\">https://doi.org/10.1126/sciadv.abq1263</a>","chicago":"Amberg, Nicole, Florian Pauler, Carmen Streicher, and Simon Hippenmeyer. “Tissue-Wide Genetic and Cellular Landscape Shapes the Execution of Sequential PRC2 Functions in Neural Stem Cell Lineage Progression.” <i>Science Advances</i>. American Association for the Advancement of Science, 2022. <a href=\"https://doi.org/10.1126/sciadv.abq1263\">https://doi.org/10.1126/sciadv.abq1263</a>.","short":"N. Amberg, F. Pauler, C. Streicher, S. Hippenmeyer, Science Advances 8 (2022).","ista":"Amberg N, Pauler F, Streicher C, Hippenmeyer S. 2022. Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. Science Advances. 8(44), abq1263.","ieee":"N. Amberg, F. Pauler, C. Streicher, and S. Hippenmeyer, “Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression,” <i>Science Advances</i>, vol. 8, no. 44. American Association for the Advancement of Science, 2022.","ama":"Amberg N, Pauler F, Streicher C, Hippenmeyer S. Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression. <i>Science Advances</i>. 2022;8(44). doi:<a href=\"https://doi.org/10.1126/sciadv.abq1263\">10.1126/sciadv.abq1263</a>"},"author":[{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","first_name":"Nicole","last_name":"Amberg"},{"first_name":"Florian","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","last_name":"Streicher","first_name":"Carmen"},{"first_name":"Simon","last_name":"Hippenmeyer","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"}],"quality_controlled":"1","project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"},{"grant_number":"T0101031","name":"Role of Eed in neural stem cell lineage progression","_id":"268F8446-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"publication_status":"published","abstract":[{"lang":"eng","text":"The generation of a correctly-sized cerebral cortex with all-embracing neuronal and glial cell-type diversity critically depends on faithful radial glial progenitor (RGP) cell proliferation/differentiation programs. Temporal RGP lineage progression is regulated by Polycomb Repressive Complex 2 (PRC2) and loss of PRC2 activity results in severe neurogenesis defects and microcephaly. How PRC2-dependent gene expression instructs RGP lineage progression is unknown. Here we utilize Mosaic Analysis with Double Markers (MADM)-based single cell technology and demonstrate that PRC2 is not cell-autonomously required in neurogenic RGPs but rather acts at the global tissue-wide level. Conversely, cortical astrocyte production and maturation is cell-autonomously controlled by PRC2-dependent transcriptional regulation. We thus reveal highly distinct and sequential PRC2 functions in RGP lineage progression that are dependent on complex interplays between intrinsic and tissue-wide properties. In a broader context our results imply a critical role for the genetic and cellular niche environment in neural stem cell behavior."}],"title":"Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression","publication":"Science Advances","ddc":["570"],"related_material":{"link":[{"relation":"press_release","url":"https://ista.ac.at/en/news/whole-tissue-shapes-brain-development/","description":"News on ISTA website"}]},"oa":1,"_id":"11336","file_date_updated":"2023-03-21T14:18:10Z","article_type":"original","publisher":"American Association for the Advancement of Science","issue":"44","volume":8,"date_created":"2022-04-26T15:04:50Z","month":"11","status":"public","article_number":"abq1263","intvolume":"         8","type":"journal_article","date_updated":"2023-05-31T12:24:10Z","oa_version":"Published Version","day":"01","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","acknowledgement":"We thank A. Heger (IST Austria Preclinical Facility), A. Sommer and C. Czepe (VBCF GmbH, NGS  Unit)  and  S.  Gharagozlou  for  technical  support.  This  research  was  supported  by  the  Scientific  Service  Units  (SSU)  of  IST  Austria  through  resources  provided  by  the  Imaging  &  Optics Facility (IOF), Lab Support Facility (LSF), and Preclinical Facility (PCF). N.A. received funding   from   the   FWF   Firnberg-Programm   (T   1031).   The   work   was   supported   by   IST   institutional  funds  and  by  the  European  Research  Council  (ERC)  under  the  European  Union’s  Horizon 2020 research and innovation program (grant agreement 725780 LinPro) to S.H.","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"}],"ec_funded":1,"language":[{"iso":"eng"}],"doi":"10.1126/sciadv.abq1263","department":[{"_id":"SiHi"}],"has_accepted_license":"1","date_published":"2022-11-01T00:00:00Z","file":[{"relation":"main_file","date_created":"2023-03-21T14:18:10Z","creator":"patrickd","content_type":"application/pdf","file_size":2973998,"success":1,"file_id":"12742","date_updated":"2023-03-21T14:18:10Z","checksum":"0117023e188542082ca6693cf39e7f03","file_name":"sciadv.abq1263.pdf","access_level":"open_access"}],"publication_identifier":{"issn":["2375-2548"]},"scopus_import":"1"},{"citation":{"ama":"Lukacisin M, Espinosa-Cantú A, Bollenbach MT. Intron-mediated induction of phenotypic heterogeneity. <i>Nature</i>. 2022;605:113-118. doi:<a href=\"https://doi.org/10.1038/s41586-022-04633-0\">10.1038/s41586-022-04633-0</a>","ieee":"M. Lukacisin, A. Espinosa-Cantú, and M. T. Bollenbach, “Intron-mediated induction of phenotypic heterogeneity,” <i>Nature</i>, vol. 605. Springer Nature, pp. 113–118, 2022.","ista":"Lukacisin M, Espinosa-Cantú A, Bollenbach MT. 2022. Intron-mediated induction of phenotypic heterogeneity. Nature. 605, 113–118.","short":"M. Lukacisin, A. Espinosa-Cantú, M.T. Bollenbach, Nature 605 (2022) 113–118.","chicago":"Lukacisin, Martin, Adriana Espinosa-Cantú, and Mark Tobias Bollenbach. “Intron-Mediated Induction of Phenotypic Heterogeneity.” <i>Nature</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41586-022-04633-0\">https://doi.org/10.1038/s41586-022-04633-0</a>.","apa":"Lukacisin, M., Espinosa-Cantú, A., &#38; Bollenbach, M. T. (2022). Intron-mediated induction of phenotypic heterogeneity. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-022-04633-0\">https://doi.org/10.1038/s41586-022-04633-0</a>","mla":"Lukacisin, Martin, et al. “Intron-Mediated Induction of Phenotypic Heterogeneity.” <i>Nature</i>, vol. 605, Springer Nature, 2022, pp. 113–18, doi:<a href=\"https://doi.org/10.1038/s41586-022-04633-0\">10.1038/s41586-022-04633-0</a>."},"author":[{"orcid":"0000-0001-6549-4177","full_name":"Lukacisin, Martin","id":"298FFE8C-F248-11E8-B48F-1D18A9856A87","first_name":"Martin","last_name":"Lukacisin"},{"full_name":"Espinosa-Cantú, Adriana","last_name":"Espinosa-Cantú","first_name":"Adriana"},{"full_name":"Bollenbach, Mark Tobias","orcid":"0000-0003-4398-476X","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","first_name":"Mark Tobias","last_name":"Bollenbach"}],"quality_controlled":"1","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"year":"2022","publication":"Nature","title":"Intron-mediated induction of phenotypic heterogeneity","pmid":1,"ddc":["570"],"oa":1,"_id":"11341","project":[{"name":"Optimality principles in responses to antibiotics","grant_number":"303507","_id":"25E83C2C-B435-11E9-9278-68D0E5697425","call_identifier":"FP7"},{"call_identifier":"FWF","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","name":"Revealing the mechanisms underlying drug interactions","grant_number":"P27201-B22"}],"publication_status":"published","abstract":[{"text":"Intragenic regions that are removed during maturation of the RNA transcript—introns—are universally present in the nuclear genomes of eukaryotes1. The budding yeast, an otherwise intron-poor species, preserves two sets of ribosomal protein genes that differ primarily in their introns2,3. Although studies have shed light on the role of ribosomal protein introns under stress and starvation4,5,6, understanding the contribution of introns to ribosome regulation remains challenging. Here, by combining isogrowth profiling7 with single-cell protein measurements8, we show that introns can mediate inducible phenotypic heterogeneity that confers a clear fitness advantage. Osmotic stress leads to bimodal expression of the small ribosomal subunit protein Rps22B, which is mediated by an intron in the 5′ untranslated region of its transcript. The two resulting yeast subpopulations differ in their ability to cope with starvation. Low levels of Rps22B protein result in prolonged survival under sustained starvation, whereas high levels of Rps22B enable cells to grow faster after transient starvation. Furthermore, yeasts growing at high concentrations of sugar, similar to those in ripe grapes, exhibit bimodal expression of Rps22B when approaching the stationary phase. Differential intron-mediated regulation of ribosomal protein genes thus provides a way to diversify the population when starvation threatens in natural environments. Our findings reveal a role for introns in inducing phenotypic heterogeneity in changing environments, and suggest that duplicated ribosomal protein genes in yeast contribute to resolving the evolutionary conflict between precise expression control and environmental responsiveness9.","lang":"eng"}],"volume":605,"file_date_updated":"2022-08-05T06:08:24Z","publisher":"Springer Nature","article_type":"original","intvolume":"       605","isi":1,"date_created":"2022-05-01T22:01:42Z","month":"05","status":"public","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_updated":"2023-08-03T06:44:50Z","type":"journal_article","oa_version":"Published Version","day":"05","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"Bio"}],"ec_funded":1,"doi":"10.1038/s41586-022-04633-0","language":[{"iso":"eng"}],"has_accepted_license":"1","acknowledgement":"We thank the IST Austria Life Science Facility, the Miba Machine Shop and M. Lukačišinová for support with the liquid handling robot; the Bioimaging Facility at IST Austria, J. Power and B. Meier at the University of Cologne, and C. Göttlinger at the FACS Analysis Facility at the Institute for Genetics, University of Cologne, for support with flow cytometry experiments; L. Horst for the development of the automated experimental methods in Cologne; J. Parenteau, S. Abou Elela, G. Stormo, M. Springer and M. Schuldiner for providing us with yeast strains; B. Fernando, T. Fink, G. Ansmann and G. Chevreau for technical support; H. Köver, G. Tkačik, N. Barton, A. Angermayr and B. Kavčič for support during laboratory relocation; D. Siekhaus, M. Springer and all the members of the Bollenbach group for support and discussions; and K. Mitosch, M. Lukačišinová, G. Liti and A. de Luna for critical reading of our manuscript. This work was supported in part by an Austrian Science Fund (FWF) standalone grant P 27201-B22 (to T.B.), HFSP program Grant RGP0042/2013 (to T.B.), EU Marie Curie Career Integration Grant No. 303507, and German Research Foundation (DFG) Collaborative Research Centre (SFB) 1310 (to T.B.). A.E.-C. was supported by a Georg Forster fellowship from the Alexander von Humboldt Foundation.","date_published":"2022-05-05T00:00:00Z","external_id":{"isi":["000784934100003"],"pmid":["35444278"]},"file":[{"creator":"dernst","content_type":"application/pdf","file_size":25360311,"relation":"main_file","date_created":"2022-08-05T06:08:24Z","checksum":"d68cd1596bb9fd819b750fe47c8a138a","file_name":"2022_Nature_Lukacisin.pdf","access_level":"open_access","success":1,"file_id":"11727","date_updated":"2022-08-05T06:08:24Z"}],"page":"113-118","publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"scopus_import":"1"},{"tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"year":"2022","citation":{"mla":"Radler, Philipp, et al. “In Vitro Reconstitution of Escherichia Coli Divisome Activation.” <i>Nature Communications</i>, vol. 13, 2635, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-30301-y\">10.1038/s41467-022-30301-y</a>.","apa":"Radler, P., Baranova, N. S., Dos Santos Caldas, P. R., Sommer, C. M., Lopez Pelegrin, M. D., Michalik, D., &#38; Loose, M. (2022). In vitro reconstitution of Escherichia coli divisome activation. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-30301-y\">https://doi.org/10.1038/s41467-022-30301-y</a>","ieee":"P. Radler <i>et al.</i>, “In vitro reconstitution of Escherichia coli divisome activation,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.","ama":"Radler P, Baranova NS, Dos Santos Caldas PR, et al. In vitro reconstitution of Escherichia coli divisome activation. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-30301-y\">10.1038/s41467-022-30301-y</a>","ista":"Radler P, Baranova NS, Dos Santos Caldas PR, Sommer CM, Lopez Pelegrin MD, Michalik D, Loose M. 2022. In vitro reconstitution of Escherichia coli divisome activation. Nature Communications. 13, 2635.","short":"P. Radler, N.S. Baranova, P.R. Dos Santos Caldas, C.M. Sommer, M.D. Lopez Pelegrin, D. Michalik, M. Loose, Nature Communications 13 (2022).","chicago":"Radler, Philipp, Natalia S. Baranova, Paulo R Dos Santos Caldas, Christoph M Sommer, Maria D Lopez Pelegrin, David Michalik, and Martin Loose. “In Vitro Reconstitution of Escherichia Coli Divisome Activation.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-30301-y\">https://doi.org/10.1038/s41467-022-30301-y</a>."},"author":[{"first_name":"Philipp","last_name":"Radler","id":"40136C2A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9198-2182 ","full_name":"Radler, Philipp"},{"orcid":"0000-0002-3086-9124","full_name":"Baranova, Natalia S.","id":"38661662-F248-11E8-B48F-1D18A9856A87","first_name":"Natalia S.","last_name":"Baranova"},{"orcid":"0000-0001-6730-4461","full_name":"Dos Santos Caldas, Paulo R","id":"38FCDB4C-F248-11E8-B48F-1D18A9856A87","first_name":"Paulo R","last_name":"Dos Santos Caldas"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer","first_name":"Christoph M"},{"last_name":"Lopez Pelegrin","first_name":"Maria D","id":"319AA9CE-F248-11E8-B48F-1D18A9856A87","full_name":"Lopez Pelegrin, Maria D"},{"full_name":"Michalik, David","id":"B9577E20-AA38-11E9-AC9A-0930E6697425","first_name":"David","last_name":"Michalik"},{"last_name":"Loose","first_name":"Martin","id":"462D4284-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7309-9724","full_name":"Loose, Martin"}],"quality_controlled":"1","project":[{"grant_number":"679239","name":"Self-Organization of the Bacterial Cell","call_identifier":"H2020","_id":"2595697A-B435-11E9-9278-68D0E5697425"},{"grant_number":"P34607","name":"Understanding bacterial cell division by in vitro\r\nreconstitution","_id":"fc38323b-9c52-11eb-aca3-ff8afb4a011d"}],"abstract":[{"lang":"eng","text":"The actin-homologue FtsA is essential for E. coli cell division, as it links FtsZ filaments in the Z-ring to transmembrane proteins. FtsA is thought to initiate cell constriction by switching from an inactive polymeric to an active monomeric conformation, which recruits downstream proteins and stabilizes the Z-ring. However, direct biochemical evidence for this mechanism is missing. Here, we use reconstitution experiments and quantitative fluorescence microscopy to study divisome activation in vitro. By comparing wild-type FtsA with FtsA R286W, we find that this hyperactive mutant outperforms FtsA WT in replicating FtsZ treadmilling dynamics, FtsZ filament stabilization and recruitment of FtsN. We could attribute these differences to a faster exchange and denser packing of FtsA R286W below FtsZ filaments. Using FRET microscopy, we also find that FtsN binding promotes FtsA self-interaction. We propose that in the active divisome FtsA and FtsN exist as a dynamic copolymer that follows treadmilling filaments of FtsZ."}],"publication_status":"published","publication":"Nature Communications","title":"In vitro reconstitution of Escherichia coli divisome activation","_id":"11373","related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1038/s41467-022-34485-1"}],"record":[{"relation":"dissertation_contains","status":"public","id":"14280"},{"id":"10934","relation":"research_data","status":"public"}]},"oa":1,"ddc":["570"],"file_date_updated":"2022-05-13T09:10:51Z","publisher":"Springer Nature","article_type":"original","volume":13,"month":"05","date_created":"2022-05-13T09:06:28Z","article_number":"2635","status":"public","intvolume":"        13","isi":1,"oa_version":"Published Version","date_updated":"2024-02-21T12:35:18Z","type":"journal_article","day":"12","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","acknowledgement":"We acknowledge members of the Loose laboratory at IST Austria for helpful discussions—in particular L. Lindorfer for his assistance with cloning and purifications. We thank J. Löwe and T. Nierhaus (MRC-LMB Cambridge, UK) for sharing unpublished work and helpful discussions, as well as D. Vavylonis and D. Rutkowski (Lehigh University, Bethlehem, PA, USA) and S. Martin (University of Lausanne, Switzerland) for sharing their code for FRAP analysis. We are also thankful for the support by the Scientific Service Units (SSU) of IST Austria through resources provided by the Imaging and Optics Facility (IOF) and the Lab Support Facility (LSF). This work was supported by the European Research Council through grant ERC 2015-StG-679239 and by the Austrian Science Fund (FWF) StandAlone P34607 to M.L. and HFSP LT 000824/2016-L4 to N.B. For the purpose of open access, we have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"ec_funded":1,"department":[{"_id":"MaLo"}],"has_accepted_license":"1","language":[{"iso":"eng"}],"doi":"10.1038/s41467-022-30301-y","file":[{"creator":"dernst","content_type":"application/pdf","file_size":6945191,"date_created":"2022-05-13T09:10:51Z","relation":"main_file","access_level":"open_access","file_name":"2022_NatureCommunications_Radler.pdf","checksum":"5af863ee1b95a0710f6ee864d68dc7a6","date_updated":"2022-05-13T09:10:51Z","file_id":"11374","success":1}],"external_id":{"isi":["000795171100037"]},"keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry"],"date_published":"2022-05-12T00:00:00Z","scopus_import":"1","publication_identifier":{"issn":["2041-1723"]}},{"tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"year":"2022","citation":{"mla":"Gonzalez Somermeyer, Louisa, et al. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” <i>ELife</i>, vol. 11, 75842, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.75842\">10.7554/elife.75842</a>.","apa":"Gonzalez Somermeyer, L., Fleiss, A., Mishin, A. S., Bozhanova, N. G., Igolkina, A. A., Meiler, J., … Kondrashov, F. (2022). Heterogeneity of the GFP fitness landscape and data-driven protein design. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.75842\">https://doi.org/10.7554/elife.75842</a>","ieee":"L. Gonzalez Somermeyer <i>et al.</i>, “Heterogeneity of the GFP fitness landscape and data-driven protein design,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","ama":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, et al. Heterogeneity of the GFP fitness landscape and data-driven protein design. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.75842\">10.7554/elife.75842</a>","short":"L. Gonzalez Somermeyer, A. Fleiss, A.S. Mishin, N.G. Bozhanova, A.A. Igolkina, J. Meiler, M.-E. Alaball Pujol, E.V. Putintseva, K.S. Sarkisyan, F. Kondrashov, ELife 11 (2022).","chicago":"Gonzalez Somermeyer, Louisa, Aubin Fleiss, Alexander S Mishin, Nina G Bozhanova, Anna A Igolkina, Jens Meiler, Maria-Elisenda Alaball Pujol, Ekaterina V Putintseva, Karen S Sarkisyan, and Fyodor Kondrashov. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.75842\">https://doi.org/10.7554/elife.75842</a>.","ista":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, Bozhanova NG, Igolkina AA, Meiler J, Alaball Pujol M-E, Putintseva EV, Sarkisyan KS, Kondrashov F. 2022. Heterogeneity of the GFP fitness landscape and data-driven protein design. eLife. 11, 75842."},"author":[{"first_name":"Louisa","last_name":"Gonzalez Somermeyer","full_name":"Gonzalez Somermeyer, Louisa","orcid":"0000-0001-9139-5383","id":"4720D23C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Fleiss, Aubin","last_name":"Fleiss","first_name":"Aubin"},{"first_name":"Alexander S","last_name":"Mishin","full_name":"Mishin, Alexander S"},{"last_name":"Bozhanova","first_name":"Nina G","full_name":"Bozhanova, Nina G"},{"full_name":"Igolkina, Anna A","last_name":"Igolkina","first_name":"Anna A"},{"first_name":"Jens","last_name":"Meiler","full_name":"Meiler, Jens"},{"full_name":"Alaball Pujol, Maria-Elisenda","last_name":"Alaball Pujol","first_name":"Maria-Elisenda"},{"last_name":"Putintseva","first_name":"Ekaterina V","full_name":"Putintseva, Ekaterina V"},{"last_name":"Sarkisyan","first_name":"Karen S","full_name":"Sarkisyan, Karen S"},{"first_name":"Fyodor","last_name":"Kondrashov","orcid":"0000-0001-8243-4694","full_name":"Kondrashov, Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87"}],"quality_controlled":"1","project":[{"_id":"26580278-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Characterizing the fitness landscape on population and global scales","grant_number":"771209"},{"grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"abstract":[{"lang":"eng","text":"Studies of protein fitness landscapes reveal biophysical constraints guiding protein evolution and empower prediction of functional proteins. However, generalisation of these findings is limited due to scarceness of systematic data on fitness landscapes of proteins with a defined evolutionary relationship. We characterized the fitness peaks of four orthologous fluorescent proteins with a broad range of sequence divergence. While two of the four studied fitness peaks were sharp, the other two were considerably flatter, being almost entirely free of epistatic interactions. Mutationally robust proteins, characterized by a flat fitness peak, were not optimal templates for machine-learning-driven protein design – instead, predictions were more accurate for fragile proteins with epistatic landscapes. Our work paves insights for practical application of fitness landscape heterogeneity in protein engineering."}],"publication_status":"published","title":"Heterogeneity of the GFP fitness landscape and data-driven protein design","publication":"eLife","_id":"11448","oa":1,"ddc":["570"],"file_date_updated":"2022-06-20T07:44:19Z","article_type":"original","publisher":"eLife Sciences Publications","volume":11,"month":"05","date_created":"2022-06-18T09:06:59Z","article_number":"75842","status":"public","intvolume":"        11","isi":1,"oa_version":"Published Version","type":"journal_article","date_updated":"2023-08-03T07:20:15Z","day":"05","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","acknowledgement":"We thank Ondřej Draganov, Rodrigo Redondo, Bor Kavčič, Mia Juračić and Andrea Pauli for discussion and technical advice. We thank Anita Testa Salmazo for advice on resin protein purification, Dmitry Bolotin and the Milaboratory (milaboratory.com) for access to computing and storage infrastructure, and Josef Houser and Eva Fujdiarova for technical assistance and data interpretation. Core facility Biomolecular Interactions and Crystallization of CEITEC Masaryk University is gratefully acknowledged for the obtaining of the scientific data presented in this paper. This research was supported by the Scientific Service Units (SSU) of IST-Austria\r\nthrough resources provided by the Bioimaging Facility (BIF), and the Life Science Facility (LSF). MiSeq and HiSeq NGS sequencing was performed by the Next Generation Sequencing Facility at Vienna BioCenter Core Facilities (VBCF), member of the Vienna BioCenter (VBC), Austria. FACS was performed at the BioOptics Facility of the Institute of Molecular Pathology (IMP), Austria. We also thank the Biomolecular Crystallography Facility in the Vanderbilt University Center for Structural Biology. We are grateful to Joel M Harp for help with X-ray data collection. This work was supported by the ERC Consolidator grant to FAK (771209—CharFL). KSS acknowledges support by President’s Grant МК–5405.2021.1.4, the Imperial College Research Fellowship and the MRC London Institute of Medical Sciences (UKRI MC-A658-5QEA0).\r\nAF is supported by the Marie Skłodowska-Curie Fellowship (H2020-MSCA-IF-2019, Grant Agreement No. 898203, Project acronym \"FLINDIP\"). Experiments were partially carried out using equipment provided by the Institute of Bioorganic Chemistry of the Russian Academy of Sciences Сore Facility (CKP IBCH). This work was supported by a Russian Science Foundation grant 19-74-10102.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665,385.","ec_funded":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"has_accepted_license":"1","department":[{"_id":"GradSch"},{"_id":"FyKo"}],"language":[{"iso":"eng"}],"doi":"10.7554/elife.75842","external_id":{"isi":["000799197200001"]},"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"file":[{"access_level":"open_access","checksum":"7573c28f44028ab0cc81faef30039e44","file_name":"2022_eLife_Somermeyer.pdf","date_updated":"2022-06-20T07:44:19Z","file_id":"11454","success":1,"file_size":5297213,"content_type":"application/pdf","creator":"dernst","date_created":"2022-06-20T07:44:19Z","relation":"main_file"}],"date_published":"2022-05-05T00:00:00Z","scopus_import":"1","publication_identifier":{"issn":["2050-084X"]}},{"volume":25,"issue":"7","publisher":"Elsevier","article_type":"original","file_date_updated":"2022-07-04T08:19:25Z","isi":1,"intvolume":"        25","status":"public","article_number":"104580","month":"07","date_created":"2022-07-03T22:01:33Z","author":[{"first_name":"Katarina","last_name":"Bartalska","full_name":"Bartalska, Katarina","id":"4D883232-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Verena","last_name":"Hübschmann","full_name":"Hübschmann, Verena","id":"32B7C918-F248-11E8-B48F-1D18A9856A87"},{"id":"4B51CE74-F248-11E8-B48F-1D18A9856A87","full_name":"Korkut, Medina","orcid":"0000-0003-4309-2251","last_name":"Korkut","first_name":"Medina"},{"first_name":"Ryan J","last_name":"Cubero","orcid":"0000-0003-0002-1867","full_name":"Cubero, Ryan J","id":"850B2E12-9CD4-11E9-837F-E719E6697425"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro","first_name":"Alessandro","last_name":"Venturino"},{"full_name":"Rössler, Karl","first_name":"Karl","last_name":"Rössler"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","last_name":"Siegert","first_name":"Sandra"}],"quality_controlled":"1","citation":{"apa":"Bartalska, K., Hübschmann, V., Korkut, M., Cubero, R. J., Venturino, A., Rössler, K., … Siegert, S. (2022). A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. <i>IScience</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.isci.2022.104580\">https://doi.org/10.1016/j.isci.2022.104580</a>","mla":"Bartalska, Katarina, et al. “A Systematic Characterization of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” <i>IScience</i>, vol. 25, no. 7, 104580, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.isci.2022.104580\">10.1016/j.isci.2022.104580</a>.","chicago":"Bartalska, Katarina, Verena Hübschmann, Medina Korkut, Ryan J Cubero, Alessandro Venturino, Karl Rössler, Thomas Czech, and Sandra Siegert. “A Systematic Characterization of Microglia-like Cell Occurrence during Retinal Organoid Differentiation.” <i>IScience</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.isci.2022.104580\">https://doi.org/10.1016/j.isci.2022.104580</a>.","short":"K. Bartalska, V. Hübschmann, M. Korkut, R.J. Cubero, A. Venturino, K. Rössler, T. Czech, S. Siegert, IScience 25 (2022).","ista":"Bartalska K, Hübschmann V, Korkut M, Cubero RJ, Venturino A, Rössler K, Czech T, Siegert S. 2022. A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. iScience. 25(7), 104580.","ama":"Bartalska K, Hübschmann V, Korkut M, et al. A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation. <i>iScience</i>. 2022;25(7). doi:<a href=\"https://doi.org/10.1016/j.isci.2022.104580\">10.1016/j.isci.2022.104580</a>","ieee":"K. Bartalska <i>et al.</i>, “A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation,” <i>iScience</i>, vol. 25, no. 7. Elsevier, 2022."},"year":"2022","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"_id":"11478","oa":1,"ddc":["610"],"related_material":{"record":[{"relation":"other","status":"public","id":"12117"}]},"publication":"iScience","title":"A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation","abstract":[{"lang":"eng","text":"Cerebral organoids differentiated from human-induced pluripotent stem cells (hiPSC) provide a unique opportunity to investigate brain development. However, organoids usually lack microglia, brain-resident immune cells, which are present in the early embryonic brain and participate in neuronal circuit development. Here, we find IBA1+ microglia-like cells alongside retinal cups between week 3 and 4 in 2.5D culture with an unguided retinal organoid differentiation protocol. Microglia do not infiltrate the neuroectoderm and instead enrich within non-pigmented, 3D-cystic compartments that develop in parallel to the 3D-retinal organoids. When we guide the retinal organoid differentiation with low-dosed BMP4, we prevent cup development and enhance microglia and 3D-cysts formation. Mass spectrometry identifies these 3D-cysts to express mesenchymal and epithelial markers. We confirmed this microglia-preferred environment also within the unguided protocol, providing insight into microglial behavior and migration and offer a model to study how they enter and distribute within the human brain."}],"publication_status":"published","project":[{"_id":"25D4A630-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Microglia action towards neuronal circuit formation and function in health and disease","grant_number":"715571"},{"name":"IST Austria Open Access Fund","_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854"},{"grant_number":"SC19-017","name":"How human microglia shape developing neurons during health and inflammation","_id":"9B99D380-BA93-11EA-9121-9846C619BF3A"}],"file":[{"relation":"main_file","date_created":"2022-07-04T08:19:25Z","content_type":"application/pdf","creator":"cchlebak","file_size":19400048,"success":1,"file_id":"11480","date_updated":"2022-07-04T08:19:25Z","file_name":"2022_iScience_Bartalska.pdf","checksum":"a470b74e1b3796c710189c81a4cd4329","access_level":"open_access"}],"external_id":{"isi":["000830428500005"]},"date_published":"2022-07-15T00:00:00Z","scopus_import":"1","publication_identifier":{"eissn":["2589-0042"]},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"Yes","day":"15","oa_version":"Published Version","type":"journal_article","date_updated":"2023-11-02T12:21:33Z","has_accepted_license":"1","department":[{"_id":"SaSi"}],"doi":"10.1016/j.isci.2022.104580","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"ec_funded":1,"acknowledgement":"We thank the scientific service units at ISTA, specifically the lab support facility and imaging & optics facility for their support; Nicolas Armel for performing the Mass Spectrometry. We thank Alexandra Lang and Tanja Peilnsteiner for their help in human brain tissue collection, Rouven Schulz for his insights into the functional assays We thank all members of the Siegert group for constant feedback on the project and Margaret Maes, Rouven Schulz, and Marco Benevento for feedback on the manuscript. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung Niederösterreich (grant No. Sc19-017 to V.H.)."},{"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"department":[{"_id":"EvBe"}],"has_accepted_license":"1","doi":"10.1073/pnas.2122460119","language":[{"iso":"eng"}],"acknowledgement":"We acknowledge Hana Semeradova, Juan Carlos Montesinos, Nicola Cavallari, Marc¸al Gallem\u0003ı, Kaori Tabata, Andrej Hurn\u0003y, and Sascha Waidmann for sharing materials; and Marina Borges Osorio for critical reading of the manuscript. Work in the E. Benkova laboratory was supported by the Austrian Science Fund (FWF01_I1774S) to K.O., R.A., and E. Benkova. We acknowledge the Bioimaging Facility and Life Science Facilities of the Institute of Science\r\nand Technology Austria. We give sincere thanks to Hana Martınkova and Petra Amakorova for their help with cytokinin analyses. This work was funded by the Czech Science Foundation (Project No. 19-00973S).","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","oa_version":"Published Version","date_updated":"2023-08-03T12:39:29Z","type":"journal_article","day":"25","scopus_import":"1","publication_identifier":{"eissn":["1091-6490"]},"external_id":{"isi":["000881496900007"],"pmid":["35878040"]},"file":[{"success":1,"date_updated":"2022-08-08T07:09:58Z","file_id":"11744","checksum":"6e97dedc281247fc3fe238a209f14af0","file_name":"2022_PNAS_Abualia.pdf","access_level":"open_access","relation":"main_file","date_created":"2022-08-08T07:09:58Z","file_size":3092330,"creator":"dernst","content_type":"application/pdf"}],"date_published":"2022-07-25T00:00:00Z","pmid":1,"title":"Molecular framework integrating nitrate sensing in root and auxin-guided shoot adaptive responses","publication":"Proceedings of the National Academy of Sciences of the United States of America","_id":"11734","oa":1,"ddc":["570"],"project":[{"_id":"2542D156-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Hormone cross-talk drives nutrient dependent plant development","grant_number":"I 1774-B16"}],"abstract":[{"lang":"eng","text":"Mineral nutrition is one of the key environmental factors determining plant development and growth. Nitrate is the major form of macronutrient nitrogen that plants take up from the soil. Fluctuating availability or deficiency of this element severely limits plant growth and negatively affects crop production in the agricultural system. To cope with the heterogeneity of nitrate distribution in soil, plants evolved a complex regulatory mechanism that allows rapid adjustment of physiological and developmental processes to the status of this nutrient. The root, as a major exploitation organ that controls the uptake of nitrate to the plant body, acts as a regulatory hub that, according to nitrate availability, coordinates the growth and development of other plant organs. Here, we identified a regulatory framework, where cytokinin response factors (CRFs) play a central role as a molecular readout of the nitrate status in roots to guide shoot adaptive developmental response. We show that nitrate-driven activation of NLP7, a master regulator of nitrate response in plants, fine tunes biosynthesis of cytokinin in roots and its translocation to shoots where it enhances expression of CRFs. CRFs, through direct transcriptional regulation of PIN auxin transporters, promote the flow of auxin and thereby stimulate the development of shoot organs."}],"publication_status":"published","citation":{"ama":"Abualia R, Ötvös K, Novák O, et al. Molecular framework integrating nitrate sensing in root and auxin-guided shoot adaptive responses. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2022;119(31). doi:<a href=\"https://doi.org/10.1073/pnas.2122460119\">10.1073/pnas.2122460119</a>","ieee":"R. Abualia <i>et al.</i>, “Molecular framework integrating nitrate sensing in root and auxin-guided shoot adaptive responses,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 119, no. 31. Proceedings of the National Academy of Sciences, 2022.","chicago":"Abualia, Rashed, Krisztina Ötvös, Ondřej Novák, Eleonore Bouguyon, Kevin Domanegg, Anne Krapp, Philip Nacry, Alain Gojon, Benoit Lacombe, and Eva Benková. “Molecular Framework Integrating Nitrate Sensing in Root and Auxin-Guided Shoot Adaptive Responses.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>. Proceedings of the National Academy of Sciences, 2022. <a href=\"https://doi.org/10.1073/pnas.2122460119\">https://doi.org/10.1073/pnas.2122460119</a>.","short":"R. Abualia, K. Ötvös, O. Novák, E. Bouguyon, K. Domanegg, A. Krapp, P. Nacry, A. Gojon, B. Lacombe, E. Benková, Proceedings of the National Academy of Sciences of the United States of America 119 (2022).","ista":"Abualia R, Ötvös K, Novák O, Bouguyon E, Domanegg K, Krapp A, Nacry P, Gojon A, Lacombe B, Benková E. 2022. Molecular framework integrating nitrate sensing in root and auxin-guided shoot adaptive responses. Proceedings of the National Academy of Sciences of the United States of America. 119(31), e2122460119.","apa":"Abualia, R., Ötvös, K., Novák, O., Bouguyon, E., Domanegg, K., Krapp, A., … Benková, E. (2022). Molecular framework integrating nitrate sensing in root and auxin-guided shoot adaptive responses. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. Proceedings of the National Academy of Sciences. <a href=\"https://doi.org/10.1073/pnas.2122460119\">https://doi.org/10.1073/pnas.2122460119</a>","mla":"Abualia, Rashed, et al. “Molecular Framework Integrating Nitrate Sensing in Root and Auxin-Guided Shoot Adaptive Responses.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 119, no. 31, e2122460119, Proceedings of the National Academy of Sciences, 2022, doi:<a href=\"https://doi.org/10.1073/pnas.2122460119\">10.1073/pnas.2122460119</a>."},"quality_controlled":"1","author":[{"orcid":"0000-0002-9357-9415","full_name":"Abualia, Rashed","id":"4827E134-F248-11E8-B48F-1D18A9856A87","last_name":"Abualia","first_name":"Rashed"},{"id":"29B901B0-F248-11E8-B48F-1D18A9856A87","full_name":"Ötvös, Krisztina","orcid":"0000-0002-5503-4983","last_name":"Ötvös","first_name":"Krisztina"},{"full_name":"Novák, Ondřej","first_name":"Ondřej","last_name":"Novák"},{"first_name":"Eleonore","last_name":"Bouguyon","full_name":"Bouguyon, Eleonore"},{"full_name":"Domanegg, Kevin","orcid":"0000-0002-1215-4264","id":"a24c7829-16e8-11ed-8527-c4d36ffb7539","last_name":"Domanegg","first_name":"Kevin"},{"full_name":"Krapp, Anne","last_name":"Krapp","first_name":"Anne"},{"last_name":"Nacry","first_name":"Philip","full_name":"Nacry, Philip"},{"last_name":"Gojon","first_name":"Alain","full_name":"Gojon, Alain"},{"last_name":"Lacombe","first_name":"Benoit","full_name":"Lacombe, Benoit"},{"id":"38F4F166-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8510-9739","full_name":"Benková, Eva","first_name":"Eva","last_name":"Benková"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png"},"year":"2022","intvolume":"       119","isi":1,"month":"07","date_created":"2022-08-07T22:01:57Z","article_number":"e2122460119","status":"public","volume":119,"issue":"31","file_date_updated":"2022-08-08T07:09:58Z","publisher":"Proceedings of the National Academy of Sciences","article_type":"original"},{"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","supervisor":[{"id":"38F4F166-F248-11E8-B48F-1D18A9856A87","full_name":"Benková, Eva","orcid":"0000-0002-8510-9739","last_name":"Benková","first_name":"Eva"}],"day":"17","oa_version":"Published Version","type":"dissertation","date_updated":"2023-09-09T22:30:04Z","department":[{"_id":"GradSch"},{"_id":"EvBe"}],"has_accepted_license":"1","language":[{"iso":"eng"}],"doi":"10.15479/at:ista:11879","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"SSU"}],"acknowledgement":"I would like to acknowledge ISTA and all the people from the Scientific Service Units and at ISTA, in particular Dorota Jaworska for excellent technical and scientific support as well as ÖAW for funding my research for over 3 years (DOC ÖAW Fellowship PR1022OEAW02).","page":"128","file":[{"relation":"main_file","date_created":"2022-08-17T12:08:49Z","file_size":11113608,"content_type":"application/pdf","creator":"cartner","embargo":"2023-09-08","file_id":"11907","date_updated":"2023-09-09T22:30:03Z","file_name":"ChristinaArtner_PhD_Thesis_2022.pdf","checksum":"a2c2fdc28002538840490bfa6a08b2cb","access_level":"open_access"},{"file_size":19097730,"creator":"cartner","content_type":"application/octet-stream","relation":"source_file","embargo_to":"open_access","date_created":"2022-08-17T12:08:59Z","checksum":"66b461c074b815fbe63481b3f46a9f43","file_name":"ChristinaArtner_PhD_Thesis_2022.7z","access_level":"closed","date_updated":"2023-09-09T22:30:03Z","file_id":"11908"}],"keyword":["high ambient temperature","auxin","PINs","Zinc-Finger proteins","thermomorphogenesis","stress"],"date_published":"2022-08-17T00:00:00Z","publication_identifier":{"isbn":["978-3-99078-022-0"],"issn":["2663-337X"]},"alternative_title":["ISTA Thesis"],"author":[{"last_name":"Artner","first_name":"Christina","id":"45DF286A-F248-11E8-B48F-1D18A9856A87","full_name":"Artner, Christina"}],"citation":{"apa":"Artner, C. (2022). <i>Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11879\">https://doi.org/10.15479/at:ista:11879</a>","mla":"Artner, Christina. <i>Modulation of Auxin Transport via ZF Proteins Adjust Plant Response to High Ambient Temperature</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11879\">10.15479/at:ista:11879</a>.","ama":"Artner C. Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11879\">10.15479/at:ista:11879</a>","ieee":"C. Artner, “Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature,” Institute of Science and Technology Austria, 2022.","short":"C. Artner, Modulation of Auxin Transport via ZF Proteins Adjust Plant Response to High Ambient Temperature, Institute of Science and Technology Austria, 2022.","chicago":"Artner, Christina. “Modulation of Auxin Transport via ZF Proteins Adjust Plant Response to High Ambient Temperature.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11879\">https://doi.org/10.15479/at:ista:11879</a>.","ista":"Artner C. 2022. Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature. Institute of Science and Technology Austria."},"year":"2022","_id":"11879","ddc":["580"],"oa":1,"title":"Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature","abstract":[{"text":"As the overall global mean surface temperature is increasing due to climate change, plant\r\nadaptation to those stressful conditions is of utmost importance for their survival. Plants are\r\nsessile organisms, thus to compensate for their lack of mobility, they evolved a variety of\r\nmechanisms enabling them to flexibly adjust their physiological, growth and developmental\r\nprocesses to fluctuating temperatures and to survive in harsh environments. While these unique\r\nadaptation abilities provide an important evolutionary advantage, overall modulation of plant\r\ngrowth and developmental program due to non-optimal temperature negatively affects biomass\r\nproduction, crop productivity or sensitivity to pathogens. Thus, understanding molecular\r\nprocesses underlying plant adaptation to increased temperature can provide important\r\nresources for breeding strategies to ensure sufficient agricultural food production.\r\nAn increase in ambient temperature by a few degrees leads to profound changes in organ growth\r\nincluding enhanced hypocotyl elongation, expansion of petioles, hyponastic growth of leaves and\r\ncotyledons, collectively named thermomorphogenesis (Casal & Balasubramanian, 2019). Auxin,\r\none of the best-studied growth hormones, plays an essential role in this process by direct\r\nactivation of transcriptional and non-transcriptional processes resulting in elongation growth\r\n(Majda & Robert, 2018).To modulate hypocotyl growth in response to high ambient temperature\r\n(hAT), auxin needs to be redistributed accordingly. PINs, auxin efflux transporters, are key\r\ncomponents of the polar auxin transport (PAT) machinery, which controls the amount and\r\ndirection of auxin translocated in the plant tissues and organs(Adamowski & Friml, 2015). Hence,\r\nPIN-mediated transport is tightly linked with thermo-morphogenesis, and interference with PAT\r\nthrough either chemical or genetic means dramatically affecting the adaptive responses to hAT.\r\nIntriguingly, despite the key role of PIN mediated transport in growth response to hAT, whether\r\nand how PINs at the level of expression adapt to fluctuation in temperature is scarcely\r\nunderstood.\r\nWith genetic, molecular and advanced bio-imaging approaches, we demonstrate the role of PIN\r\nauxin transporters in the regulation of hypocotyl growth in response to hAT. We show that via\r\nadjustment of PIN3, PIN4 and PIN7 expression in cotyledons and hypocotyls, auxin distribution is modulated thereby determining elongation pattern of epidermal cells at hAT. Furthermore, we\r\nidentified three Zinc-Finger (ZF) transcription factors as novel molecular components of the\r\nthermo-regulatory network, which through negative regulation of PIN transcription adjust the\r\ntransport of auxin at hAT. Our results suggest that the ZF-PIN module might be a part of the\r\nnegative feedback loop attenuating the activity of the thermo-sensing pathway to restrain\r\nexaggerated growth and developmental responses to hAT.","lang":"eng"}],"publication_status":"published","project":[{"name":"Hormonal regulation of plant adaptive responses to environmental signals","_id":"2685A872-B435-11E9-9278-68D0E5697425"}],"publisher":"Institute of Science and Technology Austria","file_date_updated":"2023-09-09T22:30:03Z","degree_awarded":"PhD","status":"public","month":"08","date_created":"2022-08-17T07:58:53Z"},{"year":"2022","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"author":[{"id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","full_name":"Schulz, Rouven","orcid":"0000-0001-5297-733X","first_name":"Rouven","last_name":"Schulz"}],"citation":{"ista":"Schulz R. 2022. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. Institute of Science and Technology Austria.","short":"R. Schulz, Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function, Institute of Science and Technology Austria, 2022.","chicago":"Schulz, Rouven. “Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11945\">https://doi.org/10.15479/at:ista:11945</a>.","ieee":"R. Schulz, “Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function,” Institute of Science and Technology Austria, 2022.","ama":"Schulz R. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11945\">10.15479/at:ista:11945</a>","mla":"Schulz, Rouven. <i>Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11945\">10.15479/at:ista:11945</a>.","apa":"Schulz, R. (2022). <i>Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11945\">https://doi.org/10.15479/at:ista:11945</a>"},"abstract":[{"text":"G protein-coupled receptors (GPCRs) respond to specific ligands and regulate multiple processes ranging from cell growth and immune responses to neuronal signal transmission. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additional challenges exist to dissect cell-type specific responses when the same GPCR is expressed on several cell types within the body. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that selectively bind their agonist clozapine-N-oxide (CNO) and mimic a GPCR-of-interest in a desired cell type.\r\nWe validated our approach with β2-adrenergic receptor (β2AR/ADRB2) and show that our chimeric DREADD-β2AR triggers comparable responses on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Since β2AR is also enriched in microglia, which can drive inflammation in the central nervous system, we expressed chimeric DREADD-β2AR in primary microglia and successfully recapitulate β2AR-mediated filopodia formation through CNO stimulation. To dissect the role of selected GPCRs during microglial inflammation, we additionally generated DREADD-based chimeras for microglia-enriched GPR65 and GPR109A/HCAR2. In a microglia cell line, DREADD-β2AR and DREADD-GPR65 both modulated the inflammatory response with a similar profile as endogenously expressed β2AR, while DREADD-GPR109A showed no impact.\r\nOur DREADD-based approach provides the means to obtain mechanistic and functional insights into GPCR signaling on a cell-type specific level.","lang":"eng"}],"publication_status":"published","project":[{"_id":"267F75D8-B435-11E9-9278-68D0E5697425","name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling"}],"_id":"11945","related_material":{"record":[{"id":"11995","relation":"dissertation_contains","status":"public"}]},"oa":1,"ddc":["570"],"title":"Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function","publisher":"Institute of Science and Technology Austria","file_date_updated":"2022-08-25T09:33:31Z","status":"public","month":"08","date_created":"2022-08-23T11:33:11Z","degree_awarded":"PhD","supervisor":[{"last_name":"Siegert","first_name":"Sandra","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"}],"day":"23","oa_version":"Published Version","date_updated":"2023-08-03T13:02:26Z","type":"dissertation","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","article_processing_charge":"No","department":[{"_id":"GradSch"},{"_id":"SaSi"}],"has_accepted_license":"1","doi":"10.15479/at:ista:11945","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"}],"page":"133","file":[{"date_updated":"2022-08-25T08:59:57Z","file_id":"11970","success":1,"access_level":"open_access","file_name":"Thesis_Rouven_Schulz_2022_final.pdf","checksum":"61b1b666a210ff7cdd0e95ea75207a13","date_created":"2022-08-25T08:59:57Z","relation":"main_file","content_type":"application/pdf","creator":"rschulz","file_size":28079331},{"file_size":27226963,"creator":"rschulz","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","date_created":"2022-08-25T09:00:11Z","relation":"source_file","access_level":"closed","checksum":"2b8f95ea1c134dbdb927b41b1dbeeeb5","file_name":"Thesis_Rouven_Schulz_2022_final.docx","file_id":"11971","date_updated":"2022-08-25T09:33:31Z"}],"date_published":"2022-08-23T00:00:00Z","publication_identifier":{"issn":["2663-337X"]},"alternative_title":["ISTA Thesis"]},{"volume":13,"publisher":"Springer Nature","article_type":"original","file_date_updated":"2022-08-29T06:44:30Z","isi":1,"intvolume":"        13","article_number":"4728","status":"public","date_created":"2022-08-28T22:01:59Z","month":"08","author":[{"full_name":"Schulz, Rouven","orcid":"0000-0001-5297-733X","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","last_name":"Schulz","first_name":"Rouven"},{"last_name":"Korkut","first_name":"Medina","full_name":"Korkut, Medina","orcid":"0000-0003-4309-2251","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Venturino","first_name":"Alessandro","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gloria","last_name":"Colombo","id":"3483CF6C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9434-8902","full_name":"Colombo, Gloria"},{"last_name":"Siegert","first_name":"Sandra","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"}],"quality_controlled":"1","citation":{"apa":"Schulz, R., Korkut, M., Venturino, A., Colombo, G., &#38; Siegert, S. (2022). Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-32390-1\">https://doi.org/10.1038/s41467-022-32390-1</a>","mla":"Schulz, Rouven, et al. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate Microglia Responses.” <i>Nature Communications</i>, vol. 13, 4728, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-32390-1\">10.1038/s41467-022-32390-1</a>.","ama":"Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-32390-1\">10.1038/s41467-022-32390-1</a>","ieee":"R. Schulz, M. Korkut, A. Venturino, G. Colombo, and S. Siegert, “Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.","ista":"Schulz R, Korkut M, Venturino A, Colombo G, Siegert S. 2022. Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses. Nature Communications. 13, 4728.","short":"R. Schulz, M. Korkut, A. Venturino, G. Colombo, S. Siegert, Nature Communications 13 (2022).","chicago":"Schulz, Rouven, Medina Korkut, Alessandro Venturino, Gloria Colombo, and Sandra Siegert. “Chimeric GPCRs Mimic Distinct Signaling Pathways and Modulate Microglia Responses.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-32390-1\">https://doi.org/10.1038/s41467-022-32390-1</a>."},"year":"2022","tmp":{"image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"ddc":["570"],"oa":1,"related_material":{"link":[{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/dreaddful-mimicry/"}],"record":[{"id":"11945","relation":"part_of_dissertation","status":"public"},{"relation":"research_data","status":"public","id":"11542"}]},"_id":"11995","publication":"Nature Communications","title":"Chimeric GPCRs mimic distinct signaling pathways and modulate microglia responses","pmid":1,"publication_status":"published","abstract":[{"lang":"eng","text":"G protein-coupled receptors (GPCRs) regulate processes ranging from immune responses to neuronal signaling. However, ligands for many GPCRs remain unknown, suffer from off-target effects or have poor bioavailability. Additionally, dissecting cell type-specific responses is challenging when the same GPCR is expressed on different cells within a tissue. Here, we overcome these limitations by engineering DREADD-based GPCR chimeras that bind clozapine-N-oxide and mimic a GPCR-of-interest. We show that chimeric DREADD-β2AR triggers responses comparable to β2AR on second messenger and kinase activity, post-translational modifications, and protein-protein interactions. Moreover, we successfully recapitulate β2AR-mediated filopodia formation in microglia, an immune cell capable of driving central nervous system inflammation. When dissecting microglial inflammation, we included two additional DREADD-based chimeras mimicking microglia-enriched GPR65 and GPR109A. DREADD-β2AR and DREADD-GPR65 modulate the inflammatory response with high similarity to endogenous β2AR, while DREADD-GPR109A shows no impact. Our DREADD-based approach allows investigation of cell type-dependent pathways without known endogenous ligands."}],"project":[{"_id":"267F75D8-B435-11E9-9278-68D0E5697425","name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling"}],"date_published":"2022-08-15T00:00:00Z","external_id":{"pmid":["35970889"],"isi":["000840984400032"]},"file":[{"file_id":"12002","date_updated":"2022-08-29T06:44:30Z","success":1,"access_level":"open_access","file_name":"2022_NatComm_Schulz.pdf","checksum":"191d9db0266e14a28d3a56dc7f65da84","date_created":"2022-08-29T06:44:30Z","relation":"main_file","file_size":7317396,"creator":"cchlebak","content_type":"application/pdf"}],"publication_identifier":{"eissn":["2041-1723"]},"scopus_import":"1","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","day":"15","date_updated":"2024-02-21T12:34:51Z","type":"journal_article","oa_version":"Published Version","doi":"10.1038/s41467-022-32390-1","language":[{"iso":"eng"}],"has_accepted_license":"1","department":[{"_id":"SaSi"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"}],"acknowledgement":"The authors thank the Scientific Service Units at ISTA, in particular the Molecular Biology Service of the Lab Support Facility, Imaging & Optics Facility, and the Preclinical Facility, and the Novarino group, Harald Janoviak, and Marco Benevento for sharing reagents and expertise. This research was supported by a DOC Fellowship (24979) awarded to R.S. by the Austrian Academy of Sciences."},{"publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"scopus_import":"1","date_published":"2022-09-22T00:00:00Z","keyword":["Multidisciplinary"],"external_id":{"isi":["000854788200001"],"pmid":["36104567"]},"file":[{"access_level":"open_access","file_name":"EcCxI_manuscript_rev3_noSI_updated_withFigs_opt.pdf","checksum":"d42a93e24f59e883ef0b5429832391d0","date_updated":"2023-05-30T17:05:31Z","file_id":"13104","success":1,"file_size":1425655,"creator":"lsazanov","content_type":"application/pdf","date_created":"2023-05-30T17:05:31Z","relation":"main_file"},{"file_size":9842513,"creator":"lsazanov","content_type":"application/pdf","date_created":"2023-05-30T17:07:05Z","relation":"main_file","access_level":"open_access","checksum":"5422bc0a73b3daadafa262c7ea6deae3","file_name":"EcCxI_manuscript_rev3_SI_All_opt_upd.pdf","file_id":"13105","date_updated":"2023-05-30T17:07:05Z","success":1}],"page":"808-814","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"},{"_id":"ScienComp"}],"ec_funded":1,"doi":"10.1038/s41586-022-05199-7","language":[{"iso":"eng"}],"department":[{"_id":"LeSa"}],"has_accepted_license":"1","acknowledgement":"This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Electron Microscopy Facility (EMF), the Life Science Facility (LSF) and the IST high-performance computing cluster. We thank V.-V. Hodirnau from IST Austria EMF, M. Babiak from CEITEC for assistance with collecting cryo-EM data and A. Charnagalov for the assistance with protein purification. V.K. was a recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Institute of Science and Technology, Austria. V.K. and O.P. are funded by the ERC Advanced Grant 101020697 RESPICHAIN to L.S. This work was also supported by the Medical Research Council (UK).","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_updated":"2023-08-04T08:54:52Z","type":"journal_article","oa_version":"Submitted Version","day":"22","intvolume":"       609","isi":1,"date_created":"2023-01-12T12:04:33Z","month":"09","status":"public","issue":"7928","volume":609,"file_date_updated":"2023-05-30T17:07:05Z","article_type":"original","publisher":"Springer Nature","publication":"Nature","title":"A universal coupling mechanism of respiratory complex I","pmid":1,"ddc":["572"],"related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1038/s41586-022-05457-8"},{"description":"News on ISTA website","relation":"press_release","url":"https://ista.ac.at/en/news/proton-dominos-kick-off-life/"}],"record":[{"id":"12781","status":"public","relation":"dissertation_contains"}]},"oa":1,"_id":"12138","project":[{"grant_number":"25541","name":"Structural characterization of E. coli complex I: an important mechanistic model","_id":"238A0A5A-32DE-11EA-91FC-C7463DDC885E"},{"grant_number":"101020697","name":"Structure and mechanism of respiratory chain molecular machines","call_identifier":"H2020","_id":"627abdeb-2b32-11ec-9570-ec31a97243d3"}],"publication_status":"published","abstract":[{"lang":"eng","text":"Complex I is the first enzyme in the respiratory chain, which is responsible for energy production in mitochondria and bacteria1. Complex I couples the transfer of two electrons from NADH to quinone and the translocation of four protons across the membrane2, but the coupling mechanism remains contentious. Here we present cryo-electron microscopy structures of Escherichia coli complex I (EcCI) in different redox states, including catalytic turnover. EcCI exists mostly in the open state, in which the quinone cavity is exposed to the cytosol, allowing access for water molecules, which enable quinone movements. Unlike the mammalian paralogues3, EcCI can convert to the closed state only during turnover, showing that closed and open states are genuine turnover intermediates. The open-to-closed transition results in the tightly engulfed quinone cavity being connected to the central axis of the membrane arm, a source of substrate protons. Consistently, the proportion of the closed state increases with increasing pH. We propose a detailed but straightforward and robust mechanism comprising a ‘domino effect’ series of proton transfers and electrostatic interactions: the forward wave (‘dominoes stacking’) primes the pump, and the reverse wave (‘dominoes falling’) results in the ejection of all pumped protons from the distal subunit NuoL. This mechanism explains why protons exit exclusively from the NuoL subunit and is supported by our mutagenesis data. We contend that this is a universal coupling mechanism of complex I and related enzymes."}],"citation":{"mla":"Kravchuk, Vladyslav, et al. “A Universal Coupling Mechanism of Respiratory Complex I.” <i>Nature</i>, vol. 609, no. 7928, Springer Nature, 2022, pp. 808–14, doi:<a href=\"https://doi.org/10.1038/s41586-022-05199-7\">10.1038/s41586-022-05199-7</a>.","apa":"Kravchuk, V., Petrova, O., Kampjut, D., Wojciechowska-Bason, A., Breese, Z., &#38; Sazanov, L. A. (2022). A universal coupling mechanism of respiratory complex I. <i>Nature</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41586-022-05199-7\">https://doi.org/10.1038/s41586-022-05199-7</a>","ista":"Kravchuk V, Petrova O, Kampjut D, Wojciechowska-Bason A, Breese Z, Sazanov LA. 2022. A universal coupling mechanism of respiratory complex I. Nature. 609(7928), 808–814.","chicago":"Kravchuk, Vladyslav, Olga Petrova, Domen Kampjut, Anna Wojciechowska-Bason, Zara Breese, and Leonid A Sazanov. “A Universal Coupling Mechanism of Respiratory Complex I.” <i>Nature</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41586-022-05199-7\">https://doi.org/10.1038/s41586-022-05199-7</a>.","short":"V. Kravchuk, O. Petrova, D. Kampjut, A. Wojciechowska-Bason, Z. Breese, L.A. Sazanov, Nature 609 (2022) 808–814.","ama":"Kravchuk V, Petrova O, Kampjut D, Wojciechowska-Bason A, Breese Z, Sazanov LA. A universal coupling mechanism of respiratory complex I. <i>Nature</i>. 2022;609(7928):808-814. doi:<a href=\"https://doi.org/10.1038/s41586-022-05199-7\">10.1038/s41586-022-05199-7</a>","ieee":"V. Kravchuk, O. Petrova, D. Kampjut, A. Wojciechowska-Bason, Z. Breese, and L. A. Sazanov, “A universal coupling mechanism of respiratory complex I,” <i>Nature</i>, vol. 609, no. 7928. Springer Nature, pp. 808–814, 2022."},"author":[{"full_name":"Kravchuk, Vladyslav","id":"4D62F2A6-F248-11E8-B48F-1D18A9856A87","last_name":"Kravchuk","first_name":"Vladyslav"},{"last_name":"Petrova","first_name":"Olga","full_name":"Petrova, Olga","id":"5D8C9660-5D49-11EA-8188-567B3DDC885E"},{"id":"37233050-F248-11E8-B48F-1D18A9856A87","full_name":"Kampjut, Domen","last_name":"Kampjut","first_name":"Domen"},{"full_name":"Wojciechowska-Bason, Anna","first_name":"Anna","last_name":"Wojciechowska-Bason"},{"full_name":"Breese, Zara","first_name":"Zara","last_name":"Breese"},{"first_name":"Leonid A","last_name":"Sazanov","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989","full_name":"Sazanov, Leonid A"}],"quality_controlled":"1","year":"2022"}]