[{"date_published":"2022-01-10T00:00:00Z","ddc":["570"],"main_file_link":[{"open_access":"1","url":"https://www.sciencedirect.com/science/article/pii/S1534580721009497"}],"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"EM-Fac"}],"publication_status":"published","oa":1,"intvolume":"        57","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12726"},{"relation":"dissertation_contains","id":"14530","status":"public"},{"status":"public","id":"12401","relation":"dissertation_contains"}]},"citation":{"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>","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.","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>.","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>","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.","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."},"status":"public","external_id":{"pmid":["34919802"],"isi":["000768933800005"]},"volume":57,"date_created":"2022-01-30T23:01:33Z","page":"47-62.e9","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"}],"date_updated":"2024-03-25T23:30:12Z","oa_version":"Published Version","type":"journal_article","month":"01","_id":"10703","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.","year":"2022","doi":"10.1016/j.devcel.2021.11.024","quality_controlled":"1","publication_identifier":{"eissn":["1878-1551"],"issn":["1534-5807"]},"isi":1,"language":[{"iso":"eng"}],"issue":"1","project":[{"_id":"260AA4E2-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","grant_number":"747687"},{"name":"Cellular navigation along spatial gradients","call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373"}],"title":"WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues","author":[{"first_name":"Florian","last_name":"Gaertner","full_name":"Gaertner, Florian"},{"first_name":"Patricia","last_name":"Reis-Rodrigues","full_name":"Reis-Rodrigues, Patricia"},{"last_name":"De Vries","first_name":"Ingrid","full_name":"De Vries, Ingrid","id":"4C7D837E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hons","first_name":"Miroslav","id":"4167FE56-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6625-3348","full_name":"Hons, Miroslav"},{"full_name":"Aguilera, Juan","last_name":"Aguilera","first_name":"Juan"},{"last_name":"Riedl","first_name":"Michael","id":"3BE60946-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4844-6311","full_name":"Riedl, Michael"},{"last_name":"Leithner","first_name":"Alexander F","orcid":"0000-0002-1073-744X","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87","full_name":"Leithner, Alexander F"},{"first_name":"Saren","last_name":"Tasciyan","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1671-393X","full_name":"Tasciyan, Saren"},{"last_name":"Kopf","first_name":"Aglaja","full_name":"Kopf, Aglaja","orcid":"0000-0002-2187-6656","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87"},{"id":"4515C308-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5145-4609","full_name":"Merrin, Jack","last_name":"Merrin","first_name":"Jack"},{"first_name":"Vanessa","last_name":"Zheden","full_name":"Zheden, Vanessa","id":"39C5A68A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9438-4783"},{"last_name":"Kaufmann","first_name":"Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","full_name":"Kaufmann, Walter"},{"first_name":"Robert","last_name":"Hauschild","id":"4E01D6B4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9843-3522","full_name":"Hauschild, Robert"},{"id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","full_name":"Sixt, Michael K","last_name":"Sixt","first_name":"Michael K"}],"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","day":"10","publication":"Developmental Cell","article_processing_charge":"No","ec_funded":1,"scopus_import":"1","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"article_type":"original","publisher":"Cell Press ; Elsevier","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","pmid":1,"department":[{"_id":"MiSi"},{"_id":"EM-Fac"},{"_id":"NanoFab"},{"_id":"BjHo"}]},{"quality_controlled":"1","doi":"10.3389/fonc.2022.777634","publication_identifier":{"issn":["2234-943X"]},"language":[{"iso":"eng"}],"isi":1,"project":[{"name":"Investigating the role of the novel major superfamily facilitator transporter family member MFSD1 in metastasis","_id":"2637E9C0-B435-11E9-9278-68D0E5697425","grant_number":"LSC16-021 "}],"title":"The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis","article_number":"777634","license":"https://creativecommons.org/licenses/by/4.0/","day":"08","file":[{"file_name":"2022_FrontiersOncol_Roblek.pdf","success":1,"file_size":6303227,"content_type":"application/pdf","relation":"main_file","creator":"cchlebak","file_id":"10751","date_updated":"2022-02-08T13:26:40Z","checksum":"63dfecf30c5bbf9408b3512bd603f78c","date_created":"2022-02-08T13:26:40Z","access_level":"open_access"}],"author":[{"last_name":"Roblek","first_name":"Marko","id":"3047D808-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9588-1389","full_name":"Roblek, Marko"},{"first_name":"Julia","last_name":"Bicher","full_name":"Bicher, Julia","id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"van Gogh, Merel","last_name":"van Gogh","first_name":"Merel"},{"last_name":"György","first_name":"Attila","full_name":"György, Attila","orcid":"0000-0002-1819-198X","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Seeböck","first_name":"Rita","full_name":"Seeböck, Rita"},{"first_name":"Bozena","last_name":"Szulc","full_name":"Szulc, Bozena"},{"full_name":"Damme, Markus","last_name":"Damme","first_name":"Markus"},{"first_name":"Mariusz","last_name":"Olczak","full_name":"Olczak, Mariusz"},{"full_name":"Borsig, Lubor","first_name":"Lubor","last_name":"Borsig"},{"last_name":"Siekhaus","first_name":"Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","full_name":"Siekhaus, Daria E"}],"article_processing_charge":"Yes (via OA deal)","scopus_import":"1","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication":"Frontiers in Oncology","department":[{"_id":"DaSi"}],"publisher":"Frontiers","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","acknowledged_ssus":[{"_id":"Bio"}],"date_published":"2022-02-08T00:00:00Z","ddc":["570"],"has_accepted_license":"1","publication_status":"published","oa":1,"citation":{"ama":"Roblek M, Bicher J, van Gogh M, et al. The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. <i>Frontiers in Oncology</i>. 2022;12. doi:<a href=\"https://doi.org/10.3389/fonc.2022.777634\">10.3389/fonc.2022.777634</a>","apa":"Roblek, M., Bicher, J., van Gogh, M., György, A., Seeböck, R., Szulc, B., … Siekhaus, D. E. (2022). The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. <i>Frontiers in Oncology</i>. Frontiers. <a href=\"https://doi.org/10.3389/fonc.2022.777634\">https://doi.org/10.3389/fonc.2022.777634</a>","ista":"Roblek M, Bicher J, van Gogh M, György A, Seeböck R, Szulc B, Damme M, Olczak M, Borsig L, Siekhaus DE. 2022. The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. Frontiers in Oncology. 12, 777634.","mla":"Roblek, Marko, et al. “The Solute Carrier MFSD1 Decreases Β1 Integrin’s Activation Status and Thus Tumor Metastasis.” <i>Frontiers in Oncology</i>, vol. 12, 777634, Frontiers, 2022, doi:<a href=\"https://doi.org/10.3389/fonc.2022.777634\">10.3389/fonc.2022.777634</a>.","chicago":"Roblek, Marko, Julia Bicher, Merel van Gogh, Attila György, Rita Seeböck, Bozena Szulc, Markus Damme, Mariusz Olczak, Lubor Borsig, and Daria E Siekhaus. “The Solute Carrier MFSD1 Decreases Β1 Integrin’s Activation Status and Thus Tumor Metastasis.” <i>Frontiers in Oncology</i>. Frontiers, 2022. <a href=\"https://doi.org/10.3389/fonc.2022.777634\">https://doi.org/10.3389/fonc.2022.777634</a>.","ieee":"M. Roblek <i>et al.</i>, “The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis,” <i>Frontiers in Oncology</i>, vol. 12. Frontiers, 2022.","short":"M. Roblek, J. Bicher, M. van Gogh, A. György, R. Seeböck, B. Szulc, M. Damme, M. Olczak, L. Borsig, D.E. Siekhaus, Frontiers in Oncology 12 (2022)."},"intvolume":"        12","related_material":{"link":[{"description":"News on IST Homepage","url":"https://ist.ac.at/en/news/suppressing-the-spread-of-tumors/","relation":"confirmation"}]},"status":"public","external_id":{"isi":["000760618800001"]},"file_date_updated":"2022-02-08T13:26:40Z","date_created":"2022-02-01T10:33:50Z","volume":12,"date_updated":"2023-08-02T14:05:44Z","abstract":[{"text":"Solute carriers are increasingly recognized as participating in a plethora of pathologies, including cancer. We describe here the involvement of the orphan solute carrier MFSD1 in the regulation of tumor cell migration. Loss of MFSD1 enabled higher levels of metastasis in a mouse model. We identified an increased migratory potential in MFSD1-/- tumor cells which was mediated by increased focal adhesion turn-over, reduced stability of mature inactive β1 integrin, and the resulting increased integrin activation index. We show that MFSD1 promoted recycling to the cell surface of endocytosed inactive β1 integrin and thereby protected β1 integrin from proteolytic degradation; this led to dampening of the integrin activation index. Furthermore, down-regulation of MFSD1 expression was observed during early steps of tumorigenesis and higher MFSD1 expression levels correlate with a better cancer patient prognosis. In sum, we describe a requirement for endolysosomal MFSD1 in efficient β1 integrin recycling to suppress tumor spread.","lang":"eng"}],"month":"02","type":"journal_article","oa_version":"Published Version","_id":"10712","year":"2022","acknowledgement":"We thank M. Sixt, A. Leithner, and J. Alanko for helpful advice and the BioImaging Facility at IST Austria for technical support and assistance. We thank the Siekhaus Lab for the careful review of the manuscript and their input. MR and DS were funded by the NO Forschungs- und Bildungsges.m.b.H. (LS16-021) and IST core funding. MD was funded by Deutsche Forschungsgemeinschaft (DA 1785-1)."},{"publication":"Science","article_processing_charge":"No","article_type":"original","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"American Association for the Advancement of Science","pmid":1,"department":[{"_id":"DaSi"}],"title":"Cell division in tissues enables macrophage infiltration","author":[{"id":"3425EC26-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1522-3162","full_name":"Akhmanova, Maria","first_name":"Maria","last_name":"Akhmanova"},{"orcid":"0000-0001-6981-6938","id":"49D32318-F248-11E8-B48F-1D18A9856A87","full_name":"Emtenani, Shamsi","first_name":"Shamsi","last_name":"Emtenani"},{"full_name":"Krueger, Daniel","last_name":"Krueger","first_name":"Daniel"},{"last_name":"György","first_name":"Attila","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1819-198X","full_name":"György, Attila"},{"last_name":"Pereira Guarda","first_name":"Mariana","full_name":"Pereira Guarda, Mariana","id":"6de81d9d-e2f2-11eb-945a-af8bc2a60b26"},{"first_name":"Mikhail","last_name":"Vlasov","full_name":"Vlasov, Mikhail"},{"last_name":"Vlasov","first_name":"Fedor","full_name":"Vlasov, Fedor"},{"first_name":"Andrei","last_name":"Akopian","full_name":"Akopian, Andrei"},{"last_name":"Ratheesh","first_name":"Aparna","id":"2F064CFE-F248-11E8-B48F-1D18A9856A87","full_name":"Ratheesh, Aparna"},{"full_name":"De Renzis, Stefano","last_name":"De Renzis","first_name":"Stefano"},{"full_name":"Siekhaus, Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","first_name":"Daria E","last_name":"Siekhaus"}],"day":"22","isi":1,"language":[{"iso":"eng"}],"issue":"6591","project":[{"grant_number":"M02379","name":"Modeling epithelial tissue mechanics during cell invasion","_id":"264CBBAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"doi":"10.1126/science.abj0425","quality_controlled":"1","publication_identifier":{"issn":["0036-8075"]},"_id":"10713","acknowledgement":"We thank J. Friml, C. Guet, T. Hurd, M. Fendrych and members of the laboratory for comments on the manuscript; the Bioimaging Facility of IST Austria for excellent support and T. Lecuit, E. Hafen, R. Levayer and A. Martin for fly strains. This work was supported by a grant from the Austrian Science Fund FWF: Lise Meitner Fellowship M2379-B28 to M.A and D.S., and internal funding from IST Austria to D.S. and EMBL to S.D.R.","year":"2022","volume":376,"date_created":"2022-02-01T11:23:18Z","page":"394-396","date_updated":"2023-08-02T14:06:15Z","abstract":[{"text":"Cells migrate through crowded microenvironments within tissues during normal development, immune response, and cancer metastasis. Although migration through pores and tracks in the extracellular matrix (ECM) has been well studied, little is known about cellular traversal into confining cell-dense tissues. We find that embryonic tissue invasion by Drosophila macrophages requires division of an epithelial ectodermal cell at the site of entry. Dividing ectodermal cells disassemble ECM attachment formed by integrin-mediated focal adhesions next to mesodermal cells, allowing macrophages to move their nuclei ahead and invade between two immediately adjacent tissues. Invasion efficiency depends on division frequency, but reduction of adhesion strength allows macrophage entry independently of division. This work demonstrates that tissue dynamics can regulate cellular infiltration.","lang":"eng"}],"month":"04","oa_version":"Preprint","type":"journal_article","intvolume":"       376","citation":{"ieee":"M. Akhmanova <i>et al.</i>, “Cell division in tissues enables macrophage infiltration,” <i>Science</i>, vol. 376, no. 6591. American Association for the Advancement of Science, pp. 394–396, 2022.","chicago":"Akhmanova, Maria, Shamsi Emtenani, Daniel Krueger, Attila György, Mariana Pereira Guarda, Mikhail Vlasov, Fedor Vlasov, et al. “Cell Division in Tissues Enables Macrophage Infiltration.” <i>Science</i>. American Association for the Advancement of Science, 2022. <a href=\"https://doi.org/10.1126/science.abj0425\">https://doi.org/10.1126/science.abj0425</a>.","short":"M. Akhmanova, S. Emtenani, D. Krueger, A. György, M. Pereira Guarda, M. Vlasov, F. Vlasov, A. Akopian, A. Ratheesh, S. De Renzis, D.E. Siekhaus, Science 376 (2022) 394–396.","ama":"Akhmanova M, Emtenani S, Krueger D, et al. Cell division in tissues enables macrophage infiltration. <i>Science</i>. 2022;376(6591):394-396. doi:<a href=\"https://doi.org/10.1126/science.abj0425\">10.1126/science.abj0425</a>","mla":"Akhmanova, Maria, et al. “Cell Division in Tissues Enables Macrophage Infiltration.” <i>Science</i>, vol. 376, no. 6591, American Association for the Advancement of Science, 2022, pp. 394–96, doi:<a href=\"https://doi.org/10.1126/science.abj0425\">10.1126/science.abj0425</a>.","ista":"Akhmanova M, Emtenani S, Krueger D, György A, Pereira Guarda M, Vlasov M, Vlasov F, Akopian A, Ratheesh A, De Renzis S, Siekhaus DE. 2022. Cell division in tissues enables macrophage infiltration. Science. 376(6591), 394–396.","apa":"Akhmanova, M., Emtenani, S., Krueger, D., György, A., Pereira Guarda, M., Vlasov, M., … Siekhaus, D. E. (2022). Cell division in tissues enables macrophage infiltration. <i>Science</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/science.abj0425\">https://doi.org/10.1126/science.abj0425</a>"},"external_id":{"isi":["000788553700039"],"pmid":["35446632"]},"status":"public","date_published":"2022-04-22T00:00:00Z","main_file_link":[{"url":"https://doi.org/10.1101/2021.04.19.438995","open_access":"1"}],"acknowledged_ssus":[{"_id":"Bio"}],"publication_status":"published","oa":1},{"volume":119,"file_date_updated":"2022-02-21T08:45:11Z","date_created":"2022-02-20T23:01:31Z","type":"journal_article","oa_version":"Published Version","month":"02","date_updated":"2023-08-02T14:26:51Z","abstract":[{"lang":"eng","text":"Tension of the actomyosin cell cortex plays a key role in determining cell–cell contact growth and size. The level of cortical tension outside of the cell–cell contact, when pulling at the contact edge, scales with the total size to which a cell–cell contact can grow [J.-L. Maître et al., Science 338, 253–256 (2012)]. Here, we show in zebrafish primary germ-layer progenitor cells that this monotonic relationship only applies to a narrow range of cortical tension increase and that above a critical threshold, contact size inversely scales with cortical tension. This switch from cortical tension increasing to decreasing progenitor cell–cell contact size is caused by cortical tension promoting E-cadherin anchoring to the actomyosin cytoskeleton, thereby increasing clustering and stability of E-cadherin at the contact. After tension-mediated E-cadherin stabilization at the contact exceeds a critical threshold level, the rate by which the contact expands in response to pulling forces from the cortex sharply drops, leading to smaller contacts at physiologically relevant timescales of contact formation. Thus, the activity of cortical tension in expanding cell–cell contact size is limited by tension-stabilizing E-cadherin–actin complexes at the contact."}],"_id":"10766","acknowledgement":"We thank Guillaume Salbreaux, Silvia Grigolon, Edouard Hannezo, and Vanessa Barone for discussions and comments on the manuscript and Shayan Shamipour and Daniel Capek for help with data analysis. We also thank the Imaging & Optics, Electron Microscopy, and Zebrafish Facility Scientific Service Units at the Institute of Science and Technology Austria (ISTA)Nasser Darwish-Miranda  for continuous support. We acknowledge Hitoshi Morita for the gift of VinculinB-GFP plasmid. This research was supported by an ISTA Fellow Marie-Curie Co-funding of regional, national, and international programmes Grant P_IST_EU01 (to J.S.), European Molecular Biology Organization Long-Term Fellowship Grant, ALTF reference number: 187-2013 (to M.S.), Schroedinger Fellowship J4332-B28 (to M.S.), and European Research Council Advanced Grant (MECSPEC; to C.-P.H.).","year":"2022","date_published":"2022-02-14T00:00:00Z","ddc":["570"],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"EM-Fac"},{"_id":"PreCl"}],"publication_status":"published","oa":1,"has_accepted_license":"1","intvolume":"       119","related_material":{"record":[{"relation":"earlier_version","status":"public","id":"9750"}]},"citation":{"ieee":"J. Slovakova <i>et al.</i>, “Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells,” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 119, no. 8. Proceedings of the National Academy of Sciences, 2022.","chicago":"Slovakova, Jana, Mateusz K Sikora, Feyza N Arslan, Silvia Caballero Mancebo, Gabriel Krens, Walter Kaufmann, Jack Merrin, and Carl-Philipp J Heisenberg. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion in Zebrafish Germ-Layer Progenitor Cells.” <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.2122030119\">https://doi.org/10.1073/pnas.2122030119</a>.","short":"J. Slovakova, M.K. Sikora, F.N. Arslan, S. Caballero Mancebo, G. Krens, W. Kaufmann, J. Merrin, C.-P.J. Heisenberg, Proceedings of the National Academy of Sciences of the United States of America 119 (2022).","ama":"Slovakova J, Sikora MK, Arslan FN, et al. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. <i>Proceedings of the National Academy of Sciences of the United States of America</i>. 2022;119(8). doi:<a href=\"https://doi.org/10.1073/pnas.2122030119\">10.1073/pnas.2122030119</a>","mla":"Slovakova, Jana, et al. “Tension-Dependent Stabilization of E-Cadherin Limits Cell-Cell Contact Expansion in Zebrafish Germ-Layer Progenitor Cells.” <i>Proceedings of the National Academy of Sciences of the United States of America</i>, vol. 119, no. 8, e2122030119, Proceedings of the National Academy of Sciences, 2022, doi:<a href=\"https://doi.org/10.1073/pnas.2122030119\">10.1073/pnas.2122030119</a>.","ista":"Slovakova J, Sikora MK, Arslan FN, Caballero Mancebo S, Krens G, Kaufmann W, Merrin J, Heisenberg C-PJ. 2022. Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. Proceedings of the National Academy of Sciences of the United States of America. 119(8), e2122030119.","apa":"Slovakova, J., Sikora, M. K., Arslan, F. N., Caballero Mancebo, S., Krens, G., Kaufmann, W., … Heisenberg, C.-P. J. (2022). Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells. <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.2122030119\">https://doi.org/10.1073/pnas.2122030119</a>"},"status":"public","external_id":{"isi":["000766926900009"]},"article_number":"e2122030119","title":"Tension-dependent stabilization of E-cadherin limits cell-cell contact expansion in zebrafish germ-layer progenitor cells","author":[{"full_name":"Slovakova, Jana","id":"30F3F2F0-F248-11E8-B48F-1D18A9856A87","last_name":"Slovakova","first_name":"Jana"},{"full_name":"Sikora, Mateusz K","id":"2F74BCDE-F248-11E8-B48F-1D18A9856A87","last_name":"Sikora","first_name":"Mateusz K"},{"orcid":"0000-0001-5809-9566","id":"49DA7910-F248-11E8-B48F-1D18A9856A87","full_name":"Arslan, Feyza N","first_name":"Feyza N","last_name":"Arslan"},{"id":"2F1E1758-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5223-3346","full_name":"Caballero Mancebo, Silvia","last_name":"Caballero Mancebo","first_name":"Silvia"},{"first_name":"Gabriel","last_name":"Krens","full_name":"Krens, Gabriel","orcid":"0000-0003-4761-5996","id":"2B819732-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kaufmann, Walter","orcid":"0000-0001-9735-5315","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","last_name":"Kaufmann","first_name":"Walter"},{"full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87","first_name":"Jack","last_name":"Merrin"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","id":"39427864-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0912-4566","full_name":"Heisenberg, Carl-Philipp J"}],"file":[{"success":1,"file_name":"2022_PNAS_Slovakova.pdf","content_type":"application/pdf","relation":"main_file","file_size":1609678,"creator":"dernst","date_updated":"2022-02-21T08:45:11Z","file_id":"10780","checksum":"d49f83c3580613966f71768ddb9a55a5","date_created":"2022-02-21T08:45:11Z","access_level":"open_access"}],"day":"14","publication":"Proceedings of the National Academy of Sciences of the United States of America","article_type":"original","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"scopus_import":"1","ec_funded":1,"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Proceedings of the National Academy of Sciences","department":[{"_id":"CaHe"},{"_id":"EM-Fac"},{"_id":"Bio"}],"doi":"10.1073/pnas.2122030119","quality_controlled":"1","publication_identifier":{"eissn":["10916490"]},"isi":1,"issue":"8","language":[{"iso":"eng"}],"project":[{"grant_number":"291734","call_identifier":"FP7","_id":"25681D80-B435-11E9-9278-68D0E5697425","name":"International IST Postdoc Fellowship Programme"},{"call_identifier":"H2020","_id":"260F1432-B435-11E9-9278-68D0E5697425","name":"Interaction and feedback between cell mechanics and fate specification in vertebrate gastrulation","grant_number":"742573"},{"grant_number":"187-2013","_id":"2521E28E-B435-11E9-9278-68D0E5697425","name":"Modulation of adhesion function in cell-cell contact formation by cortical tension"}]},{"quality_controlled":"1","doi":"10.1093/oons/kvac009","publication_identifier":{"eissn":["2753-149X"]},"issue":"1","language":[{"iso":"eng"}],"project":[{"name":"Molecular Mechanisms of Cerebral Cortex Development","_id":"25D61E48-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","grant_number":"618444"},{"grant_number":"24812","name":"Molecular Mechanisms of Radial Neuronal Migration","_id":"2625A13E-B435-11E9-9278-68D0E5697425"}],"article_number":"kvac009","title":"Tissue-wide effects override cell-intrinsic gene function in radial neuron migration","file":[{"date_created":"2023-08-16T08:00:30Z","access_level":"open_access","file_id":"14061","date_updated":"2023-08-16T08:00:30Z","checksum":"822e76e056c07099d1fb27d1ece5941b","file_size":4846551,"content_type":"application/pdf","relation":"main_file","creator":"dernst","file_name":"2023_OxfordOpenNeuroscience_Hansen.pdf","success":1}],"day":"07","author":[{"full_name":"Hansen, Andi H","id":"38853E16-F248-11E8-B48F-1D18A9856A87","first_name":"Andi H","last_name":"Hansen"},{"first_name":"Florian","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian"},{"full_name":"Riedl, Michael","orcid":"0000-0003-4844-6311","id":"3BE60946-F248-11E8-B48F-1D18A9856A87","first_name":"Michael","last_name":"Riedl"},{"id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen","first_name":"Carmen","last_name":"Streicher"},{"full_name":"Heger, Anna-Magdalena","id":"4B76FFD2-F248-11E8-B48F-1D18A9856A87","last_name":"Heger","first_name":"Anna-Magdalena"},{"last_name":"Laukoter","first_name":"Susanne","id":"2D6B7A9A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7903-3010","full_name":"Laukoter, Susanne"},{"first_name":"Christoph M","last_name":"Sommer","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105"},{"last_name":"Nicolas","first_name":"Armel","full_name":"Nicolas, Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Hof","first_name":"Björn","id":"3A374330-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2057-2754","full_name":"Hof, Björn"},{"first_name":"Li Huei","last_name":"Tsai","full_name":"Tsai, Li Huei"},{"last_name":"Rülicke","first_name":"Thomas","full_name":"Rülicke, Thomas"},{"id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon"}],"article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ec_funded":1,"article_processing_charge":"No","publication":"Oxford Open Neuroscience","department":[{"_id":"SiHi"},{"_id":"BjHo"},{"_id":"LifeSc"},{"_id":"EM-Fac"}],"publisher":"Oxford Academic","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"Bio"}],"ddc":["570"],"date_published":"2022-07-07T00:00:00Z","has_accepted_license":"1","publication_status":"published","oa":1,"citation":{"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>.","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.","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).","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>","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>","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.","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>."},"related_material":{"record":[{"id":"12726","status":"public","relation":"dissertation_contains"},{"status":"public","id":"14530","relation":"dissertation_contains"}]},"intvolume":"         1","status":"public","file_date_updated":"2023-08-16T08:00:30Z","date_created":"2022-02-25T07:52:11Z","volume":1,"oa_version":"Published Version","type":"journal_article","month":"07","date_updated":"2023-11-30T10:55:12Z","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."}],"_id":"10791","year":"2022","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."},{"_id":"10826","year":"2022","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).","date_created":"2022-03-06T23:01:52Z","file_date_updated":"2022-03-07T07:39:25Z","volume":11,"oa_version":"Published Version","type":"journal_article","month":"02","date_updated":"2023-08-02T14:42:55Z","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"}],"citation":{"ista":"Valperga G, de Bono M. 2022. Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in Caenorhabditis elegans. eLife. 11, e68040.","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>.","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>","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>","short":"G. Valperga, M. de Bono, ELife 11 (2022).","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.","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>."},"intvolume":"        11","external_id":{"pmid":["35201977"],"isi":["000763432300001"]},"status":"public","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"ScienComp"}],"ddc":["570"],"date_published":"2022-02-24T00:00:00Z","has_accepted_license":"1","publication_status":"published","oa":1,"article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_processing_charge":"No","scopus_import":"1","publication":"eLife","department":[{"_id":"MaDe"}],"pmid":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"eLife Sciences Publications","article_number":"e68040","title":"Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in Caenorhabditis elegans","day":"24","file":[{"checksum":"cc1b9bf866d0f61f965556e0dd03d3ac","date_updated":"2022-03-07T07:39:25Z","file_id":"10830","access_level":"open_access","date_created":"2022-03-07T07:39:25Z","success":1,"file_name":"2022_eLife_Valperga.pdf","creator":"dernst","relation":"main_file","content_type":"application/pdf","file_size":4095591}],"author":[{"last_name":"Valperga","first_name":"Giulio","id":"67F289DE-0D8F-11EA-9BDD-54AE3DDC885E","full_name":"Valperga, Giulio"},{"first_name":"Mario","last_name":"De Bono","full_name":"De Bono, Mario","orcid":"0000-0001-8347-0443","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87"}],"language":[{"iso":"eng"}],"isi":1,"project":[{"grant_number":"209504/A/17/Z","_id":"23870BE8-32DE-11EA-91FC-C7463DDC885E","name":"Molecular mechanisms of neural circuit function"}],"quality_controlled":"1","doi":"10.7554/eLife.68040","publication_identifier":{"eissn":["2050084X"]}},{"department":[{"_id":"DaSi"},{"_id":"LoSw"}],"publisher":"Embo Press","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_processing_charge":"Yes (via OA deal)","scopus_import":"1","ec_funded":1,"publication":"The Embo Journal","file":[{"file_name":"Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosopila.pdf","file_size":4344585,"content_type":"application/pdf","relation":"main_file","creator":"siekhaus","file_id":"10919","date_updated":"2022-03-24T13:22:41Z","checksum":"dba48580fe0fefaa4c63078d1d2a35df","date_created":"2022-03-24T13:22:41Z","access_level":"open_access"}],"day":"23","author":[{"full_name":"Emtenani, Shamsi","id":"49D32318-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6981-6938","last_name":"Emtenani","first_name":"Shamsi"},{"last_name":"Martin","first_name":"Elliot T","full_name":"Martin, Elliot T"},{"full_name":"György, Attila","orcid":"0000-0002-1819-198X","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","last_name":"György","first_name":"Attila"},{"first_name":"Julia","last_name":"Bicher","id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","full_name":"Bicher, Julia"},{"first_name":"Jakob-Wendelin","last_name":"Genger","full_name":"Genger, Jakob-Wendelin"},{"full_name":"Köcher, Thomas","last_name":"Köcher","first_name":"Thomas"},{"last_name":"Akhmanova","first_name":"Maria","full_name":"Akhmanova, Maria","id":"3425EC26-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1522-3162"},{"last_name":"Pereira Guarda","first_name":"Mariana","id":"6de81d9d-e2f2-11eb-945a-af8bc2a60b26","full_name":"Pereira Guarda, Mariana"},{"id":"3047D808-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9588-1389","full_name":"Roblek, Marko","last_name":"Roblek","first_name":"Marko"},{"last_name":"Bergthaler","first_name":"Andreas","full_name":"Bergthaler, Andreas"},{"first_name":"Thomas R","last_name":"Hurd","full_name":"Hurd, Thomas R"},{"full_name":"Rangan, Prashanth","first_name":"Prashanth","last_name":"Rangan"},{"orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","full_name":"Siekhaus, Daria E","first_name":"Daria E","last_name":"Siekhaus"}],"article_number":"e109049","title":"Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila","project":[{"grant_number":"334077","call_identifier":"FP7","_id":"2536F660-B435-11E9-9278-68D0E5697425","name":"Investigating the role of transporters in invasive migration through junctions"},{"grant_number":"M02379","_id":"264CBBAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Modeling epithelial tissue mechanics during cell invasion"},{"grant_number":"P29638","name":"Drosophila TNFa´s Funktion in Immunzellen","_id":"253B6E48-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"language":[{"iso":"eng"}],"isi":1,"publication_identifier":{"eissn":["1460-2075"]},"quality_controlled":"1","doi":"10.15252/embj.2021109049","year":"2022","acknowledgement":"We thank the DGRC (NIH grant 2P40OD010949-10A1) for plasmids, the BDSC (NIH grant P40OD018537) and the VDRC for fly stocks, FlyBase for essential genomic information, the BDGP in situ database for data (Tomancak et al, 2007), the IST Austria Bioimaging facility for support, the VBC Core Facilities for RNA sequencing and analysis, and C. Guet, C. Navarro, C. Desplan, T. Lecuit, I. Miguel-Aliaga, and Siekhaus group members for comments on the manuscript. The VBCF Metabolomics Facility is funded by the City of Vienna through the Vienna Business Agency. This work was supported by the Marie Curie CIG 334077/IRTIM (DES), Austrian Science Fund (FWF) Lise Meitner Fellowship M2379-B28 (MA and DES), Austrian Science Fund (FWF) grant ASI_FWF01_P29638S (DES), NIH/NIGMS (R01GM111779-06 (PR), RO1GM135628-01 (PR), European Research Council (ERC) grant no. 677006 “CMIL” (AB), and Natural Sciences and Engineering Research Council of Canada\r\n(RGPIN-2019-06766) (TRH). ","_id":"10918","oa_version":"Published Version","type":"journal_article","month":"03","abstract":[{"lang":"eng","text":"Cellular metabolism must adapt to changing demands to enable homeostasis. During immune responses or cancer metastasis, cells leading migration into challenging environments require an energy boost, but what controls this capacity is unclear. Here, we study a previously uncharacterized nuclear protein, Atossa (encoded by CG9005), which supports macrophage invasion into the germband of Drosophila by controlling cellular metabolism. First, nuclear Atossa increases mRNA levels of Porthos, a DEAD-box protein, and of two metabolic enzymes, lysine-α-ketoglutarate reductase (LKR/SDH) and NADPH glyoxylate reductase (GR/HPR), thus enhancing mitochondrial bioenergetics. Then Porthos supports ribosome assembly and thereby raises the translational efficiency of a subset of mRNAs, including those affecting mitochondrial functions, the electron transport chain, and metabolism. Mitochondrial respiration measurements, metabolomics, and live imaging indicate that Atossa and Porthos power up OxPhos and energy production to promote the forging of a path into tissues by leading macrophages. Since many crucial physiological responses require increases in mitochondrial energy output, this previously undescribed genetic program may modulate a wide range of cellular behaviors."}],"date_updated":"2023-08-03T06:13:14Z","date_created":"2022-03-24T13:23:09Z","file_date_updated":"2022-03-24T13:22:41Z","volume":41,"external_id":{"isi":["000771957000001"]},"status":"public","citation":{"ieee":"S. Emtenani <i>et al.</i>, “Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila,” <i>The Embo Journal</i>, vol. 41. Embo Press, 2022.","chicago":"Emtenani, Shamsi, Elliot T Martin, Attila György, Julia Bicher, Jakob-Wendelin Genger, Thomas Köcher, Maria Akhmanova, et al. “Macrophage Mitochondrial Bioenergetics and Tissue Invasion Are Boosted by an Atossa-Porthos Axis in Drosophila.” <i>The Embo Journal</i>. Embo Press, 2022. <a href=\"https://doi.org/10.15252/embj.2021109049\">https://doi.org/10.15252/embj.2021109049</a>.","short":"S. Emtenani, E.T. Martin, A. György, J. Bicher, J.-W. Genger, T. Köcher, M. Akhmanova, M. Pereira Guarda, M. Roblek, A. Bergthaler, T.R. Hurd, P. Rangan, D.E. Siekhaus, The Embo Journal 41 (2022).","ama":"Emtenani S, Martin ET, György A, et al. Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila. <i>The Embo Journal</i>. 2022;41. doi:<a href=\"https://doi.org/10.15252/embj.2021109049\">10.15252/embj.2021109049</a>","mla":"Emtenani, Shamsi, et al. “Macrophage Mitochondrial Bioenergetics and Tissue Invasion Are Boosted by an Atossa-Porthos Axis in Drosophila.” <i>The Embo Journal</i>, vol. 41, e109049, Embo Press, 2022, doi:<a href=\"https://doi.org/10.15252/embj.2021109049\">10.15252/embj.2021109049</a>.","ista":"Emtenani S, Martin ET, György A, Bicher J, Genger J-W, Köcher T, Akhmanova M, Pereira Guarda M, Roblek M, Bergthaler A, Hurd TR, Rangan P, Siekhaus DE. 2022. Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila. The Embo Journal. 41, e109049.","apa":"Emtenani, S., Martin, E. T., György, A., Bicher, J., Genger, J.-W., Köcher, T., … Siekhaus, D. E. (2022). Macrophage mitochondrial bioenergetics and tissue invasion are boosted by an Atossa-Porthos axis in Drosophila. <i>The Embo Journal</i>. Embo Press. <a href=\"https://doi.org/10.15252/embj.2021109049\">https://doi.org/10.15252/embj.2021109049</a>"},"intvolume":"        41","has_accepted_license":"1","publication_status":"published","oa":1,"acknowledged_ssus":[{"_id":"Bio"}],"date_published":"2022-03-23T00:00:00Z","ddc":["570"]},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_processing_charge":"No","ec_funded":1,"department":[{"_id":"GradSch"},{"_id":"MaLo"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Institute of Science and Technology Austria","title":"In vitro reconstitution of Escherichia coli divisome activation","file":[{"success":1,"file_name":"Inventory for Data 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","id":"40136C2A-F248-11E8-B48F-1D18A9856A87","full_name":"Radler, Philipp"}],"keyword":["Bacterial cell division","in vitro reconstitution","FtsZ","FtsN","FtsA"],"project":[{"name":"Self-Organization of the Bacterial Cell","_id":"2595697A-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"679239"},{"grant_number":"P34607","_id":"fc38323b-9c52-11eb-aca3-ff8afb4a011d","name":"Understanding bacterial cell division by in vitro\r\nreconstitution"}],"contributor":[{"last_name":"Loose","first_name":"Martin","contributor_type":"supervisor","id":"462D4284-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7309-9724"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","contributor_type":"researcher","first_name":"Christoph M"},{"last_name":"Caldas","first_name":"Paulo","contributor_type":"researcher"},{"first_name":"David","contributor_type":"researcher","last_name":"Michalik","id":"B9577E20-AA38-11E9-AC9A-0930E6697425"},{"last_name":"Baranova","contributor_type":"researcher","first_name":"Natalia"}],"doi":"10.15479/AT:ISTA:10934","_id":"10934","year":"2022","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. 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.","date_created":"2022-03-31T11:32:32Z","file_date_updated":"2022-04-22T10:15:19Z","type":"research_data","month":"04","oa_version":"Submitted Version","abstract":[{"lang":"eng","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. "}],"date_updated":"2024-02-21T12:35:18Z","citation":{"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>","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>.","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>","short":"P. Radler, (2022).","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>.","ieee":"P. Radler, “In vitro reconstitution of Escherichia coli divisome activation.” Institute of Science and Technology Austria, 2022."},"related_material":{"link":[{"relation":"software","description":"A custom written code (FRAPdiff) to quantify the Off binding rate and Diffusion coefficient of membrane bound proteins. Written by Christoph Sommer.","url":"https://doi.org/10.5281/zenodo.6400639"}],"record":[{"status":"public","id":"11373","relation":"used_in_publication"},{"relation":"used_in_publication","id":"14280","status":"public"}]},"status":"public","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"ddc":["572"],"date_published":"2022-04-05T00:00:00Z","has_accepted_license":"1","oa":1},{"publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-016-9"]},"doi":"10.15479/at:ista:11128","language":[{"iso":"eng"}],"author":[{"last_name":"Matejovicova","first_name":"Lenka","id":"2DFDEC72-F248-11E8-B48F-1D18A9856A87","full_name":"Matejovicova, Lenka"}],"day":"06","file":[{"access_level":"open_access","date_created":"2022-04-07T08:11:34Z","checksum":"e9609bc4e8f8e20146fc1125fd4f1bf7","file_id":"11129","date_updated":"2022-04-07T08:11:34Z","creator":"cchlebak","file_size":11906472,"content_type":"application/pdf","relation":"main_file","file_name":"LenkaPhD_Official_PDFA.pdf"},{"date_created":"2022-04-07T08:11:51Z","access_level":"closed","file_id":"11130","date_updated":"2022-04-07T08:11:51Z","checksum":"99d67040432fd07a225643a212ee8588","file_size":23036766,"content_type":"application/x-zip-compressed","relation":"source_file","creator":"cchlebak","file_name":"LenkaPhD Official_source.zip"}],"title":"Genetic basis of flower colour as a model for adaptive evolution","degree_awarded":"PhD","publisher":"Institute of Science and Technology Austria","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","department":[{"_id":"GradSch"},{"_id":"NiBa"}],"article_processing_charge":"No","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"oa":1,"publication_status":"published","has_accepted_license":"1","supervisor":[{"last_name":"Barton","first_name":"Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240","full_name":"Barton, Nicholas H"}],"date_published":"2022-04-06T00:00:00Z","ddc":["576","582"],"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"}],"alternative_title":["ISTA Thesis"],"status":"public","citation":{"apa":"Matejovicova, L. (2022). <i>Genetic basis of flower colour as a model for adaptive evolution</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:11128\">https://doi.org/10.15479/at:ista:11128</a>","mla":"Matejovicova, Lenka. <i>Genetic Basis of Flower Colour as a Model for Adaptive Evolution</i>. Institute of Science and Technology Austria, 2022, doi:<a href=\"https://doi.org/10.15479/at:ista:11128\">10.15479/at:ista:11128</a>.","ista":"Matejovicova L. 2022. Genetic basis of flower colour as a model for adaptive evolution. Institute of Science and Technology Austria.","ama":"Matejovicova L. Genetic basis of flower colour as a model for adaptive evolution. 2022. doi:<a href=\"https://doi.org/10.15479/at:ista:11128\">10.15479/at:ista:11128</a>","short":"L. Matejovicova, Genetic Basis of Flower Colour as a Model for Adaptive Evolution, Institute of Science and Technology Austria, 2022.","chicago":"Matejovicova, Lenka. “Genetic Basis of Flower Colour as a Model for Adaptive Evolution.” Institute of Science and Technology Austria, 2022. <a href=\"https://doi.org/10.15479/at:ista:11128\">https://doi.org/10.15479/at:ista:11128</a>.","ieee":"L. Matejovicova, “Genetic basis of flower colour as a model for adaptive evolution,” Institute of Science and Technology Austria, 2022."},"page":"112","abstract":[{"text":"Although we often see studies focusing on simple or even discrete traits in studies of colouration,\r\nthe variation of “appearance” phenotypes found in nature is often more complex, continuous\r\nand high-dimensional. Therefore, we developed automated methods suitable for large datasets\r\nof genomes and images, striving to account for their complex nature, while minimising human\r\nbias. We used these methods on a dataset of more than 20, 000 plant SNP genomes and\r\ncorresponding fower images from a hybrid zone of two subspecies of Antirrhinum majus with\r\ndistinctly coloured fowers to improve our understanding of the genetic nature of the fower\r\ncolour in our study system.\r\nFirstly, we use the advantage of large numbers of genotyped plants to estimate the haplotypes in\r\nthe main fower colour regulating region. We study colour- and geography-related characteristics\r\nof the estimated haplotypes and how they connect to their relatedness. We show discrepancies\r\nfrom the expected fower colour distributions given the genotype and identify particular\r\nhaplotypes leading to unexpected phenotypes. We also confrm a signifcant defcit of the\r\ndouble recessive recombinant and quite surprisingly, we show that haplotypes of the most\r\nfrequent parental type are much less variable than others.\r\nSecondly, we introduce our pipeline capable of processing tens of thousands of full fower\r\nimages without human interaction and summarising each image into a set of informative scores.\r\nWe show the compatibility of these machine-measured fower colour scores with the previously\r\nused manual scores and study impact of external efect on the resulting scores. Finally, we use\r\nthe machine-measured fower colour scores to ft and examine a phenotype cline across the\r\nhybrid zone in Planoles using full fower images as opposed to discrete, manual scores and\r\ncompare it with the genotypic cline.","lang":"eng"}],"date_updated":"2023-06-23T06:26:41Z","type":"dissertation","oa_version":"Published Version","month":"04","file_date_updated":"2022-04-07T08:11:51Z","date_created":"2022-04-07T08:19:54Z","year":"2022","_id":"11128"},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","article_processing_charge":"Yes","ec_funded":1,"publication":"Cell Reports","department":[{"_id":"JoDa"},{"_id":"GaNo"}],"pmid":1,"publisher":"Elsevier","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","article_number":"110615","title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","file":[{"access_level":"open_access","date_created":"2022-04-15T09:06:25Z","checksum":"b4e8d68f0268dec499af333e6fd5d8e1","date_updated":"2022-04-15T09:06:25Z","file_id":"11164","creator":"dernst","content_type":"application/pdf","relation":"main_file","file_size":"7808644","success":1,"file_name":"2022_CellReports_Villa.pdf"}],"day":"05","author":[{"full_name":"Villa, Carlo Emanuele","last_name":"Villa","first_name":"Carlo Emanuele"},{"last_name":"Cheroni","first_name":"Cristina","full_name":"Cheroni, Cristina"},{"first_name":"Christoph","last_name":"Dotter","full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096"},{"last_name":"López-Tóbon","first_name":"Alejandro","full_name":"López-Tóbon, Alejandro"},{"first_name":"Bárbara","last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara"},{"id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","full_name":"Sacco, Roberto","first_name":"Roberto","last_name":"Sacco"},{"first_name":"Aysan Çerağ","last_name":"Yahya","full_name":"Yahya, Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87"},{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin","first_name":"Jasmin","last_name":"Morandell"},{"last_name":"Gabriele","first_name":"Michele","full_name":"Gabriele, Michele"},{"full_name":"Tavakoli, Mojtaba","orcid":"0000-0002-7667-6854","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","last_name":"Tavakoli","first_name":"Mojtaba"},{"first_name":"Julia","last_name":"Lyudchik","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer"},{"first_name":"Mariano","last_name":"Gabitto","full_name":"Gabitto, Mariano"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G"},{"full_name":"Testa, Giuseppe","last_name":"Testa","first_name":"Giuseppe"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino"}],"issue":"1","language":[{"iso":"eng"}],"keyword":["General Biochemistry","Genetics and Molecular Biology"],"isi":1,"project":[{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","call_identifier":"FWF","_id":"2690FEAC-B435-11E9-9278-68D0E5697425","grant_number":"I04205"}],"quality_controlled":"1","doi":"10.1016/j.celrep.2022.110615","publication_identifier":{"issn":["2211-1247"]},"_id":"11160","year":"2022","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.","date_created":"2022-04-15T09:03:10Z","file_date_updated":"2022-04-15T09:06:25Z","volume":39,"month":"04","oa_version":"Published Version","type":"journal_article","date_updated":"2024-03-25T23:30:25Z","abstract":[{"lang":"eng","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."}],"citation":{"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>","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).","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.","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>."},"related_material":{"record":[{"status":"public","id":"12364","relation":"dissertation_contains"}]},"intvolume":"        39","external_id":{"pmid":["35385734"],"isi":["000785983900003"]},"status":"public","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"date_published":"2022-04-05T00:00:00Z","ddc":["570"],"has_accepted_license":"1","oa":1,"publication_status":"published"},{"quality_controlled":"1","doi":"10.1126/sciadv.abq1263","publication_identifier":{"issn":["2375-2548"]},"language":[{"iso":"eng"}],"issue":"44","project":[{"grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"},{"grant_number":"T0101031","name":"Role of Eed in neural stem cell lineage progression","call_identifier":"FWF","_id":"268F8446-B435-11E9-9278-68D0E5697425"}],"title":"Tissue-wide genetic and cellular landscape shapes the execution of sequential PRC2 functions in neural stem cell lineage progression","article_number":"abq1263","file":[{"checksum":"0117023e188542082ca6693cf39e7f03","file_id":"12742","date_updated":"2023-03-21T14:18:10Z","access_level":"open_access","date_created":"2023-03-21T14:18:10Z","file_name":"sciadv.abq1263.pdf","success":1,"creator":"patrickd","file_size":2973998,"content_type":"application/pdf","relation":"main_file"}],"day":"01","author":[{"first_name":"Nicole","last_name":"Amberg","orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole"},{"full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","last_name":"Pauler"},{"last_name":"Streicher","first_name":"Carmen","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen"},{"last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon"}],"ec_funded":1,"article_processing_charge":"No","scopus_import":"1","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"publication":"Science Advances","department":[{"_id":"SiHi"}],"publisher":"American Association for the Advancement of Science","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"LifeSc"}],"ddc":["570"],"date_published":"2022-11-01T00:00:00Z","has_accepted_license":"1","publication_status":"published","oa":1,"citation":{"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>","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>","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>.","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.","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>.","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.","short":"N. Amberg, F. Pauler, C. Streicher, S. Hippenmeyer, Science Advances 8 (2022)."},"related_material":{"link":[{"description":"News on ISTA website","url":"https://ista.ac.at/en/news/whole-tissue-shapes-brain-development/","relation":"press_release"}]},"intvolume":"         8","status":"public","date_created":"2022-04-26T15:04:50Z","file_date_updated":"2023-03-21T14:18:10Z","volume":8,"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."}],"date_updated":"2023-05-31T12:24:10Z","month":"11","oa_version":"Published Version","type":"journal_article","_id":"11336","year":"2022","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."},{"month":"05","oa_version":"Published Version","type":"journal_article","date_updated":"2023-08-03T06:44:50Z","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"}],"page":"113-118","date_created":"2022-05-01T22:01:42Z","file_date_updated":"2022-08-05T06:08:24Z","volume":605,"year":"2022","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.","_id":"11341","has_accepted_license":"1","oa":1,"publication_status":"published","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"Bio"}],"date_published":"2022-05-05T00:00:00Z","ddc":["570"],"external_id":{"pmid":["35444278"],"isi":["000784934100003"]},"status":"public","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>","ista":"Lukacisin M, Espinosa-Cantú A, Bollenbach MT. 2022. Intron-mediated induction of phenotypic heterogeneity. Nature. 605, 113–118.","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>.","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>","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.","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>.","short":"M. Lukacisin, A. Espinosa-Cantú, M.T. Bollenbach, Nature 605 (2022) 113–118."},"intvolume":"       605","file":[{"success":1,"file_name":"2022_Nature_Lukacisin.pdf","content_type":"application/pdf","relation":"main_file","file_size":25360311,"creator":"dernst","date_updated":"2022-08-05T06:08:24Z","file_id":"11727","checksum":"d68cd1596bb9fd819b750fe47c8a138a","date_created":"2022-08-05T06:08:24Z","access_level":"open_access"}],"day":"05","author":[{"id":"298FFE8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6549-4177","full_name":"Lukacisin, Martin","last_name":"Lukacisin","first_name":"Martin"},{"first_name":"Adriana","last_name":"Espinosa-Cantú","full_name":"Espinosa-Cantú, Adriana"},{"last_name":"Bollenbach","first_name":"Mark Tobias","full_name":"Bollenbach, Mark Tobias","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X"}],"title":"Intron-mediated induction of phenotypic heterogeneity","pmid":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Springer Nature","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","scopus_import":"1","article_processing_charge":"No","ec_funded":1,"publication":"Nature","publication_identifier":{"issn":["0028-0836"],"eissn":["1476-4687"]},"quality_controlled":"1","doi":"10.1038/s41586-022-04633-0","project":[{"_id":"25E83C2C-B435-11E9-9278-68D0E5697425","call_identifier":"FP7","name":"Optimality principles in responses to antibiotics","grant_number":"303507"},{"_id":"25E9AF9E-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Revealing the mechanisms underlying drug interactions","grant_number":"P27201-B22"}],"language":[{"iso":"eng"}],"isi":1},{"project":[{"grant_number":"679239","_id":"2595697A-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Self-Organization of the Bacterial Cell"},{"name":"Understanding bacterial cell division by in vitro\r\nreconstitution","_id":"fc38323b-9c52-11eb-aca3-ff8afb4a011d","grant_number":"P34607"}],"keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry"],"isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2041-1723"]},"doi":"10.1038/s41467-022-30301-y","quality_controlled":"1","publisher":"Springer Nature","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"MaLo"}],"publication":"Nature Communications","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_processing_charge":"No","ec_funded":1,"scopus_import":"1","author":[{"last_name":"Radler","first_name":"Philipp","full_name":"Radler, Philipp","orcid":"0000-0001-9198-2182 ","id":"40136C2A-F248-11E8-B48F-1D18A9856A87"},{"id":"38661662-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3086-9124","full_name":"Baranova, Natalia S.","first_name":"Natalia S.","last_name":"Baranova"},{"full_name":"Dos Santos Caldas, Paulo R","orcid":"0000-0001-6730-4461","id":"38FCDB4C-F248-11E8-B48F-1D18A9856A87","last_name":"Dos Santos Caldas","first_name":"Paulo R"},{"last_name":"Sommer","first_name":"Christoph M","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105"},{"id":"319AA9CE-F248-11E8-B48F-1D18A9856A87","full_name":"Lopez Pelegrin, Maria D","first_name":"Maria D","last_name":"Lopez Pelegrin"},{"full_name":"Michalik, David","id":"B9577E20-AA38-11E9-AC9A-0930E6697425","first_name":"David","last_name":"Michalik"},{"first_name":"Martin","last_name":"Loose","id":"462D4284-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7309-9724","full_name":"Loose, Martin"}],"day":"12","file":[{"creator":"dernst","content_type":"application/pdf","relation":"main_file","file_size":6945191,"success":1,"file_name":"2022_NatureCommunications_Radler.pdf","access_level":"open_access","date_created":"2022-05-13T09:10:51Z","checksum":"5af863ee1b95a0710f6ee864d68dc7a6","date_updated":"2022-05-13T09:10:51Z","file_id":"11374"}],"article_number":"2635","title":"In vitro reconstitution of Escherichia coli divisome activation","status":"public","external_id":{"isi":["000795171100037"]},"intvolume":"        13","related_material":{"record":[{"status":"public","id":"14280","relation":"dissertation_contains"},{"relation":"research_data","id":"10934","status":"public"}],"link":[{"url":"https://doi.org/10.1038/s41467-022-34485-1","relation":"erratum"}]},"citation":{"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.","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.","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>.","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)."},"oa":1,"publication_status":"published","has_accepted_license":"1","ddc":["570"],"date_published":"2022-05-12T00:00:00Z","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) 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.","year":"2022","_id":"11373","oa_version":"Published Version","month":"05","type":"journal_article","date_updated":"2024-02-21T12:35:18Z","abstract":[{"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.","lang":"eng"}],"volume":13,"date_created":"2022-05-13T09:06:28Z","file_date_updated":"2022-05-13T09:10:51Z"},{"doi":"10.7554/elife.75842","quality_controlled":"1","publication_identifier":{"issn":["2050-084X"]},"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"isi":1,"language":[{"iso":"eng"}],"project":[{"name":"Characterizing the fitness landscape on population and global scales","_id":"26580278-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"771209"},{"grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"}],"article_number":"75842","title":"Heterogeneity of the GFP fitness landscape and data-driven protein design","author":[{"full_name":"Gonzalez Somermeyer, Louisa","id":"4720D23C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9139-5383","last_name":"Gonzalez Somermeyer","first_name":"Louisa"},{"first_name":"Aubin","last_name":"Fleiss","full_name":"Fleiss, Aubin"},{"last_name":"Mishin","first_name":"Alexander S","full_name":"Mishin, Alexander S"},{"full_name":"Bozhanova, Nina G","first_name":"Nina G","last_name":"Bozhanova"},{"last_name":"Igolkina","first_name":"Anna A","full_name":"Igolkina, Anna A"},{"first_name":"Jens","last_name":"Meiler","full_name":"Meiler, Jens"},{"full_name":"Alaball Pujol, Maria-Elisenda","first_name":"Maria-Elisenda","last_name":"Alaball Pujol"},{"full_name":"Putintseva, Ekaterina V","last_name":"Putintseva","first_name":"Ekaterina V"},{"first_name":"Karen S","last_name":"Sarkisyan","full_name":"Sarkisyan, Karen S"},{"last_name":"Kondrashov","first_name":"Fyodor","full_name":"Kondrashov, Fyodor","orcid":"0000-0001-8243-4694","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87"}],"day":"05","file":[{"file_size":5297213,"content_type":"application/pdf","relation":"main_file","creator":"dernst","file_name":"2022_eLife_Somermeyer.pdf","success":1,"date_created":"2022-06-20T07:44:19Z","access_level":"open_access","file_id":"11454","date_updated":"2022-06-20T07:44:19Z","checksum":"7573c28f44028ab0cc81faef30039e44"}],"publication":"eLife","article_type":"original","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_processing_charge":"No","ec_funded":1,"scopus_import":"1","publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"GradSch"},{"_id":"FyKo"}],"ddc":["570"],"date_published":"2022-05-05T00:00:00Z","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"oa":1,"publication_status":"published","has_accepted_license":"1","intvolume":"        11","citation":{"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>","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.","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>.","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>.","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."},"status":"public","external_id":{"isi":["000799197200001"]},"volume":11,"file_date_updated":"2022-06-20T07:44:19Z","date_created":"2022-06-18T09:06:59Z","oa_version":"Published Version","month":"05","type":"journal_article","date_updated":"2023-08-03T07:20:15Z","abstract":[{"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.","lang":"eng"}],"_id":"11448","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.","year":"2022"},{"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.).","year":"2022","_id":"11478","type":"journal_article","month":"07","oa_version":"Published Version","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."}],"date_updated":"2023-11-02T12:21:33Z","volume":25,"date_created":"2022-07-03T22:01:33Z","file_date_updated":"2022-07-04T08:19:25Z","status":"public","external_id":{"isi":["000830428500005"]},"intvolume":"        25","related_material":{"record":[{"relation":"other","id":"12117","status":"public"}]},"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>.","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>","short":"K. Bartalska, V. Hübschmann, M. Korkut, R.J. Cubero, A. Venturino, K. Rössler, T. Czech, S. Siegert, IScience 25 (2022).","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>.","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."},"publication_status":"published","oa":1,"has_accepted_license":"1","ddc":["610"],"date_published":"2022-07-15T00:00:00Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"publisher":"Elsevier","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"SaSi"}],"publication":"iScience","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","ec_funded":1,"scopus_import":"1","article_processing_charge":"Yes","author":[{"last_name":"Bartalska","first_name":"Katarina","id":"4D883232-F248-11E8-B48F-1D18A9856A87","full_name":"Bartalska, Katarina"},{"full_name":"Hübschmann, Verena","id":"32B7C918-F248-11E8-B48F-1D18A9856A87","last_name":"Hübschmann","first_name":"Verena"},{"id":"4B51CE74-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4309-2251","full_name":"Korkut, Medina","first_name":"Medina","last_name":"Korkut"},{"full_name":"Cubero, Ryan J","orcid":"0000-0003-0002-1867","id":"850B2E12-9CD4-11E9-837F-E719E6697425","first_name":"Ryan J","last_name":"Cubero"},{"full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","first_name":"Alessandro"},{"full_name":"Rössler, Karl","first_name":"Karl","last_name":"Rössler"},{"full_name":"Czech, Thomas","last_name":"Czech","first_name":"Thomas"},{"last_name":"Siegert","first_name":"Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra"}],"day":"15","file":[{"relation":"main_file","content_type":"application/pdf","file_size":19400048,"creator":"cchlebak","success":1,"file_name":"2022_iScience_Bartalska.pdf","date_created":"2022-07-04T08:19:25Z","access_level":"open_access","date_updated":"2022-07-04T08:19:25Z","file_id":"11480","checksum":"a470b74e1b3796c710189c81a4cd4329"}],"article_number":"104580","title":"A systematic characterization of microglia-like cell occurrence during retinal organoid differentiation","project":[{"grant_number":"715571","_id":"25D4A630-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Microglia action towards neuronal circuit formation and function in health and disease"},{"_id":"B67AFEDC-15C9-11EA-A837-991A96BB2854","name":"IST Austria Open Access Fund"},{"grant_number":"SC19-017","_id":"9B99D380-BA93-11EA-9121-9846C619BF3A","name":"How human microglia shape developing neurons during health and inflammation"}],"isi":1,"issue":"7","language":[{"iso":"eng"}],"publication_identifier":{"eissn":["2589-0042"]},"doi":"10.1016/j.isci.2022.104580","quality_controlled":"1"},{"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"date_published":"2022-07-25T00:00:00Z","ddc":["570"],"has_accepted_license":"1","publication_status":"published","oa":1,"citation":{"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).","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>.","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>.","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>","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>"},"intvolume":"       119","status":"public","external_id":{"isi":["000881496900007"],"pmid":["35878040"]},"file_date_updated":"2022-08-08T07:09:58Z","date_created":"2022-08-07T22:01:57Z","volume":119,"oa_version":"Published Version","type":"journal_article","month":"07","date_updated":"2023-08-03T12:39:29Z","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."}],"_id":"11734","year":"2022","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).","quality_controlled":"1","doi":"10.1073/pnas.2122460119","publication_identifier":{"eissn":["1091-6490"]},"issue":"31","language":[{"iso":"eng"}],"isi":1,"project":[{"grant_number":"I 1774-B16","call_identifier":"FWF","_id":"2542D156-B435-11E9-9278-68D0E5697425","name":"Hormone cross-talk drives nutrient dependent plant development"}],"article_number":"e2122460119","title":"Molecular framework integrating nitrate sensing in root and auxin-guided shoot adaptive responses","day":"25","file":[{"date_created":"2022-08-08T07:09:58Z","access_level":"open_access","file_id":"11744","date_updated":"2022-08-08T07:09:58Z","checksum":"6e97dedc281247fc3fe238a209f14af0","file_size":3092330,"content_type":"application/pdf","relation":"main_file","creator":"dernst","file_name":"2022_PNAS_Abualia.pdf","success":1}],"author":[{"first_name":"Rashed","last_name":"Abualia","orcid":"0000-0002-9357-9415","id":"4827E134-F248-11E8-B48F-1D18A9856A87","full_name":"Abualia, Rashed"},{"first_name":"Krisztina","last_name":"Ötvös","id":"29B901B0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-5503-4983","full_name":"Ötvös, Krisztina"},{"last_name":"Novák","first_name":"Ondřej","full_name":"Novák, Ondřej"},{"full_name":"Bouguyon, Eleonore","first_name":"Eleonore","last_name":"Bouguyon"},{"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"},{"first_name":"Philip","last_name":"Nacry","full_name":"Nacry, Philip"},{"last_name":"Gojon","first_name":"Alain","full_name":"Gojon, Alain"},{"full_name":"Lacombe, Benoit","first_name":"Benoit","last_name":"Lacombe"},{"id":"38F4F166-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8510-9739","full_name":"Benková, Eva","last_name":"Benková","first_name":"Eva"}],"article_type":"original","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"scopus_import":"1","article_processing_charge":"No","publication":"Proceedings of the National Academy of Sciences of the United States of America","department":[{"_id":"EvBe"}],"pmid":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Proceedings of the National Academy of Sciences"},{"oa":1,"publication_status":"published","has_accepted_license":"1","ddc":["570"],"date_published":"2022-07-26T00:00:00Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"EM-Fac"}],"status":"public","external_id":{"isi":["000838410200001"]},"intvolume":"        11","related_material":{"record":[{"id":"10316","status":"public","relation":"earlier_version"}]},"citation":{"ama":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>","mla":"Tomasek, Kathrin, et al. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>, vol. 11, e78995, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.78995\">10.7554/eLife.78995</a>.","ista":"Tomasek K, Leithner AF, Glatzová I, Lukesch MS, Guet CC, Sixt MK. 2022. Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. eLife. 11, e78995.","apa":"Tomasek, K., Leithner, A. F., Glatzová, I., Lukesch, M. S., Guet, C. C., &#38; Sixt, M. K. (2022). Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>","ieee":"K. Tomasek, A. F. Leithner, I. Glatzová, M. S. Lukesch, C. C. Guet, and M. K. Sixt, “Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","chicago":"Tomasek, Kathrin, Alexander F Leithner, Ivana Glatzová, Michael S. Lukesch, Calin C Guet, and Michael K Sixt. “Type 1 Piliated Uropathogenic Escherichia Coli Hijack the Host Immune Response by Binding to CD14.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.78995\">https://doi.org/10.7554/eLife.78995</a>.","short":"K. Tomasek, A.F. Leithner, I. Glatzová, M.S. Lukesch, C.C. Guet, M.K. Sixt, ELife 11 (2022)."},"date_updated":"2023-08-03T12:54:21Z","abstract":[{"lang":"eng","text":"A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on mouse dendritic cells (DCs) as a binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of the pathogenic strain CFT073 to CD14 reduced DC migration by overactivation of integrins and blunted expression of co-stimulatory molecules by overactivating the NFAT (nuclear factor of activated T-cells) pathway, both rate-limiting factors of T cell activation. This response was binary at the single-cell level, but averaged in larger populations exposed to both piliated and non-piliated pathogens, presumably via the exchange of immunomodulatory cytokines. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease."}],"month":"07","oa_version":"Published Version","type":"journal_article","volume":11,"file_date_updated":"2022-08-16T08:57:37Z","date_created":"2022-08-14T22:01:46Z","acknowledgement":"We thank Ulrich Dobrindt for providing UPEC strains CFT073, UTI89, and 536, Frank Assen, Vlad Gavra, Maximilian Götz, Bor Kavčič, Jonna Alanko, and Eva Kiermaier for help with experiments and Robert Hauschild, Julian Stopp, and Saren Tasciyan for help with data analysis. We thank the IST Austria Scientific Service Units, especially the Bioimaging facility, the Preclinical facility and the Electron microscopy facility for technical support, Jakob Wallner and all members of the Guet and Sixt lab for fruitful discussions and Daria Siekhaus for critically reading the manuscript. This work was supported by grants from the Austrian Research Promotion Agency (FEMtech 868984) to IG, the European Research Council (CoG 724373), and the Austrian Science Fund (FWF P29911) to MS.","year":"2022","_id":"11843","publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/eLife.78995","quality_controlled":"1","project":[{"_id":"25FE9508-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Cellular navigation along spatial gradients","grant_number":"724373"},{"name":"Mechanical adaptation of lamellipodial actin","_id":"26018E70-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"P29911"}],"isi":1,"language":[{"iso":"eng"}],"author":[{"full_name":"Tomasek, Kathrin","id":"3AEC8556-F248-11E8-B48F-1D18A9856A87","first_name":"Kathrin","last_name":"Tomasek"},{"first_name":"Alexander F","last_name":"Leithner","full_name":"Leithner, Alexander F","id":"3B1B77E4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Ivana","last_name":"Glatzová","full_name":"Glatzová, Ivana","id":"727b3c7d-4939-11ec-89b3-b9b0750ab74d"},{"full_name":"Lukesch, Michael S.","first_name":"Michael S.","last_name":"Lukesch"},{"last_name":"Guet","first_name":"Calin C","orcid":"0000-0001-6220-2052","id":"47F8433E-F248-11E8-B48F-1D18A9856A87","full_name":"Guet, Calin C"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","first_name":"Michael K"}],"day":"26","file":[{"file_name":"2022_eLife_Tomasek.pdf","success":1,"creator":"cchlebak","file_size":2057577,"content_type":"application/pdf","relation":"main_file","checksum":"002a3c7c7ea5caa9af9cfbea308f6ea4","file_id":"11861","date_updated":"2022-08-16T08:57:37Z","access_level":"open_access","date_created":"2022-08-16T08:57:37Z"}],"title":"Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14","article_number":"e78995","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"eLife Sciences Publications","department":[{"_id":"MiSi"},{"_id":"CaGu"}],"publication":"eLife","scopus_import":"1","ec_funded":1,"article_processing_charge":"Yes","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original"},{"year":"2022","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).","_id":"11879","oa_version":"Published Version","type":"dissertation","month":"08","abstract":[{"lang":"eng","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."}],"date_updated":"2023-09-09T22:30:04Z","page":"128","file_date_updated":"2023-09-09T22:30:03Z","date_created":"2022-08-17T07:58:53Z","status":"public","alternative_title":["ISTA Thesis"],"citation":{"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>","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>","ista":"Artner C. 2022. Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature. Institute of Science and Technology Austria.","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>.","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>.","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."},"has_accepted_license":"1","oa":1,"publication_status":"published","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"SSU"}],"ddc":["580"],"date_published":"2022-08-17T00:00:00Z","supervisor":[{"full_name":"Benková, Eva","id":"38F4F166-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8510-9739","first_name":"Eva","last_name":"Benková"}],"department":[{"_id":"GradSch"},{"_id":"EvBe"}],"publisher":"Institute of Science and Technology Austria","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","day":"17","file":[{"file_name":"ChristinaArtner_PhD_Thesis_2022.pdf","creator":"cartner","content_type":"application/pdf","embargo":"2023-09-08","relation":"main_file","file_size":11113608,"checksum":"a2c2fdc28002538840490bfa6a08b2cb","date_updated":"2023-09-09T22:30:03Z","file_id":"11907","access_level":"open_access","date_created":"2022-08-17T12:08:49Z"},{"embargo_to":"open_access","creator":"cartner","file_size":19097730,"relation":"source_file","content_type":"application/octet-stream","file_name":"ChristinaArtner_PhD_Thesis_2022.7z","access_level":"closed","date_created":"2022-08-17T12:08:59Z","checksum":"66b461c074b815fbe63481b3f46a9f43","file_id":"11908","date_updated":"2023-09-09T22:30:03Z"}],"author":[{"id":"45DF286A-F248-11E8-B48F-1D18A9856A87","full_name":"Artner, Christina","last_name":"Artner","first_name":"Christina"}],"degree_awarded":"PhD","title":"Modulation of auxin transport via ZF proteins adjust plant response to high ambient temperature","project":[{"name":"Hormonal regulation of plant adaptive responses to environmental signals","_id":"2685A872-B435-11E9-9278-68D0E5697425"}],"language":[{"iso":"eng"}],"keyword":["high ambient temperature","auxin","PINs","Zinc-Finger proteins","thermomorphogenesis","stress"],"publication_identifier":{"issn":["2663-337X"],"isbn":["978-3-99078-022-0"]},"doi":"10.15479/at:ista:11879"},{"date_published":"2022-08-23T00:00:00Z","ddc":["570"],"supervisor":[{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","last_name":"Siegert","first_name":"Sandra"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"}],"publication_status":"published","oa":1,"has_accepted_license":"1","related_material":{"record":[{"relation":"dissertation_contains","id":"11995","status":"public"}]},"citation":{"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>","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>","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>.","ista":"Schulz R. 2022. Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function. Institute of Science and Technology Austria.","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.","short":"R. Schulz, Chimeric G Protein-Coupled Receptors Mimic Distinct Signaling Pathways and Modulate Microglia Function, Institute of Science and Technology Austria, 2022."},"alternative_title":["ISTA Thesis"],"status":"public","date_created":"2022-08-23T11:33:11Z","file_date_updated":"2022-08-25T09:33:31Z","page":"133","type":"dissertation","oa_version":"Published Version","month":"08","abstract":[{"lang":"eng","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."}],"date_updated":"2023-08-03T13:02:26Z","_id":"11945","year":"2022","doi":"10.15479/at:ista:11945","publication_identifier":{"issn":["2663-337X"]},"language":[{"iso":"eng"}],"project":[{"name":"Modulating microglia through G protein-coupled receptor (GPCR) signaling","_id":"267F75D8-B435-11E9-9278-68D0E5697425"}],"title":"Chimeric G protein-coupled receptors mimic distinct signaling pathways and modulate microglia function","degree_awarded":"PhD","author":[{"orcid":"0000-0001-5297-733X","id":"4C5E7B96-F248-11E8-B48F-1D18A9856A87","full_name":"Schulz, Rouven","first_name":"Rouven","last_name":"Schulz"}],"day":"23","file":[{"relation":"main_file","content_type":"application/pdf","file_size":28079331,"creator":"rschulz","success":1,"file_name":"Thesis_Rouven_Schulz_2022_final.pdf","date_created":"2022-08-25T08:59:57Z","access_level":"open_access","date_updated":"2022-08-25T08:59:57Z","file_id":"11970","checksum":"61b1b666a210ff7cdd0e95ea75207a13"},{"creator":"rschulz","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","file_size":27226963,"file_name":"Thesis_Rouven_Schulz_2022_final.docx","access_level":"closed","date_created":"2022-08-25T09:00:11Z","checksum":"2b8f95ea1c134dbdb927b41b1dbeeeb5","date_updated":"2022-08-25T09:33:31Z","file_id":"11971"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_processing_charge":"No","publisher":"Institute of Science and Technology Austria","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","department":[{"_id":"GradSch"},{"_id":"SaSi"}]},{"publisher":"Springer Nature","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"JoCs"},{"_id":"PeJo"},{"_id":"JoDa"}],"publication":"Nature Communications","article_processing_charge":"No","ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","author":[{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav","last_name":"Ben Simon","first_name":"Yoav"},{"first_name":"Karola","last_name":"Käfer","full_name":"Käfer, Karola","id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky","first_name":"Philipp"},{"first_name":"Jozsef L","last_name":"Csicsvari","orcid":"0000-0002-5193-4036","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","full_name":"Csicsvari, Jozsef L"},{"last_name":"Danzl","first_name":"Johann G","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","first_name":"Peter M","last_name":"Jonas"}],"day":"16","file":[{"access_level":"open_access","date_created":"2022-08-26T11:51:40Z","checksum":"405936d9e4d33625d80c093c9713a91f","file_id":"11990","date_updated":"2022-08-26T11:51:40Z","creator":"dernst","file_size":5910357,"content_type":"application/pdf","relation":"main_file","file_name":"2022_NatureCommunications_BenSimon.pdf","success":1}],"title":"A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory","article_number":"4826","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600"},{"grant_number":"Z00312","name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425"}],"isi":1,"keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2041-1723"]},"doi":"10.1038/s41467-022-32559-8","quality_controlled":"1","acknowledgement":"We thank F. Marr and A. Schlögl for technical assistance, E. Kralli-Beller for manuscript editing, as well as C. Sommer and the Imaging and Optics Facility of the Institute of Science and Technology Austria (ISTA) for image analysis scripts and microscopy support. We extend our gratitude to J. Wallenschus and D. Rangel Guerrero for technical assistance acquiring single-unit data and I. Gridchyn for help with single-unit clustering. Finally, we also thank B. Suter for discussions, A. Saunders, M. Jösch, and H. Monyer for critically reading earlier versions of the manuscript, C. Petersen for sharing clearing protocols, and the Scientific Service Units of ISTA for efficient support. This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award for P.J. and I3600-B27 for J.G.D. and P.V.).","year":"2022","_id":"11951","date_updated":"2023-08-03T13:01:19Z","abstract":[{"lang":"eng","text":"The mammalian hippocampal formation (HF) plays a key role in several higher brain functions, such as spatial coding, learning and memory. Its simple circuit architecture is often viewed as a trisynaptic loop, processing input originating from the superficial layers of the entorhinal cortex (EC) and sending it back to its deeper layers. Here, we show that excitatory neurons in layer 6b of the mouse EC project to all sub-regions comprising the HF and receive input from the CA1, thalamus and claustrum. Furthermore, their output is characterized by unique slow-decaying excitatory postsynaptic currents capable of driving plateau-like potentials in their postsynaptic targets. Optogenetic inhibition of the EC-6b pathway affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs not only acquisition of new spatial memories, but also degradation of previously acquired ones. Our results provide evidence of a functional role for cortical layer 6b neurons in the adult brain."}],"month":"08","oa_version":"Published Version","type":"journal_article","volume":13,"file_date_updated":"2022-08-26T11:51:40Z","date_created":"2022-08-24T08:25:50Z","external_id":{"isi":["000841396400008"]},"status":"public","intvolume":"        13","citation":{"short":"Y. Ben Simon, K. Käfer, P. Velicky, J.L. Csicsvari, J.G. Danzl, P.M. Jonas, Nature Communications 13 (2022).","ieee":"Y. Ben Simon, K. Käfer, P. Velicky, J. L. Csicsvari, J. G. Danzl, and P. M. Jonas, “A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.","chicago":"Ben Simon, Yoav, Karola Käfer, Philipp Velicky, Jozsef L Csicsvari, Johann G Danzl, and Peter M Jonas. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-32559-8\">https://doi.org/10.1038/s41467-022-32559-8</a>.","ista":"Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. 2022. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. 13, 4826.","mla":"Ben Simon, Yoav, et al. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” <i>Nature Communications</i>, vol. 13, 4826, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-32559-8\">10.1038/s41467-022-32559-8</a>.","apa":"Ben Simon, Y., Käfer, K., Velicky, P., Csicsvari, J. L., Danzl, J. G., &#38; Jonas, P. M. (2022). A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-32559-8\">https://doi.org/10.1038/s41467-022-32559-8</a>","ama":"Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-32559-8\">10.1038/s41467-022-32559-8</a>"},"oa":1,"publication_status":"published","has_accepted_license":"1","date_published":"2022-08-16T00:00:00Z","ddc":["570"],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"SSU"}]}]
