[{"_id":"15257","scopus_import":"1","month":"03","date_created":"2024-04-02T11:35:58Z","publication_status":"published","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["38441122"]},"department":[{"_id":"JiFr"}],"volume":12,"publisher":"eLife Sciences Publications","corr_author":"1","quality_controlled":"1","pmid":1,"type":"journal_article","abstract":[{"text":"Root gravitropic bending represents a fundamental aspect of terrestrial plant physiology. Gravity is perceived by sedimentation of starch-rich plastids (statoliths) to the bottom of the central root cap cells. Following gravity perception, intercellular auxin transport is redirected downwards leading to an asymmetric auxin accumulation at the lower root side causing inhibition of cell expansion, ultimately resulting in downwards bending. How gravity-induced statoliths repositioning is translated into asymmetric auxin distribution remains unclear despite PIN auxin efflux carriers and the Negative Gravitropic Response of roots (NGR) proteins polarize along statolith sedimentation, thus providing a plausible mechanism for auxin flow redirection. In this study, using a functional NGR1-GFP construct, we visualized the NGR1 localization on the statolith surface and plasma membrane (PM) domains in close proximity to the statoliths, correlating with their movements. We determined that NGR1 binding to these PM domains is indispensable for NGR1 functionality and relies on cysteine acylation and adjacent polybasic regions as well as on lipid and sterol PM composition. Detailed timing of the early events following graviperception suggested that both NGR1 repolarization and initial auxin asymmetry precede the visible PIN3 polarization. This discrepancy motivated us to unveil a rapid, NGR-dependent translocation of PIN-activating AGCVIII kinase D6PK towards lower PMs of gravity-perceiving cells, thus providing an attractive model for rapid redirection of auxin fluxes following gravistimulation.","lang":"eng"}],"citation":{"short":"I. Kulich, J. Schmid, A. Teplova, L. Qi, J. Friml, ELife 12 (2024).","ieee":"I. Kulich, J. Schmid, A. Teplova, L. Qi, and J. Friml, “Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism,” <i>eLife</i>, vol. 12. eLife Sciences Publications, 2024.","ama":"Kulich I, Schmid J, Teplova A, Qi L, Friml J. Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism. <i>eLife</i>. 2024;12. doi:<a href=\"https://doi.org/10.7554/elife.91523\">10.7554/elife.91523</a>","apa":"Kulich, I., Schmid, J., Teplova, A., Qi, L., &#38; Friml, J. (2024). Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.91523\">https://doi.org/10.7554/elife.91523</a>","mla":"Kulich, Ivan, et al. “Rapid Translocation of NGR Proteins Driving Polarization of PIN-Activating D6 Protein Kinase during Root Gravitropism.” <i>ELife</i>, vol. 12, 91523, eLife Sciences Publications, 2024, doi:<a href=\"https://doi.org/10.7554/elife.91523\">10.7554/elife.91523</a>.","ista":"Kulich I, Schmid J, Teplova A, Qi L, Friml J. 2024. Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism. eLife. 12, 91523.","chicago":"Kulich, Ivan, Julia Schmid, Anastasiia Teplova, Linlin Qi, and Jiří Friml. “Rapid Translocation of NGR Proteins Driving Polarization of PIN-Activating D6 Protein Kinase during Root Gravitropism.” <i>ELife</i>. eLife Sciences Publications, 2024. <a href=\"https://doi.org/10.7554/elife.91523\">https://doi.org/10.7554/elife.91523</a>."},"date_updated":"2025-04-23T07:45:02Z","related_material":{"link":[{"description":"News on ISTA website","url":"https://ista.ac.at/en/news/beneath-the-surface/","relation":"press_release"}]},"title":"Rapid translocation of NGR proteins driving polarization of PIN-activating D6 protein kinase during root gravitropism","author":[{"first_name":"Ivan","full_name":"Kulich, Ivan","last_name":"Kulich","id":"57a1567c-8314-11eb-9063-c9ddc3451a54"},{"first_name":"Julia","last_name":"Schmid","full_name":"Schmid, Julia","id":"07cf4637-baaf-11ee-9227-e1de57d1d69b"},{"id":"e3736151-106c-11ec-b916-c2558e2762c6","full_name":"Teplova, Anastasiia","last_name":"Teplova","first_name":"Anastasiia"},{"id":"44B04502-A9ED-11E9-B6FC-583AE6697425","full_name":"Qi, Linlin","last_name":"Qi","orcid":"0000-0001-5187-8401","first_name":"Linlin"},{"first_name":"Jiří","id":"4159519E-F248-11E8-B48F-1D18A9856A87","full_name":"Friml, Jiří","last_name":"Friml","orcid":"0000-0002-8302-7596"}],"file_date_updated":"2024-04-03T13:18:00Z","has_accepted_license":"1","article_processing_charge":"Yes","status":"public","language":[{"iso":"eng"}],"oa_version":"Published Version","DOAJ_listed":"1","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"publication":"eLife","ddc":["580"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"call_identifier":"H2020","grant_number":"742985","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","_id":"261099A6-B435-11E9-9278-68D0E5697425"},{"_id":"26538374-B435-11E9-9278-68D0E5697425","name":"Molecular mechanisms of endocytic cargo recognition in plants","grant_number":"I03630","call_identifier":"FWF"}],"intvolume":"        12","date_published":"2024-03-05T00:00:00Z","doi":"10.7554/elife.91523","day":"05","file":[{"file_id":"15288","date_updated":"2024-04-03T13:18:00Z","relation":"main_file","checksum":"a73a84d3bf97a6d09d24308ca6dd0a0c","content_type":"application/pdf","file_size":11451904,"creator":"dernst","date_created":"2024-04-03T13:18:00Z","file_name":"2024_eLife_Kulich.pdf","success":1,"access_level":"open_access"}],"oa":1,"ec_funded":1,"acknowledgement":"The research leading to these results has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme grant agreement No 742985 and Austrian Science Fund (FWF): I3630-775 B25 to J.F. This research was also supported by the Lab Support Facility (LSF) and the Imaging and Optics Facility (IOF) of IST Austria, namely Tereza Bělinová for her help with the imaging. JS was supported by FemTECH fellowship.","year":"2024","publication_identifier":{"issn":["2050-084X"]},"article_type":"original","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"article_number":"91523"},{"file":[{"file_size":8871807,"creator":"dernst","date_created":"2024-07-16T11:50:03Z","file_name":"2024_STARProtoc_Amberg.pdf","success":1,"access_level":"open_access","file_id":"17260","date_updated":"2024-07-16T11:50:03Z","relation":"main_file","content_type":"application/pdf","checksum":"3f0ee62e04bf5a44b45b035662826e95"}],"oa":1,"doi":"10.1016/j.xpro.2023.102771","day":"15","date_published":"2024-03-15T00:00:00Z","intvolume":"         5","article_number":"102771","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"year":"2024","acknowledgement":"This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Imaging & Optics Facility (IOF) and Preclinical Facilities (PCF). N.A. received support from FWF Firnberg-Programme (T 1031). G.C. received support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411 as an ISTplus postdoctoral fellow. This work was also supported by IST Austria institutional funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro) to S.H.","publication_identifier":{"issn":["2666-1667"]},"article_type":"review","ec_funded":1,"publication":"STAR Protocols","project":[{"call_identifier":"FWF","grant_number":"T01031","_id":"268F8446-B435-11E9-9278-68D0E5697425","name":"Role of Eed in neural stem cell lineage progression"},{"grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020"},{"name":"Stem Cell Modulation in Neural Development and Regeneration/ P05-Molecular Mechanisms of Neural Stem Cell Lineage Progression","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F7805"},{"grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"oa_version":"Published Version","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"],"author":[{"orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg","full_name":"Amberg, Nicole","first_name":"Nicole"},{"id":"471195F6-F248-11E8-B48F-1D18A9856A87","full_name":"Cheung, Giselle T","last_name":"Cheung","orcid":"0000-0001-8457-2572","first_name":"Giselle T"},{"orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon"}],"title":"Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry","date_updated":"2025-04-15T08:23:06Z","language":[{"iso":"eng"}],"status":"public","has_accepted_license":"1","article_processing_charge":"Yes (in subscription journal)","file_date_updated":"2024-07-16T11:50:03Z","citation":{"short":"N. Amberg, G.T. Cheung, S. Hippenmeyer, STAR Protocols 5 (2024).","mla":"Amberg, Nicole, et al. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” <i>STAR Protocols</i>, vol. 5, no. 1, 102771, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">10.1016/j.xpro.2023.102771</a>.","ista":"Amberg N, Cheung GT, Hippenmeyer S. 2024. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols. 5(1), 102771.","chicago":"Amberg, Nicole, Giselle T Cheung, and Simon Hippenmeyer. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” <i>STAR Protocols</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">https://doi.org/10.1016/j.xpro.2023.102771</a>.","apa":"Amberg, N., Cheung, G. T., &#38; Hippenmeyer, S. (2024). Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">https://doi.org/10.1016/j.xpro.2023.102771</a>","ieee":"N. Amberg, G. T. Cheung, and S. Hippenmeyer, “Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry,” <i>STAR Protocols</i>, vol. 5, no. 1. Elsevier, 2024.","ama":"Amberg N, Cheung GT, Hippenmeyer S. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. <i>STAR Protocols</i>. 2024;5(1). doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">10.1016/j.xpro.2023.102771</a>"},"pmid":1,"abstract":[{"lang":"eng","text":"Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice and high-resolution phenotyping at the individual cell level. Here, we present a protocol for isolating MADM-labeled cells with high yield for downstream molecular analyses using fluorescence-activated cell sorting (FACS). We describe steps for generating MADM-labeled mice, perfusion, single-cell suspension, and debris removal. We then detail procedures for cell sorting by FACS and downstream analysis. This protocol is suitable for embryonic to adult mice.\r\nFor complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).1"}],"type":"journal_article","quality_controlled":"1","volume":5,"department":[{"_id":"SiHi"}],"publisher":"Elsevier","corr_author":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"publication_status":"published","date_created":"2023-12-13T11:48:05Z","external_id":{"pmid":["38070137"]},"_id":"14683","month":"03","issue":"1","scopus_import":"1"},{"date_created":"2024-02-27T07:10:11Z","publication_status":"published","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["38381485"],"isi":["001174278000001"]},"_id":"15033","scopus_import":"1","month":"02","quality_controlled":"1","type":"journal_article","pmid":1,"abstract":[{"lang":"eng","text":"The GNOM (GN) Guanine nucleotide Exchange Factor for ARF small GTPases (ARF-GEF) is among the best studied trafficking regulators in plants, playing crucial and unique developmental roles in patterning and polarity. The current models place GN at the Golgi apparatus (GA), where it mediates secretion/recycling, and at the plasma membrane (PM) presumably contributing to clathrin-mediated endocytosis (CME). The mechanistic basis of the developmental function of GN, distinct from the other ARF-GEFs including its closest homologue GNOM-LIKE1 (GNL1), remains elusive. Insights from this study largely extend the current notions of GN function. We show that GN, but not GNL1, localizes to the cell periphery at long-lived structures distinct from clathrin-coated pits, while CME and secretion proceed normally in <jats:italic>gn</jats:italic> knockouts. The functional GN mutant variant GN<jats:sup>fewerroots</jats:sup>, absent from the GA, suggests that the cell periphery is the major site of GN action responsible for its developmental function. Following inhibition by Brefeldin A, GN, but not GNL1, relocates to the PM likely on exocytic vesicles, suggesting selective molecular associations en route to the cell periphery. A study of GN-GNL1 chimeric ARF-GEFs indicates that all GN domains contribute to the specific GN function in a partially redundant manner. Together, this study offers significant steps toward the elucidation of the mechanism underlying unique cellular and development functions of GNOM."}],"citation":{"short":"M. Adamowski, I. Matijevic, J. Friml, ELife 13 (2024).","ista":"Adamowski M, Matijevic I, Friml J. 2024. Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. eLife. 13.","chicago":"Adamowski, Maciek, Ivana Matijevic, and Jiří Friml. “Developmental Patterning Function of GNOM ARF-GEF Mediated from the Cell Periphery.” <i>ELife</i>. eLife Sciences Publications, 2024. <a href=\"https://doi.org/10.7554/elife.68993\">https://doi.org/10.7554/elife.68993</a>.","mla":"Adamowski, Maciek, et al. “Developmental Patterning Function of GNOM ARF-GEF Mediated from the Cell Periphery.” <i>ELife</i>, vol. 13, eLife Sciences Publications, 2024, doi:<a href=\"https://doi.org/10.7554/elife.68993\">10.7554/elife.68993</a>.","apa":"Adamowski, M., Matijevic, I., &#38; Friml, J. (2024). Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.68993\">https://doi.org/10.7554/elife.68993</a>","ieee":"M. Adamowski, I. Matijevic, and J. Friml, “Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery,” <i>eLife</i>, vol. 13. eLife Sciences Publications, 2024.","ama":"Adamowski M, Matijevic I, Friml J. Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. <i>eLife</i>. 2024;13. doi:<a href=\"https://doi.org/10.7554/elife.68993\">10.7554/elife.68993</a>"},"OA_type":"gold","department":[{"_id":"JiFr"}],"volume":13,"publisher":"eLife Sciences Publications","corr_author":"1","oa_version":"Published Version","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"DOAJ_listed":"1","APC_amount":"2792,52 EUR","date_updated":"2025-10-15T06:31:47Z","title":"Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery","author":[{"orcid":"0000-0001-6463-5257","full_name":"Adamowski, Maciek","last_name":"Adamowski","id":"45F536D2-F248-11E8-B48F-1D18A9856A87","first_name":"Maciek"},{"id":"83c17ce3-15b2-11ec-abd3-f486545870bd","full_name":"Matijevic, Ivana","last_name":"Matijevic","first_name":"Ivana"},{"first_name":"Jiří","orcid":"0000-0002-8302-7596","id":"4159519E-F248-11E8-B48F-1D18A9856A87","last_name":"Friml","full_name":"Friml, Jiří"}],"file_date_updated":"2024-07-22T11:51:50Z","article_processing_charge":"Yes","has_accepted_license":"1","language":[{"iso":"eng"}],"status":"public","intvolume":"        13","date_published":"2024-02-21T00:00:00Z","doi":"10.7554/elife.68993","day":"21","oa":1,"file":[{"date_updated":"2024-07-22T11:51:50Z","file_id":"17310","checksum":"b2b2d583b433823af731842f1420113e","content_type":"application/pdf","relation":"main_file","creator":"dernst","file_size":15675744,"file_name":"2024_eLife_Adamowski.pdf","success":1,"date_created":"2024-07-22T11:51:50Z","access_level":"open_access"}],"ec_funded":1,"article_type":"original","acknowledgement":"The authors would like to gratefully acknowledge Dr Xixi Zhang for cloning the GNL1/pDONR221 construct and for useful discussions.H2020 European Research Council Advanced Grant ETAP742985 to Jiří Friml, Austrian Science Fund I 3630-B25 to Jiří Friml","year":"2024","publication_identifier":{"issn":["2050-084X"]},"publication":"eLife","isi":1,"ddc":["580"],"OA_place":"publisher","project":[{"call_identifier":"H2020","grant_number":"742985","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","_id":"261099A6-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","grant_number":"I03630","name":"Molecular mechanisms of endocytic cargo recognition in plants","_id":"26538374-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","_id":"3AC91DDA-15DF-11EA-824D-93A3E7B544D1","name":"FWF Open Access Fund"}],"user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345"},{"keyword":["General Medicine","Immunology"],"oa_version":"Published Version","language":[{"iso":"eng"}],"status":"public","article_processing_charge":"No","title":"CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration","author":[{"first_name":"Jonna H","id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87","last_name":"Alanko","full_name":"Alanko, Jonna H","orcid":"0000-0002-7698-3061"},{"first_name":"Mehmet C","id":"50B2A802-6007-11E9-A42B-EB23E6697425","last_name":"Ucar","full_name":"Ucar, Mehmet C","orcid":"0000-0003-0506-4217"},{"last_name":"Canigova","full_name":"Canigova, Nikola","id":"3795523E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8518-5926","first_name":"Nikola"},{"last_name":"Stopp","full_name":"Stopp, Julian A","id":"489E3F00-F248-11E8-B48F-1D18A9856A87","first_name":"Julian A"},{"full_name":"Schwarz, Jan","last_name":"Schwarz","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87","first_name":"Jan"},{"orcid":"0000-0001-5145-4609","id":"4515C308-F248-11E8-B48F-1D18A9856A87","last_name":"Merrin","full_name":"Merrin, Jack","first_name":"Jack"},{"first_name":"Edouard B","orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","last_name":"Sixt"}],"related_material":{"record":[{"status":"public","relation":"research_data","id":"14279"},{"id":"19745","relation":"dissertation_contains","status":"public"},{"status":"public","id":"14697","relation":"dissertation_contains"}]},"date_updated":"2026-05-14T22:30:31Z","article_number":"adc9584","ec_funded":1,"article_type":"original","year":"2023","acknowledgement":"We thank I. de Vries and the Scientific Service Units (Life Sciences, Bioimaging, Nanofabrication, Preclinical and Miba Machine Shop) of the Institute of Science and Technology Austria for excellent support, as well as all the rotation students assisting in the laboratory work (B. Zens, H. Schön, and D. Babic).\r\nThis work was supported by grants from the European Research Council under the European Union’s Horizon 2020 research to M.S. (grant agreement no. 724373) and to E.H. (grant agreement no. 851288), and a grant by the Austrian Science Fund (DK Nanocell W1250-B20) to M.S. J.A. was supported by the Jenny and Antti Wihuri Foundation and Research Council of Finland's Flagship Programme InFLAMES (decision number: 357910). M.C.U. was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411.","publication_identifier":{"issn":["2470-9468"]},"day":"01","doi":"10.1126/sciimmunol.adc9584","oa":1,"intvolume":"         8","date_published":"2023-09-01T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"call_identifier":"H2020","name":"Cellular Navigation Along Spatial Gradients","_id":"25FE9508-B435-11E9-9278-68D0E5697425","grant_number":"724373"},{"call_identifier":"H2020","_id":"05943252-7A3F-11EA-A408-12923DDC885E","name":"Design Principles of Branching Morphogenesis","grant_number":"851288"},{"call_identifier":"FWF","_id":"265E2996-B435-11E9-9278-68D0E5697425","name":"Nano-Analytics of Cellular Systems","grant_number":"W01250-B20"},{"grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"publication":"Science Immunology","isi":1,"external_id":{"pmid":["37656776"],"isi":["001062110600003"]},"publication_status":"published","date_created":"2023-09-06T08:07:51Z","month":"09","issue":"87","scopus_import":"1","_id":"14274","pmid":1,"abstract":[{"lang":"eng","text":"Immune responses rely on the rapid and coordinated migration of leukocytes. Whereas it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how these gradients are generated, maintained, and modulated. By combining experimental data with theory on leukocyte chemotaxis guided by the G protein–coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and a modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, dynamically shaping the spatiotemporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, and provide a guidance cue for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization."}],"type":"journal_article","citation":{"apa":"Alanko, J. H., Ucar, M. C., Canigova, N., Stopp, J. A., Schwarz, J., Merrin, J., … Sixt, M. K. (2023). CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. <i>Science Immunology</i>. American Association for the Advancement of Science. <a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">https://doi.org/10.1126/sciimmunol.adc9584</a>","ieee":"J. H. Alanko <i>et al.</i>, “CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration,” <i>Science Immunology</i>, vol. 8, no. 87. American Association for the Advancement of Science, 2023.","ama":"Alanko JH, Ucar MC, Canigova N, et al. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. <i>Science Immunology</i>. 2023;8(87). doi:<a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">10.1126/sciimmunol.adc9584</a>","ista":"Alanko JH, Ucar MC, Canigova N, Stopp JA, Schwarz J, Merrin J, Hannezo EB, Sixt MK. 2023. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. Science Immunology. 8(87), adc9584.","chicago":"Alanko, Jonna H, Mehmet C Ucar, Nikola Canigova, Julian A Stopp, Jan Schwarz, Jack Merrin, Edouard B Hannezo, and Michael K Sixt. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” <i>Science Immunology</i>. American Association for the Advancement of Science, 2023. <a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">https://doi.org/10.1126/sciimmunol.adc9584</a>.","mla":"Alanko, Jonna H., et al. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” <i>Science Immunology</i>, vol. 8, no. 87, adc9584, American Association for the Advancement of Science, 2023, doi:<a href=\"https://doi.org/10.1126/sciimmunol.adc9584\">10.1126/sciimmunol.adc9584</a>.","short":"J.H. Alanko, M.C. Ucar, N. Canigova, J.A. Stopp, J. Schwarz, J. Merrin, E.B. Hannezo, M.K. Sixt, Science Immunology 8 (2023)."},"quality_controlled":"1","corr_author":"1","publisher":"American Association for the Advancement of Science","main_file_link":[{"url":"https://doi.org/10.1126/sciimmunol.adc9584","open_access":"1"}],"volume":8,"department":[{"_id":"MiSi"},{"_id":"EdHa"},{"_id":"NanoFab"}]},{"_id":"12117","scopus_import":"1","issue":"4","month":"12","date_created":"2023-01-12T11:56:38Z","publication_status":"published","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","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"},"external_id":{"pmid":["36595902"]},"department":[{"_id":"SaSi"},{"_id":"GradSch"}],"volume":3,"publisher":"Elsevier","corr_author":"1","quality_controlled":"1","pmid":1,"type":"journal_article","abstract":[{"text":"To understand how potential gene manipulations affect in vitro microglia, we provide a set of short protocols to evaluate microglia identity and function. We detail steps for immunostaining to determine microglia identity. We describe three functional assays for microglia: phagocytosis, calcium response following ATP stimulation, and cytokine expression upon inflammatory stimuli. We apply these protocols to human induced-pluripotent-stem-cell (hiPSC)-derived microglia, but they can be also applied to other in vitro microglial models including primary mouse microglia.\r\nFor complete details on the use and execution of this protocol, please refer to Bartalska et al. (2022).1","lang":"eng"}],"citation":{"ama":"Hübschmann V, Korkut M, Siegert S. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. <i>STAR Protocols</i>. 2022;3(4). doi:<a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">10.1016/j.xpro.2022.101866</a>","apa":"Hübschmann, V., Korkut, M., &#38; Siegert, S. (2022). Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">https://doi.org/10.1016/j.xpro.2022.101866</a>","ieee":"V. Hübschmann, M. Korkut, and S. Siegert, “Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay,” <i>STAR Protocols</i>, vol. 3, no. 4. Elsevier, 2022.","ista":"Hübschmann V, Korkut M, Siegert S. 2022. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. 3(4), 101866.","chicago":"Hübschmann, Verena, Medina Korkut, and Sandra Siegert. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” <i>STAR Protocols</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">https://doi.org/10.1016/j.xpro.2022.101866</a>.","mla":"Hübschmann, Verena, et al. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” <i>STAR Protocols</i>, vol. 3, no. 4, 101866, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.xpro.2022.101866\">10.1016/j.xpro.2022.101866</a>.","short":"V. Hübschmann, M. Korkut, S. Siegert, STAR Protocols 3 (2022)."},"related_material":{"record":[{"status":"public","relation":"other","id":"11478"}]},"date_updated":"2025-06-11T13:58:47Z","title":"Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay","author":[{"first_name":"Verena","full_name":"Hübschmann, Verena","last_name":"Hübschmann","id":"32B7C918-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-4309-2251","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87","full_name":"Korkut, Medina","last_name":"Korkut","first_name":"Medina"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","first_name":"Sandra"}],"file_date_updated":"2023-01-23T09:50:51Z","article_processing_charge":"No","has_accepted_license":"1","status":"public","language":[{"iso":"eng"}],"oa_version":"Published Version","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"],"publication":"STAR Protocols","ddc":["570"],"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"_id":"25D4A630-B435-11E9-9278-68D0E5697425","name":"Microglia action towards neuronal circuit formation and function in health and disease","grant_number":"715571","call_identifier":"H2020"},{"grant_number":"SC19-017","_id":"9B99D380-BA93-11EA-9121-9846C619BF3A","name":"How human microglia shape developing neurons during health and inflammation"}],"intvolume":"         3","date_published":"2022-12-16T00:00:00Z","day":"16","doi":"10.1016/j.xpro.2022.101866","oa":1,"file":[{"date_updated":"2023-01-23T09:50:51Z","file_id":"12340","checksum":"3c71b8a60633d42c2f77c49025d5559b","content_type":"application/pdf","relation":"main_file","creator":"dernst","file_size":6251945,"date_created":"2023-01-23T09:50:51Z","success":1,"file_name":"2022_STARProtocols_Huebschmann.pdf","access_level":"open_access"}],"ec_funded":1,"publication_identifier":{"issn":["2666-1667"]},"article_type":"letter_note","year":"2022","acknowledgement":"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.). We thank Rouven Schulz and Alessandro Venturino for their insights into functional assays and data analysis, Verena Seiboth for insights into necessary institutional permission, and ISTA imaging & optics facility (IOF) especially Bernhard Hochreiter for their support.","acknowledged_ssus":[{"_id":"Bio"}],"article_number":"101866"},{"quality_controlled":"1","citation":{"short":"T. Petzold, Z. Zhang, I. Ballesteros, I. Saleh, A. Polzin, M. Thienel, L. Liu, Q. Ul Ain, V. Ehreiser, C. Weber, B. Kilani, P. Mertsch, J. Götschke, S. Cremer, W. Fu, M. Lorenz, H. Ishikawa-Ankerhold, E. Raatz, S. El-Nemr, A. Görlach, E. Marhuenda, K. Stark, J. Pircher, D. Stegner, C. Gieger, M. Schmidt-Supprian, F.R. Gärtner, I. Almendros, M. Kelm, C. Schulz, A. Hidalgo, S. Massberg, Immunity 55 (2022) 2285–2299.e7.","mla":"Petzold, Tobias, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives Platelet Production and Boosts Cardiovascular Disease.” <i>Immunity</i>, vol. 55, no. 12, Elsevier, 2022, p. 2285–2299.e7, doi:<a href=\"https://doi.org/10.1016/j.immuni.2022.10.001\">10.1016/j.immuni.2022.10.001</a>.","ista":"Petzold T, Zhang Z, Ballesteros I, Saleh I, Polzin A, Thienel M, Liu L, Ul Ain Q, Ehreiser V, Weber C, Kilani B, Mertsch P, Götschke J, Cremer S, Fu W, Lorenz M, Ishikawa-Ankerhold H, Raatz E, El-Nemr S, Görlach A, Marhuenda E, Stark K, Pircher J, Stegner D, Gieger C, Schmidt-Supprian M, Gärtner FR, Almendros I, Kelm M, Schulz C, Hidalgo A, Massberg S. 2022. Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. 55(12), 2285–2299.e7.","chicago":"Petzold, Tobias, Zhe Zhang, Iván Ballesteros, Inas Saleh, Amin Polzin, Manuela Thienel, Lulu Liu, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives Platelet Production and Boosts Cardiovascular Disease.” <i>Immunity</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.immuni.2022.10.001\">https://doi.org/10.1016/j.immuni.2022.10.001</a>.","apa":"Petzold, T., Zhang, Z., Ballesteros, I., Saleh, I., Polzin, A., Thienel, M., … Massberg, S. (2022). Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. <i>Immunity</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.immuni.2022.10.001\">https://doi.org/10.1016/j.immuni.2022.10.001</a>","ieee":"T. Petzold <i>et al.</i>, “Neutrophil ‘plucking’ on megakaryocytes drives platelet production and boosts cardiovascular disease,” <i>Immunity</i>, vol. 55, no. 12. Elsevier, p. 2285–2299.e7, 2022.","ama":"Petzold T, Zhang Z, Ballesteros I, et al. Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. <i>Immunity</i>. 2022;55(12):2285-2299.e7. doi:<a href=\"https://doi.org/10.1016/j.immuni.2022.10.001\">10.1016/j.immuni.2022.10.001</a>"},"pmid":1,"type":"journal_article","abstract":[{"lang":"eng","text":"Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil and platelet lineages extends to the earliest stages of platelet formation by megakaryocytes in the bone marrow. Using intravital microscopy, we show that neutrophils “plucked” intravascular megakaryocyte extensions, termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal megakaryocytes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated kinase activation through reactive oxygen species. By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of platelets in steady state. Following myocardial infarction, plucking neutrophils drove excessive release of young, reticulated platelets and boosted the risk of recurrent ischemia. Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent thrombosis after myocardial infarction and thrombus burden in venous thrombosis. We establish neutrophil plucking as a target to reduce thromboischemic events."}],"publisher":"Elsevier","department":[{"_id":"MiSi"}],"volume":55,"external_id":{"pmid":["36272416"],"isi":["000922019600003"]},"date_created":"2023-01-12T11:56:54Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","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"},"publication_status":"published","issue":"12","scopus_import":"1","month":"12","_id":"12119","year":"2022","article_type":"original","publication_identifier":{"issn":["1074-7613"]},"acknowledgement":"We thank Coung Kieu and Dominik van den Heuvel for excellent technical assistance. This work was supported by the German Research Foundation (PE2704/2-1, PE2704/3-1 to T.P., SFB 1123-project B06 to S.M., SFB1525 project A07 to D.S, TRR 332 project A7 to C.S., PO 2247/2-1 to A.P., SFB1116-project B11 to A.P. and B12 to M.K.), LMU Munich’s Institutional\r\nStrategy LMUexcellent within the framework of the German Excellence Initiative (No. 806 32 006 to T.P.), and by the German Centre for Cardiovascular Research (DZHK) to T.P. (Postdoc Start-up grant No. 100378833). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 833440 to S.M.). F.G. received funding from the European Union’s\r\nHorizon 2020 research and innovation program under the Marie Sk1odowska-Curie grant agreement no. 747687. A.H. was funded by RTI2018-095497-B-I00 from Ministerio de Ciencia e Innovacio´ n (MICINN), HR17_00527 from Fundacion La Caixa, and Transatlantic Network of Excellence (TNE-18CVD04) from the Leducq Foundation. The CNIC is supported by the MICINN and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). A.P. was supported by the Forschungskommission of the Medical Faculty of the Heinrich-Heine-Universität Düsseldorf (No. 18-2019 to A.P.). C.G. was supported by the Helmholtz Alliance ‘Aging and Metabolic Programming, AMPro,’ by the German Federal\r\nMinistry of Education and Research to the German Center for Diabetes Research (DZD), and by the Bavarian State Ministry of Health and Care through the research project DigiMed Bayern.","ec_funded":1,"date_published":"2022-12-13T00:00:00Z","intvolume":"        55","file":[{"date_updated":"2023-01-23T10:18:48Z","file_id":"12341","content_type":"application/pdf","checksum":"073267a9c0ad9f85a650053bc7b23777","relation":"main_file","creator":"dernst","file_size":5299475,"success":1,"date_created":"2023-01-23T10:18:48Z","file_name":"2022_Immunity_Petzold.pdf","access_level":"open_access"}],"oa":1,"day":"13","doi":"10.1016/j.immuni.2022.10.001","ddc":["570"],"project":[{"_id":"260AA4E2-B435-11E9-9278-68D0E5697425","name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","grant_number":"747687","call_identifier":"H2020"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","isi":1,"publication":"Immunity","keyword":["Infectious Diseases","Immunology","Immunology and Allergy"],"oa_version":"Published Version","article_processing_charge":"No","has_accepted_license":"1","file_date_updated":"2023-01-23T10:18:48Z","language":[{"iso":"eng"}],"status":"public","page":"2285-2299.e7","date_updated":"2025-04-14T07:43:16Z","title":"Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease","author":[{"first_name":"Tobias","full_name":"Petzold, Tobias","last_name":"Petzold"},{"first_name":"Zhe","full_name":"Zhang, Zhe","last_name":"Zhang"},{"last_name":"Ballesteros","full_name":"Ballesteros, Iván","first_name":"Iván"},{"full_name":"Saleh, Inas","last_name":"Saleh","first_name":"Inas"},{"first_name":"Amin","last_name":"Polzin","full_name":"Polzin, Amin"},{"first_name":"Manuela","last_name":"Thienel","full_name":"Thienel, Manuela"},{"first_name":"Lulu","full_name":"Liu, Lulu","last_name":"Liu"},{"first_name":"Qurrat","full_name":"Ul Ain, Qurrat","last_name":"Ul Ain"},{"full_name":"Ehreiser, Vincent","last_name":"Ehreiser","first_name":"Vincent"},{"first_name":"Christian","last_name":"Weber","full_name":"Weber, Christian"},{"full_name":"Kilani, Badr","last_name":"Kilani","first_name":"Badr"},{"full_name":"Mertsch, Pontus","last_name":"Mertsch","first_name":"Pontus"},{"last_name":"Götschke","full_name":"Götschke, Jeremias","first_name":"Jeremias"},{"last_name":"Cremer","full_name":"Cremer, Sophie","first_name":"Sophie"},{"first_name":"Wenwen","last_name":"Fu","full_name":"Fu, Wenwen"},{"first_name":"Michael","last_name":"Lorenz","full_name":"Lorenz, Michael"},{"last_name":"Ishikawa-Ankerhold","full_name":"Ishikawa-Ankerhold, Hellen","first_name":"Hellen"},{"first_name":"Elisabeth","last_name":"Raatz","full_name":"Raatz, Elisabeth"},{"first_name":"Shaza","full_name":"El-Nemr, Shaza","last_name":"El-Nemr"},{"first_name":"Agnes","full_name":"Görlach, Agnes","last_name":"Görlach"},{"first_name":"Esther","last_name":"Marhuenda","full_name":"Marhuenda, Esther"},{"full_name":"Stark, Konstantin","last_name":"Stark","first_name":"Konstantin"},{"first_name":"Joachim","full_name":"Pircher, Joachim","last_name":"Pircher"},{"full_name":"Stegner, David","last_name":"Stegner","first_name":"David"},{"first_name":"Christian","full_name":"Gieger, Christian","last_name":"Gieger"},{"last_name":"Schmidt-Supprian","full_name":"Schmidt-Supprian, Marc","first_name":"Marc"},{"first_name":"Florian R","id":"397A88EE-F248-11E8-B48F-1D18A9856A87","full_name":"Gärtner, Florian R","last_name":"Gärtner","orcid":"0000-0001-6120-3723"},{"full_name":"Almendros, Isaac","last_name":"Almendros","first_name":"Isaac"},{"first_name":"Malte","full_name":"Kelm, Malte","last_name":"Kelm"},{"last_name":"Schulz","full_name":"Schulz, Christian","first_name":"Christian"},{"last_name":"Hidalgo","full_name":"Hidalgo, Andrés","first_name":"Andrés"},{"first_name":"Steffen","full_name":"Massberg, Steffen","last_name":"Massberg"}]},{"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"publication_status":"published","date_created":"2023-01-12T12:02:54Z","external_id":{"isi":["000884278600004"],"pmid":["36379998"]},"_id":"12131","month":"11","scopus_import":"1","citation":{"chicago":"Byazrova, Maria G., Ekaterina A. Astakhova, Aygul Minnegalieva, Maria M. Sukhova, Artem A. Mikhailov, Alexey G. Prilipov, Andrey A. Gorchakov, and Alexander V. Filatov. “Anti-Ad26 Humoral Immunity Does Not Compromise SARS-COV-2 Neutralizing Antibody Responses Following Gam-COVID-Vac Booster Vaccination.” <i>Npj Vaccines</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41541-022-00566-x\">https://doi.org/10.1038/s41541-022-00566-x</a>.","ista":"Byazrova MG, Astakhova EA, Minnegalieva A, Sukhova MM, Mikhailov AA, Prilipov AG, Gorchakov AA, Filatov AV. 2022. Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination. npj Vaccines. 7, 145.","mla":"Byazrova, Maria G., et al. “Anti-Ad26 Humoral Immunity Does Not Compromise SARS-COV-2 Neutralizing Antibody Responses Following Gam-COVID-Vac Booster Vaccination.” <i>Npj Vaccines</i>, vol. 7, 145, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41541-022-00566-x\">10.1038/s41541-022-00566-x</a>.","apa":"Byazrova, M. G., Astakhova, E. A., Minnegalieva, A., Sukhova, M. M., Mikhailov, A. A., Prilipov, A. G., … Filatov, A. V. (2022). Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination. <i>Npj Vaccines</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41541-022-00566-x\">https://doi.org/10.1038/s41541-022-00566-x</a>","ama":"Byazrova MG, Astakhova EA, Minnegalieva A, et al. Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination. <i>npj Vaccines</i>. 2022;7. doi:<a href=\"https://doi.org/10.1038/s41541-022-00566-x\">10.1038/s41541-022-00566-x</a>","ieee":"M. G. Byazrova <i>et al.</i>, “Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination,” <i>npj Vaccines</i>, vol. 7. Springer Nature, 2022.","short":"M.G. Byazrova, E.A. Astakhova, A. Minnegalieva, M.M. Sukhova, A.A. Mikhailov, A.G. Prilipov, A.A. Gorchakov, A.V. Filatov, Npj Vaccines 7 (2022)."},"type":"journal_article","abstract":[{"lang":"eng","text":"Replication-incompetent adenoviral vectors have been extensively used as a platform for vaccine design, with at least four anti-COVID-19 vaccines authorized to date. These vaccines elicit neutralizing antibody responses directed against SARS-CoV-2 Spike protein and confer significant level of protection against SARS-CoV-2 infection. Immunization with adenovirus-vectored vaccines is known to be accompanied by the production of anti-vector antibodies, which may translate into reduced efficacy of booster or repeated rounds of revaccination. Here, we used blood samples from patients who received an adenovirus-based Gam-COVID-Vac vaccine to address the question of whether anti-vector antibodies may influence the magnitude of SARS-CoV-2-specific humoral response after booster vaccination. We observed that rAd26-based prime vaccination with Gam-COVID-Vac induced the development of Ad26-neutralizing antibodies, which persisted in circulation for at least 9 months. Our analysis further indicates that high pre-boost Ad26 neutralizing antibody titers do not appear to affect the humoral immunogenicity of the Gam-COVID-Vac boost. The titers of anti-SARS-CoV-2 RBD IgGs and antibodies, which neutralized both the wild type and the circulating variants of concern of SARS-CoV-2 such as Delta and Omicron, were independent of the pre-boost levels of Ad26-neutralizing antibodies. Thus, our results support the development of repeated immunization schedule with adenovirus-based COVID-19 vaccines."}],"pmid":1,"quality_controlled":"1","volume":7,"department":[{"_id":"FyKo"}],"publisher":"Springer Nature","oa_version":"Published Version","keyword":["Pharmacology (medical)","Infectious Diseases","Pharmacology","Immunology","SARS-COV-2","COVID"],"author":[{"first_name":"Maria G.","full_name":"Byazrova, Maria G.","last_name":"Byazrova"},{"first_name":"Ekaterina A.","full_name":"Astakhova, Ekaterina A.","last_name":"Astakhova"},{"id":"87DF77F0-1D9A-11EA-B6AE-CE443DDC885E","last_name":"Minnegalieva","full_name":"Minnegalieva, Aygul","first_name":"Aygul"},{"last_name":"Sukhova","full_name":"Sukhova, Maria M.","first_name":"Maria M."},{"first_name":"Artem A.","full_name":"Mikhailov, Artem A.","last_name":"Mikhailov"},{"last_name":"Prilipov","full_name":"Prilipov, Alexey G.","first_name":"Alexey G."},{"last_name":"Gorchakov","full_name":"Gorchakov, Andrey A.","first_name":"Andrey A."},{"full_name":"Filatov, Alexander V.","last_name":"Filatov","first_name":"Alexander V."}],"title":"Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination","date_updated":"2023-08-04T08:52:40Z","status":"public","language":[{"iso":"eng"}],"article_processing_charge":"No","has_accepted_license":"1","file_date_updated":"2023-01-23T11:22:09Z","oa":1,"file":[{"access_level":"open_access","file_size":1856046,"creator":"dernst","file_name":"2022_njpVaccines_Byazrova.pdf","success":1,"date_created":"2023-01-23T11:22:09Z","relation":"main_file","content_type":"application/pdf","checksum":"ddaac096381565b2b4b7dcc34cdbc4ee","file_id":"12347","date_updated":"2023-01-23T11:22:09Z"}],"doi":"10.1038/s41541-022-00566-x","day":"15","date_published":"2022-11-15T00:00:00Z","intvolume":"         7","article_number":"145","acknowledgement":"We thank Sergey Kulemzin, Grigory Efimov, Yuri Lebedin, Alexander Taranin and Rudolf Valenta for providing reagents. Figures were created with the help of BioRender.com. This work was supported by the Russian Science Foundation (Project 21-15-00286). Byazrova M.G. was supported by the RUDN University Strategic Academic Leadership Program.","publication_identifier":{"issn":["2059-0105"]},"article_type":"original","year":"2022","isi":1,"publication":"npj Vaccines","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"]},{"_id":"12157","scopus_import":"1","month":"09","date_created":"2023-01-12T12:09:00Z","publication_status":"published","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000890735600001"]},"department":[{"_id":"NiBa"}],"volume":11,"corr_author":"1","publisher":"eLife Sciences Publications","quality_controlled":"1","abstract":[{"lang":"eng","text":"Polygenic adaptation is thought to be ubiquitous, yet remains poorly understood. Here, we model this process analytically, in the plausible setting of a highly polygenic, quantitative trait that experiences a sudden shift in the fitness optimum. We show how the mean phenotype changes over time, depending on the effect sizes of loci that contribute to variance in the trait, and characterize the allele dynamics at these loci. Notably, we describe the two phases of the allele dynamics: The first is a rapid phase, in which directional selection introduces small frequency differences between alleles whose effects are aligned with or opposed to the shift, ultimately leading to small differences in their probability of fixation during a second, longer phase, governed by stabilizing selection. As we discuss, key results should hold in more general settings and have important implications for efforts to identify the genetic basis of adaptation in humans and other species."}],"type":"journal_article","citation":{"mla":"Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change in Environment.” <i>ELife</i>, vol. 11, 66697, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.66697\">10.7554/elife.66697</a>.","chicago":"Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change in Environment.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.66697\">https://doi.org/10.7554/elife.66697</a>.","ista":"Hayward L, Sella G. 2022. Polygenic adaptation after a sudden change in environment. eLife. 11, 66697.","apa":"Hayward, L., &#38; Sella, G. (2022). Polygenic adaptation after a sudden change in environment. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.66697\">https://doi.org/10.7554/elife.66697</a>","ieee":"L. Hayward and G. Sella, “Polygenic adaptation after a sudden change in environment,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","ama":"Hayward L, Sella G. Polygenic adaptation after a sudden change in environment. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.66697\">10.7554/elife.66697</a>","short":"L. Hayward, G. Sella, ELife 11 (2022)."},"date_updated":"2024-10-09T21:03:38Z","title":"Polygenic adaptation after a sudden change in environment","author":[{"id":"fc885ee5-24bf-11eb-ad7b-bcc5104c0c1b","last_name":"Hayward","full_name":"Hayward, Laura","first_name":"Laura"},{"last_name":"Sella","full_name":"Sella, Guy","first_name":"Guy"}],"file_date_updated":"2023-01-24T12:21:32Z","has_accepted_license":"1","article_processing_charge":"No","status":"public","language":[{"iso":"eng"}],"oa_version":"Published Version","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"publication":"eLife","isi":1,"ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":"        11","date_published":"2022-09-26T00:00:00Z","day":"26","doi":"10.7554/elife.66697","oa":1,"file":[{"access_level":"open_access","file_name":"2022_eLife_Hayward.pdf","date_created":"2023-01-24T12:21:32Z","success":1,"creator":"dernst","file_size":18935612,"checksum":"28de155b231ac1c8d4501c98b2fb359a","content_type":"application/pdf","relation":"main_file","date_updated":"2023-01-24T12:21:32Z","file_id":"12363"}],"year":"2022","article_type":"original","publication_identifier":{"eissn":["2050-084X"]},"acknowledgement":"We thank Guy Amster, Jeremy Berg, Nick Barton, Yuval Simons and Molly Przeworski for many helpful discussions, and Jeremy Berg, Graham Coop, Joachim Hermisson, Guillaume Martin, Will Milligan, Peter Ralph, Yuval Simons, Leo Speidel and Molly Przeworski for comments on the manuscript.\r\nNational Institutes of Health GM115889 Laura Katharine Hayward Guy Sella \r\nNational Institutes of Health GM121372 Laura Katharine Hayward","article_number":"66697"},{"article_number":"965446","publication_identifier":{"issn":["1664-3224"]},"year":"2022","article_type":"original","acknowledgement":"The authors declare that this study received funding from Immunofusion. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.","day":"16","doi":"10.3389/fimmu.2022.965446","oa":1,"file":[{"file_id":"12443","date_updated":"2023-01-30T09:22:26Z","relation":"main_file","checksum":"f8f5d8110710033d0532e7e08bf9dad4","content_type":"application/pdf","file_name":"2022_FrontiersImmunology_Dormeshkin.pdf","date_created":"2023-01-30T09:22:26Z","success":1,"file_size":5695892,"creator":"dernst","access_level":"open_access"}],"intvolume":"        13","date_published":"2022-09-16T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"publication":"Frontiers in Immunology","isi":1,"keyword":["Immunology","Immunology and Allergy","COVID-19","SARS-CoV-2","synthetic library","RBD","neutralization nanobody","VHH"],"oa_version":"Published Version","language":[{"iso":"eng"}],"status":"public","file_date_updated":"2023-01-30T09:22:26Z","article_processing_charge":"No","has_accepted_license":"1","title":"Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library","author":[{"last_name":"Dormeshkin","full_name":"Dormeshkin, Dmitri","first_name":"Dmitri"},{"first_name":"Michail","full_name":"Shapira, Michail","last_name":"Shapira"},{"first_name":"Simon","last_name":"Dubovik","full_name":"Dubovik, Simon"},{"id":"4968f7ad-eb97-11eb-a6c2-8ed382e8912c","full_name":"Kavaleuski, Anton","last_name":"Kavaleuski","orcid":"0000-0003-2091-526X","first_name":"Anton"},{"first_name":"Mikalai","full_name":"Katsin, Mikalai","last_name":"Katsin"},{"last_name":"Migas","full_name":"Migas, Alexandr","first_name":"Alexandr"},{"first_name":"Alexander","full_name":"Meleshko, Alexander","last_name":"Meleshko"},{"first_name":"Sergei","full_name":"Semyonov, Sergei","last_name":"Semyonov"}],"date_updated":"2025-06-11T13:42:26Z","pmid":1,"abstract":[{"text":"The COVID−19 pandemic not only resulted in a global crisis, but also accelerated vaccine development and antibody discovery. Herein we report a synthetic humanized VHH library development pipeline for nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) isolation. Trinucleotide-based randomization of CDRs by Kunkel mutagenesis with the subsequent rolling-cycle amplification resulted in more than 10<jats:sup>11</jats:sup> diverse phage display library in a manageable for a single person number of electroporation reactions. We identified a number of nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) by screening a novel synthetic humanized antibody library. In order to explore the most robust and fast method for affinity improvement, we performed affinity maturation by CDR1 and CDR2 shuffling and avidity engineering by multivalent trimeric VHH fusion protein construction. As a result, H7-Fc and G12x3-Fc binders were developed with the affinities in nM and pM range respectively. Importantly, these affinities are weakly influenced by most of SARS-CoV-2 VoC mutations and they retain moderate binding to BA.4\\5. The plaque reduction neutralization test (PRNT) resulted in IC50 = 100 ng\\ml and 9.6 ng\\ml for H7-Fc and G12x3-Fc antibodies, respectively, for the emerging Omicron BA.1 variant. Therefore, these VHH could expand the present landscape of SARS-CoV-2 neutralization binders with the therapeutic potential for present and future SARS-CoV-2 variants.","lang":"eng"}],"type":"journal_article","citation":{"ama":"Dormeshkin D, Shapira M, Dubovik S, et al. Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. <i>Frontiers in Immunology</i>. 2022;13. doi:<a href=\"https://doi.org/10.3389/fimmu.2022.965446\">10.3389/fimmu.2022.965446</a>","ieee":"D. Dormeshkin <i>et al.</i>, “Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library,” <i>Frontiers in Immunology</i>, vol. 13. Frontiers Media, 2022.","apa":"Dormeshkin, D., Shapira, M., Dubovik, S., Kavaleuski, A., Katsin, M., Migas, A., … Semyonov, S. (2022). Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. <i>Frontiers in Immunology</i>. Frontiers Media. <a href=\"https://doi.org/10.3389/fimmu.2022.965446\">https://doi.org/10.3389/fimmu.2022.965446</a>","mla":"Dormeshkin, Dmitri, et al. “Isolation of an Escape-Resistant SARS-CoV-2 Neutralizing Nanobody from a Novel Synthetic Nanobody Library.” <i>Frontiers in Immunology</i>, vol. 13, 965446, Frontiers Media, 2022, doi:<a href=\"https://doi.org/10.3389/fimmu.2022.965446\">10.3389/fimmu.2022.965446</a>.","ista":"Dormeshkin D, Shapira M, Dubovik S, Kavaleuski A, Katsin M, Migas A, Meleshko A, Semyonov S. 2022. Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. Frontiers in Immunology. 13, 965446.","chicago":"Dormeshkin, Dmitri, Michail Shapira, Simon Dubovik, Anton Kavaleuski, Mikalai Katsin, Alexandr Migas, Alexander Meleshko, and Sergei Semyonov. “Isolation of an Escape-Resistant SARS-CoV-2 Neutralizing Nanobody from a Novel Synthetic Nanobody Library.” <i>Frontiers in Immunology</i>. Frontiers Media, 2022. <a href=\"https://doi.org/10.3389/fimmu.2022.965446\">https://doi.org/10.3389/fimmu.2022.965446</a>.","short":"D. Dormeshkin, M. Shapira, S. Dubovik, A. Kavaleuski, M. Katsin, A. Migas, A. Meleshko, S. Semyonov, Frontiers in Immunology 13 (2022)."},"quality_controlled":"1","publisher":"Frontiers Media","volume":13,"department":[{"_id":"LeSa"}],"external_id":{"isi":["000862479100001"],"pmid":["36189235"]},"publication_status":"published","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"date_created":"2023-01-16T09:56:57Z","month":"09","scopus_import":"1","_id":"12252"},{"_id":"12261","scopus_import":"1","issue":"9","month":"09","date_created":"2023-01-16T09:58:34Z","publication_status":"published","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000856482800001"],"pmid":["36124745"]},"department":[{"_id":"ToBo"}],"volume":18,"publisher":"Embo Press","quality_controlled":"1","abstract":[{"text":"Dose–response relationships are a general concept for quantitatively describing biological systems across multiple scales, from the molecular to the whole-cell level. A clinically relevant example is the bacterial growth response to antibiotics, which is routinely characterized by dose–response curves. The shape of the dose–response curve varies drastically between antibiotics and plays a key role in treatment, drug interactions, and resistance evolution. However, the mechanisms shaping the dose–response curve remain largely unclear. Here, we show in Escherichia coli that the distinctively shallow dose–response curve of the antibiotic trimethoprim is caused by a negative growth-mediated feedback loop: Trimethoprim slows growth, which in turn weakens the effect of this antibiotic. At the molecular level, this feedback is caused by the upregulation of the drug target dihydrofolate reductase (FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim but follows a universal trend line that depends primarily on the growth rate, irrespective of its cause. Rewiring the feedback loop alters the dose–response curve in a predictable manner, which we corroborate using a mathematical model of cellular resource allocation and growth. Our results indicate that growth-mediated feedback loops may shape drug responses more generally and could be exploited to design evolutionary traps that enable selection against drug resistance.","lang":"eng"}],"type":"journal_article","pmid":1,"citation":{"ieee":"A. Angermayr, T. Y. Pang, G. Chevereau, K. Mitosch, M. J. Lercher, and M. T. Bollenbach, “Growth‐mediated negative feedback shapes quantitative antibiotic response,” <i>Molecular Systems Biology</i>, vol. 18, no. 9. Embo Press, 2022.","apa":"Angermayr, A., Pang, T. Y., Chevereau, G., Mitosch, K., Lercher, M. J., &#38; Bollenbach, M. T. (2022). Growth‐mediated negative feedback shapes quantitative antibiotic response. <i>Molecular Systems Biology</i>. Embo Press. <a href=\"https://doi.org/10.15252/msb.202110490\">https://doi.org/10.15252/msb.202110490</a>","ama":"Angermayr A, Pang TY, Chevereau G, Mitosch K, Lercher MJ, Bollenbach MT. Growth‐mediated negative feedback shapes quantitative antibiotic response. <i>Molecular Systems Biology</i>. 2022;18(9). doi:<a href=\"https://doi.org/10.15252/msb.202110490\">10.15252/msb.202110490</a>","mla":"Angermayr, Andreas, et al. “Growth‐mediated Negative Feedback Shapes Quantitative Antibiotic Response.” <i>Molecular Systems Biology</i>, vol. 18, no. 9, e10490, Embo Press, 2022, doi:<a href=\"https://doi.org/10.15252/msb.202110490\">10.15252/msb.202110490</a>.","ista":"Angermayr A, Pang TY, Chevereau G, Mitosch K, Lercher MJ, Bollenbach MT. 2022. Growth‐mediated negative feedback shapes quantitative antibiotic response. Molecular Systems Biology. 18(9), e10490.","chicago":"Angermayr, Andreas, Tin Yau Pang, Guillaume Chevereau, Karin Mitosch, Martin J Lercher, and Mark Tobias Bollenbach. “Growth‐mediated Negative Feedback Shapes Quantitative Antibiotic Response.” <i>Molecular Systems Biology</i>. Embo Press, 2022. <a href=\"https://doi.org/10.15252/msb.202110490\">https://doi.org/10.15252/msb.202110490</a>.","short":"A. Angermayr, T.Y. Pang, G. Chevereau, K. Mitosch, M.J. Lercher, M.T. Bollenbach, Molecular Systems Biology 18 (2022)."},"date_updated":"2025-06-11T14:10:18Z","author":[{"orcid":"0000-0001-8619-2223","full_name":"Angermayr, Andreas","last_name":"Angermayr","id":"4677C796-F248-11E8-B48F-1D18A9856A87","first_name":"Andreas"},{"full_name":"Pang, Tin Yau","last_name":"Pang","first_name":"Tin Yau"},{"first_name":"Guillaume","full_name":"Chevereau, Guillaume","last_name":"Chevereau"},{"first_name":"Karin","id":"39B66846-F248-11E8-B48F-1D18A9856A87","full_name":"Mitosch, Karin","last_name":"Mitosch"},{"first_name":"Martin J","full_name":"Lercher, Martin J","last_name":"Lercher"},{"first_name":"Mark Tobias","full_name":"Bollenbach, Mark Tobias","last_name":"Bollenbach","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4398-476X"}],"title":"Growth‐mediated negative feedback shapes quantitative antibiotic response","file_date_updated":"2023-01-30T09:49:55Z","has_accepted_license":"1","article_processing_charge":"No","status":"public","language":[{"iso":"eng"}],"oa_version":"Published Version","keyword":["Applied Mathematics","Computational Theory and Mathematics","General Agricultural and Biological Sciences","General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","Information Systems"],"publication":"Molecular Systems Biology","isi":1,"ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":"        18","date_published":"2022-09-01T00:00:00Z","doi":"10.15252/msb.202110490","day":"01","file":[{"file_id":"12446","date_updated":"2023-01-30T09:49:55Z","relation":"main_file","content_type":"application/pdf","checksum":"8b1d8f5ea20c8408acf466435fb6ae01","date_created":"2023-01-30T09:49:55Z","success":1,"file_name":"2022_MolecularSystemsBio_Angermayr.pdf","file_size":1098812,"creator":"dernst","access_level":"open_access"}],"oa":1,"acknowledgement":"This work was in part supported by Human Frontier Science Program GrantRGP0042/2013, Marie Curie Career Integration Grant303507, AustrianScience Fund (FWF) Grant P27201-B22, and German Research Foundation(DFG) Collaborative Research Center (SFB)1310to TB. SAA was supportedby the European Union’s Horizon2020Research and Innovation Programunder the Marie Skłodowska-Curie Grant agreement No707352. We wouldlike to thank the Bollenbach group for regular fruitful discussions. We areparticularly thankful for the technical assistance of Booshini Fernando andfor discussions of the theoretical aspects with Gerrit Ansmann. We areindebted to Bor Kavˇciˇc for invaluable advice, help with setting up theluciferase-based growth monitoring system, and for sharing plasmids. Weacknowledge the IST Austria Miba Machine Shop for their support inbuilding a housing for the stacker of the plate reader, which enabled thehigh-throughput luciferase-based experiments. We are grateful to RosalindAllen, Bor Kavˇciˇc and Dor Russ for feedback on the manuscript. Open Accessfunding enabled and organized by Projekt DEAL.","article_type":"original","publication_identifier":{"eissn":["1744-4292"]},"year":"2022","acknowledged_ssus":[{"_id":"M-Shop"}],"article_number":"e10490"},{"date_updated":"2025-04-15T08:29:05Z","author":[{"orcid":"0000-0002-4792-1881","id":"3320A096-F248-11E8-B48F-1D18A9856A87","last_name":"Sumser","full_name":"Sumser, Anton L","first_name":"Anton L"},{"first_name":"Maximilian A","orcid":"0000-0002-3937-1330","full_name":"Jösch, Maximilian A","last_name":"Jösch","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","full_name":"Jonas, Peter M"},{"last_name":"Ben Simon","full_name":"Ben Simon, Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav"}],"title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","file_date_updated":"2023-01-30T11:50:53Z","has_accepted_license":"1","article_processing_charge":"No","language":[{"iso":"eng"}],"status":"public","oa_version":"Published Version","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"publication":"eLife","isi":1,"ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","project":[{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"H2020","grant_number":"756502","name":"Circuits of Visual Attention","_id":"2634E9D2-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","name":"Synaptic communication in neuronal microcircuits","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"_id":"266D407A-B435-11E9-9278-68D0E5697425","name":"Neuronal networks of salience and spatial detection in the murine superior colliculus","grant_number":"LT000256"},{"name":"Connecting sensory with motor processing in the superior colliculus","_id":"264FEA02-B435-11E9-9278-68D0E5697425","grant_number":"ALTF 1098-2017"}],"intvolume":"        11","date_published":"2022-09-15T00:00:00Z","day":"15","doi":"10.7554/elife.79848","oa":1,"file":[{"date_updated":"2023-01-30T11:50:53Z","file_id":"12463","checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b","content_type":"application/pdf","relation":"main_file","creator":"dernst","file_size":8506811,"file_name":"2022_eLife_Sumser.pdf","date_created":"2023-01-30T11:50:53Z","success":1,"access_level":"open_access"}],"ec_funded":1,"year":"2022","article_type":"original","publication_identifier":{"eissn":["2050-084X"]},"acknowledgement":"We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript. This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical Facility (PCF). 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, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS).","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"article_number":"79848","_id":"12288","scopus_import":"1","month":"09","date_created":"2023-01-16T10:04:15Z","publication_status":"published","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000892204300001"],"pmid":["36040301"]},"department":[{"_id":"MaJö"},{"_id":"PeJo"}],"volume":11,"corr_author":"1","publisher":"eLife Sciences Publications","quality_controlled":"1","type":"journal_article","abstract":[{"text":"To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo.","lang":"eng"}],"pmid":1,"citation":{"ama":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>","ieee":"A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","apa":"Sumser, A. L., Jösch, M. A., Jonas, P. M., &#38; Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>","mla":"Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>, vol. 11, 79848, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.79848\">10.7554/elife.79848</a>.","chicago":"Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.79848\">https://doi.org/10.7554/elife.79848</a>.","ista":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 11, 79848.","short":"A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022)."}},{"external_id":{"isi":["000779305000033"],"pmid":["35019710"]},"publication_status":"published","date_created":"2022-01-18T10:04:18Z","month":"03","issue":"5","scopus_import":"1","_id":"10639","citation":{"ieee":"S. Windhaber <i>et al.</i>, “The Orthobunyavirus Germiston enters host cells from late endosomes,” <i>Journal of Virology</i>, vol. 96, no. 5. American Society for Microbiology, 2022.","apa":"Windhaber, S., Xin, Q., Uckeley, Z. M., Koch, J., Obr, M., Garnier, C., … Lozach, P.-Y. (2022). The Orthobunyavirus Germiston enters host cells from late endosomes. <i>Journal of Virology</i>. American Society for Microbiology. <a href=\"https://doi.org/10.1128/jvi.02146-21\">https://doi.org/10.1128/jvi.02146-21</a>","ama":"Windhaber S, Xin Q, Uckeley ZM, et al. The Orthobunyavirus Germiston enters host cells from late endosomes. <i>Journal of Virology</i>. 2022;96(5). doi:<a href=\"https://doi.org/10.1128/jvi.02146-21\">10.1128/jvi.02146-21</a>","chicago":"Windhaber, Stefan, Qilin Xin, Zina M. Uckeley, Jana Koch, Martin Obr, Céline Garnier, Catherine Luengo-Guyonnot, Maëva Duboeuf, Florian KM Schur, and Pierre-Yves Lozach. “The Orthobunyavirus Germiston Enters Host Cells from Late Endosomes.” <i>Journal of Virology</i>. American Society for Microbiology, 2022. <a href=\"https://doi.org/10.1128/jvi.02146-21\">https://doi.org/10.1128/jvi.02146-21</a>.","ista":"Windhaber S, Xin Q, Uckeley ZM, Koch J, Obr M, Garnier C, Luengo-Guyonnot C, Duboeuf M, Schur FK, Lozach P-Y. 2022. The Orthobunyavirus Germiston enters host cells from late endosomes. Journal of Virology. 96(5), e02146-21.","mla":"Windhaber, Stefan, et al. “The Orthobunyavirus Germiston Enters Host Cells from Late Endosomes.” <i>Journal of Virology</i>, vol. 96, no. 5, e02146-21, American Society for Microbiology, 2022, doi:<a href=\"https://doi.org/10.1128/jvi.02146-21\">10.1128/jvi.02146-21</a>.","short":"S. Windhaber, Q. Xin, Z.M. Uckeley, J. Koch, M. Obr, C. Garnier, C. Luengo-Guyonnot, M. Duboeuf, F.K. Schur, P.-Y. Lozach, Journal of Virology 96 (2022)."},"pmid":1,"abstract":[{"text":"With more than 80 members worldwide, the Orthobunyavirus genus in the Peribunyaviridae family is a large genus of enveloped RNA viruses, many of which are emerging pathogens in humans and livestock. How orthobunyaviruses (OBVs) penetrate and infect mammalian host cells remains poorly characterized. Here, we investigated the entry mechanisms of the OBV Germiston (GERV). Viral particles were visualized by cryo-electron microscopy and appeared roughly spherical with an average diameter of 98 nm. Labeling of the virus with fluorescent dyes did not adversely affect its infectivity and allowed the monitoring of single particles in fixed and live cells. Using this approach, we found that endocytic internalization of bound viruses was asynchronous and occurred within 30-40 min. The virus entered Rab5a+ early endosomes and, subsequently, late endosomal vacuoles containing Rab7a but not LAMP-1. Infectious entry did not require proteolytic cleavage, and endosomal acidification was sufficient and necessary for viral fusion. Acid-activated penetration began 15-25 min after initiation of virus internalization and relied on maturation of early endosomes to late endosomes. The optimal pH for viral membrane fusion was slightly below 6.0, and penetration was hampered when the potassium influx was abolished. Overall, our study provides real-time visualization of GERV entry into host cells and demonstrates the importance of late endosomal maturation in facilitating OBV penetration.","lang":"eng"}],"type":"journal_article","quality_controlled":"1","publisher":"American Society for Microbiology","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906410","open_access":"1"}],"volume":96,"department":[{"_id":"FlSc"}],"keyword":["virology","insect science","immunology","microbiology"],"oa_version":"Published Version","status":"public","language":[{"iso":"eng"}],"article_processing_charge":"No","title":"The Orthobunyavirus Germiston enters host cells from late endosomes","author":[{"first_name":"Stefan","full_name":"Windhaber, Stefan","last_name":"Windhaber"},{"full_name":"Xin, Qilin","last_name":"Xin","first_name":"Qilin"},{"first_name":"Zina M.","last_name":"Uckeley","full_name":"Uckeley, Zina M."},{"first_name":"Jana","full_name":"Koch, Jana","last_name":"Koch"},{"first_name":"Martin","orcid":"0000-0003-1756-6564","full_name":"Obr, Martin","last_name":"Obr","id":"4741CA5A-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Garnier, Céline","last_name":"Garnier","first_name":"Céline"},{"first_name":"Catherine","full_name":"Luengo-Guyonnot, Catherine","last_name":"Luengo-Guyonnot"},{"first_name":"Maëva","last_name":"Duboeuf","full_name":"Duboeuf, Maëva"},{"first_name":"Florian KM","orcid":"0000-0003-4790-8078","last_name":"Schur","full_name":"Schur, Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Lozach, Pierre-Yves","last_name":"Lozach","first_name":"Pierre-Yves"}],"date_updated":"2025-04-15T08:24:49Z","article_number":"e02146-21","acknowledged_ssus":[{"_id":"EM-Fac"}],"article_type":"original","year":"2022","publication_identifier":{"eissn":["1098-5514"],"issn":["0022-538X"]},"acknowledgement":"This work  was  supported  by  INRAE  starter  funds, Project IDEXLYON  (University  of  Lyon) within  the  Programme  Investissements  d’Avenir  (ANR-16-IDEX-0005),  and  FINOVIAO14 (Fondation  pour  l’Université  de  Lyon),  all  to  P.Y.L.  This  work  was  also  supported  by CellNetworks  Research  Group  funds  and  Deutsche  Forschungsgemeinschaft  (DFG)  funding (grant  numbers  LO-2338/1-1  and  LO-2338/3-1)  awarded  to  P.Y.L., Austrian  Science  Fund (FWF)  grant  P31445  to  F.K.M.S., a  Chinese  Scholarship  Council (CSC;no.  201904910701) fellowship  to   Q.X.,  and  a  ministére  de  l’enseignement  supérieur,  de  la  recherche  et  de l’innovation (MESRI) doctoral thesis grant to M.D.","oa":1,"doi":"10.1128/jvi.02146-21","day":"01","date_published":"2022-03-01T00:00:00Z","intvolume":"        96","project":[{"grant_number":"P31445","_id":"26736D6A-B435-11E9-9278-68D0E5697425","name":"Structural conservation and diversity in retroviral capsid","call_identifier":"FWF"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","isi":1,"publication":"Journal of Virology"},{"publisher":"Springer Nature","department":[{"_id":"CaGu"}],"volume":20,"quality_controlled":"1","citation":{"ieee":"R. Römhild, M. T. Bollenbach, and D. I. Andersson, “The physiology and genetics of bacterial responses to antibiotic combinations,” <i>Nature Reviews Microbiology</i>, vol. 20. Springer Nature, pp. 478–490, 2022.","ama":"Römhild R, Bollenbach MT, Andersson DI. The physiology and genetics of bacterial responses to antibiotic combinations. <i>Nature Reviews Microbiology</i>. 2022;20:478-490. doi:<a href=\"https://doi.org/10.1038/s41579-022-00700-5\">10.1038/s41579-022-00700-5</a>","apa":"Römhild, R., Bollenbach, M. T., &#38; Andersson, D. I. (2022). The physiology and genetics of bacterial responses to antibiotic combinations. <i>Nature Reviews Microbiology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41579-022-00700-5\">https://doi.org/10.1038/s41579-022-00700-5</a>","ista":"Römhild R, Bollenbach MT, Andersson DI. 2022. The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. 20, 478–490.","chicago":"Römhild, Roderich, Mark Tobias Bollenbach, and Dan I. Andersson. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” <i>Nature Reviews Microbiology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41579-022-00700-5\">https://doi.org/10.1038/s41579-022-00700-5</a>.","mla":"Römhild, Roderich, et al. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” <i>Nature Reviews Microbiology</i>, vol. 20, Springer Nature, 2022, pp. 478–90, doi:<a href=\"https://doi.org/10.1038/s41579-022-00700-5\">10.1038/s41579-022-00700-5</a>.","short":"R. Römhild, M.T. Bollenbach, D.I. Andersson, Nature Reviews Microbiology 20 (2022) 478–490."},"type":"journal_article","pmid":1,"abstract":[{"lang":"eng","text":"Several promising strategies based on combining or cycling different antibiotics have been proposed to increase efficacy and counteract resistance evolution, but we still lack a deep understanding of the physiological responses and genetic mechanisms that underlie antibiotic interactions and the clinical applicability of these strategies. In antibiotic-exposed bacteria, the combined effects of physiological stress responses and emerging resistance mutations (occurring at different time scales) generate complex and often unpredictable dynamics. In this Review, we present our current understanding of bacterial cell physiology and genetics of responses to antibiotics. We emphasize recently discovered mechanisms of synergistic and antagonistic drug interactions, hysteresis in temporal interactions between antibiotics that arise from microbial physiology and interactions between antibiotics and resistance mutations that can cause collateral sensitivity or cross-resistance. We discuss possible connections between the different phenomena and indicate relevant research directions. A better and more unified understanding of drug and genetic interactions is likely to advance antibiotic therapy."}],"scopus_import":"1","month":"08","_id":"10812","external_id":{"isi":["000763891900001"],"pmid":["35241807"]},"date_created":"2022-03-04T04:33:49Z","publication_status":"published","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","isi":1,"publication":"Nature Reviews Microbiology","publication_identifier":{"eissn":["1740-1534"],"issn":["1740-1526"]},"year":"2022","acknowledgement":"The authors thank B. Kavčič and H. Schulenburg for constructive feedback on the manuscript.","article_type":"review","date_published":"2022-08-01T00:00:00Z","intvolume":"        20","doi":"10.1038/s41579-022-00700-5","day":"01","article_processing_charge":"No","status":"public","language":[{"iso":"eng"}],"page":"478-490","date_updated":"2023-08-02T14:41:44Z","title":"The physiology and genetics of bacterial responses to antibiotic combinations","author":[{"first_name":"Roderich","orcid":"0000-0001-9480-5261","id":"68E56E44-62B0-11EA-B963-444F3DDC885E","full_name":"Römhild, Roderich","last_name":"Römhild"},{"orcid":"0000-0003-4398-476X","full_name":"Bollenbach, Mark Tobias","last_name":"Bollenbach","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","first_name":"Mark Tobias"},{"last_name":"Andersson","full_name":"Andersson, Dan I.","first_name":"Dan I."}],"keyword":["General Immunology and Microbiology","Microbiology","Infectious Diseases"],"oa_version":"None"},{"volume":11,"department":[{"_id":"GradSch"},{"_id":"FyKo"}],"corr_author":"1","publisher":"eLife Sciences Publications","citation":{"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).","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>.","chicago":"Gonzalez Somermeyer, Louisa, Aubin Fleiss, Alexander S Mishin, Nina G Bozhanova, Anna A Igolkina, Jens Meiler, Maria-Elisenda Alaball Pujol, Ekaterina V Putintseva, Karen S Sarkisyan, and Fyodor Kondrashov. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.75842\">https://doi.org/10.7554/elife.75842</a>.","ista":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, Bozhanova NG, Igolkina AA, Meiler J, Alaball Pujol M-E, Putintseva EV, Sarkisyan KS, Kondrashov F. 2022. Heterogeneity of the GFP fitness landscape and data-driven protein design. eLife. 11, 75842.","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>","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>","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."},"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"}],"type":"journal_article","pmid":1,"quality_controlled":"1","_id":"11448","month":"05","scopus_import":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"publication_status":"published","date_created":"2022-06-18T09:06:59Z","external_id":{"pmid":["35510622"],"isi":["000799197200001"]},"isi":1,"publication":"eLife","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","project":[{"call_identifier":"H2020","grant_number":"771209","name":"Characterizing the fitness landscape on population and global scales","_id":"26580278-B435-11E9-9278-68D0E5697425"},{"grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"ddc":["570"],"oa":1,"file":[{"file_id":"11454","date_updated":"2022-06-20T07:44:19Z","relation":"main_file","content_type":"application/pdf","checksum":"7573c28f44028ab0cc81faef30039e44","file_size":5297213,"creator":"dernst","file_name":"2022_eLife_Somermeyer.pdf","success":1,"date_created":"2022-06-20T07:44:19Z","access_level":"open_access"}],"day":"05","doi":"10.7554/elife.75842","date_published":"2022-05-05T00:00:00Z","intvolume":"        11","article_number":"75842","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"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.","publication_identifier":{"issn":["2050-084X"]},"year":"2022","article_type":"original","ec_funded":1,"author":[{"first_name":"Louisa","orcid":"0000-0001-9139-5383","last_name":"Gonzalez Somermeyer","full_name":"Gonzalez Somermeyer, Louisa","id":"4720D23C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Aubin","last_name":"Fleiss","full_name":"Fleiss, Aubin"},{"last_name":"Mishin","full_name":"Mishin, Alexander S","first_name":"Alexander S"},{"first_name":"Nina G","full_name":"Bozhanova, Nina G","last_name":"Bozhanova"},{"first_name":"Anna A","full_name":"Igolkina, Anna A","last_name":"Igolkina"},{"full_name":"Meiler, Jens","last_name":"Meiler","first_name":"Jens"},{"last_name":"Alaball Pujol","full_name":"Alaball Pujol, Maria-Elisenda","first_name":"Maria-Elisenda"},{"full_name":"Putintseva, Ekaterina V","last_name":"Putintseva","first_name":"Ekaterina V"},{"last_name":"Sarkisyan","full_name":"Sarkisyan, Karen S","first_name":"Karen S"},{"id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","full_name":"Kondrashov, Fyodor","last_name":"Kondrashov","orcid":"0000-0001-8243-4694","first_name":"Fyodor"}],"title":"Heterogeneity of the GFP fitness landscape and data-driven protein design","date_updated":"2026-04-07T13:25:01Z","related_material":{"link":[{"relation":"software","url":"https://github.com/aequorea238/Orthologous_GFP_Fitness_Peaks"}],"record":[{"id":"17850","relation":"dissertation_contains","status":"public"}]},"language":[{"iso":"eng"}],"status":"public","article_processing_charge":"No","has_accepted_license":"1","file_date_updated":"2022-06-20T07:44:19Z","oa_version":"Published Version","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"]},{"external_id":{"isi":["000812509800001"],"pmid":["35713756"]},"publication_status":"published","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"date_created":"2022-06-17T16:16:15Z","month":"06","scopus_import":"1","issue":"8","_id":"11447","abstract":[{"lang":"eng","text":"Empirical essays of fitness landscapes suggest that they may be rugged, that is having multiple fitness peaks. Such fitness landscapes, those that have multiple peaks, necessarily have special local structures, called reciprocal sign epistasis (Poelwijk et al. in J Theor Biol 272:141–144, 2011). Here, we investigate the quantitative relationship between the number of fitness peaks and the number of reciprocal sign epistatic interactions. Previously, it has been shown (Poelwijk et al. in J Theor Biol 272:141–144, 2011) that pairwise reciprocal sign epistasis is a necessary but not sufficient condition for the existence of multiple peaks. Applying discrete Morse theory, which to our knowledge has never been used in this context, we extend this result by giving the minimal number of reciprocal sign epistatic interactions required to create a given number of peaks."}],"pmid":1,"type":"journal_article","citation":{"ista":"Saona Urmeneta RJ, Kondrashov F, Khudiakova K. 2022. Relation between the number of peaks and the number of reciprocal sign epistatic interactions. Bulletin of Mathematical Biology. 84(8), 74.","chicago":"Saona Urmeneta, Raimundo J, Fyodor Kondrashov, and Kseniia Khudiakova. “Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic Interactions.” <i>Bulletin of Mathematical Biology</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1007/s11538-022-01029-z\">https://doi.org/10.1007/s11538-022-01029-z</a>.","mla":"Saona Urmeneta, Raimundo J., et al. “Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic Interactions.” <i>Bulletin of Mathematical Biology</i>, vol. 84, no. 8, 74, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1007/s11538-022-01029-z\">10.1007/s11538-022-01029-z</a>.","ama":"Saona Urmeneta RJ, Kondrashov F, Khudiakova K. Relation between the number of peaks and the number of reciprocal sign epistatic interactions. <i>Bulletin of Mathematical Biology</i>. 2022;84(8). doi:<a href=\"https://doi.org/10.1007/s11538-022-01029-z\">10.1007/s11538-022-01029-z</a>","ieee":"R. J. Saona Urmeneta, F. Kondrashov, and K. Khudiakova, “Relation between the number of peaks and the number of reciprocal sign epistatic interactions,” <i>Bulletin of Mathematical Biology</i>, vol. 84, no. 8. Springer Nature, 2022.","apa":"Saona Urmeneta, R. J., Kondrashov, F., &#38; Khudiakova, K. (2022). Relation between the number of peaks and the number of reciprocal sign epistatic interactions. <i>Bulletin of Mathematical Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1007/s11538-022-01029-z\">https://doi.org/10.1007/s11538-022-01029-z</a>","short":"R.J. Saona Urmeneta, F. Kondrashov, K. Khudiakova, Bulletin of Mathematical Biology 84 (2022)."},"quality_controlled":"1","publisher":"Springer Nature","corr_author":"1","volume":84,"department":[{"_id":"GradSch"},{"_id":"NiBa"},{"_id":"JaMa"}],"keyword":["Computational Theory and Mathematics","General Agricultural and Biological Sciences","Pharmacology","General Environmental Science","General Biochemistry","Genetics and Molecular Biology","General Mathematics","Immunology","General Neuroscience"],"oa_version":"Published Version","language":[{"iso":"eng"}],"status":"public","file_date_updated":"2022-06-20T07:51:32Z","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","title":"Relation between the number of peaks and the number of reciprocal sign epistatic interactions","author":[{"full_name":"Saona Urmeneta, Raimundo J","last_name":"Saona Urmeneta","id":"BD1DF4C4-D767-11E9-B658-BC13E6697425","orcid":"0000-0001-5103-038X","first_name":"Raimundo J"},{"first_name":"Fyodor","full_name":"Kondrashov, Fyodor","last_name":"Kondrashov","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8243-4694"},{"first_name":"Kseniia","id":"4E6DC800-AE37-11E9-AC72-31CAE5697425","full_name":"Khudiakova, Kseniia","last_name":"Khudiakova","orcid":"0000-0002-6246-1465"}],"date_updated":"2026-04-15T08:51:10Z","related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1007/s11538-022-01118-z"}]},"article_number":"74","ec_funded":1,"publication_identifier":{"issn":["0092-8240"],"eissn":["1522-9602"]},"article_type":"original","year":"2022","acknowledgement":"We are grateful to Herbert Edelsbrunner and Jeferson Zapata for helpful discussions. Open access funding provided by Austrian Science Fund (FWF). Partially supported by the ERC Consolidator (771209–CharFL) and the FWF Austrian Science Fund (I5127-B) grants to FAK.","doi":"10.1007/s11538-022-01029-z","day":"17","oa":1,"file":[{"access_level":"open_access","file_size":463025,"creator":"dernst","file_name":"2022_BulletinMathBiology_Saona.pdf","success":1,"date_created":"2022-06-20T07:51:32Z","relation":"main_file","content_type":"application/pdf","checksum":"05a1fe7d10914a00c2bca9b447993a65","file_id":"11455","date_updated":"2022-06-20T07:51:32Z"}],"intvolume":"        84","date_published":"2022-06-17T00:00:00Z","project":[{"grant_number":"771209","name":"Characterizing the fitness landscape on population and global scales","_id":"26580278-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"I05127","name":"Evolutionary analysis of gene regulation","_id":"34e076d6-11ca-11ed-8bc3-aec76c41a181"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["510","570"],"publication":"Bulletin of Mathematical Biology","isi":1},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication":"The EMBO Journal","article_number":"e107711","publication_identifier":{"issn":["0261-4189"],"eissn":["1460-2075"]},"year":"2021","article_type":"original","oa":1,"day":"02","doi":"10.15252/embj.2021107711","date_published":"2021-11-02T00:00:00Z","intvolume":"        40","language":[{"iso":"eng"}],"status":"public","article_processing_charge":"Yes","author":[{"first_name":"Florian","full_name":"Geiger, Florian","last_name":"Geiger"},{"first_name":"Julia","full_name":"Acker, Julia","last_name":"Acker"},{"full_name":"Papa, Guido","last_name":"Papa","first_name":"Guido"},{"first_name":"Xinyu","full_name":"Wang, Xinyu","last_name":"Wang"},{"first_name":"William E","last_name":"Arter","full_name":"Arter, William E"},{"full_name":"Saar, Kadi L","last_name":"Saar","first_name":"Kadi L"},{"first_name":"Nadia A","full_name":"Erkamp, Nadia A","last_name":"Erkamp"},{"first_name":"Runzhang","full_name":"Qi, Runzhang","last_name":"Qi"},{"orcid":"0000-0003-0456-0753","full_name":"Bravo, Jack Peter Kelly","last_name":"Bravo","id":"96aecfa5-8931-11ee-af30-aa6a5d6eee0e","first_name":"Jack Peter Kelly"},{"first_name":"Sebastian","last_name":"Strauss","full_name":"Strauss, Sebastian"},{"first_name":"Georg","full_name":"Krainer, Georg","last_name":"Krainer"},{"full_name":"Burrone, Oscar R","last_name":"Burrone","first_name":"Oscar R"},{"full_name":"Jungmann, Ralf","last_name":"Jungmann","first_name":"Ralf"},{"first_name":"Tuomas PJ","full_name":"Knowles, Tuomas PJ","last_name":"Knowles"},{"first_name":"Hanna","full_name":"Engelke, Hanna","last_name":"Engelke"},{"first_name":"Alexander","full_name":"Borodavka, Alexander","last_name":"Borodavka"}],"title":"Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses","date_updated":"2024-06-04T06:08:16Z","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","Molecular Biology","General Neuroscience"],"oa_version":"Published Version","publisher":"Embo Press","main_file_link":[{"open_access":"1","url":"https://doi.org/10.15252/embj.2021107711"}],"volume":40,"citation":{"short":"F. Geiger, J. Acker, G. Papa, X. Wang, W.E. Arter, K.L. Saar, N.A. Erkamp, R. Qi, J.P.K. Bravo, S. Strauss, G. Krainer, O.R. Burrone, R. Jungmann, T.P. Knowles, H. Engelke, A. Borodavka, The EMBO Journal 40 (2021).","mla":"Geiger, Florian, et al. “Liquid–Liquid Phase Separation Underpins the Formation of Replication Factories in Rotaviruses.” <i>The EMBO Journal</i>, vol. 40, no. 21, e107711, Embo Press, 2021, doi:<a href=\"https://doi.org/10.15252/embj.2021107711\">10.15252/embj.2021107711</a>.","ista":"Geiger F, Acker J, Papa G, Wang X, Arter WE, Saar KL, Erkamp NA, Qi R, Bravo JPK, Strauss S, Krainer G, Burrone OR, Jungmann R, Knowles TP, Engelke H, Borodavka A. 2021. Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses. The EMBO Journal. 40(21), e107711.","chicago":"Geiger, Florian, Julia Acker, Guido Papa, Xinyu Wang, William E Arter, Kadi L Saar, Nadia A Erkamp, et al. “Liquid–Liquid Phase Separation Underpins the Formation of Replication Factories in Rotaviruses.” <i>The EMBO Journal</i>. Embo Press, 2021. <a href=\"https://doi.org/10.15252/embj.2021107711\">https://doi.org/10.15252/embj.2021107711</a>.","ama":"Geiger F, Acker J, Papa G, et al. Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses. <i>The EMBO Journal</i>. 2021;40(21). doi:<a href=\"https://doi.org/10.15252/embj.2021107711\">10.15252/embj.2021107711</a>","apa":"Geiger, F., Acker, J., Papa, G., Wang, X., Arter, W. E., Saar, K. L., … Borodavka, A. (2021). Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses. <i>The EMBO Journal</i>. Embo Press. <a href=\"https://doi.org/10.15252/embj.2021107711\">https://doi.org/10.15252/embj.2021107711</a>","ieee":"F. Geiger <i>et al.</i>, “Liquid–liquid phase separation underpins the formation of replication factories in rotaviruses,” <i>The EMBO Journal</i>, vol. 40, no. 21. Embo Press, 2021."},"pmid":1,"extern":"1","type":"journal_article","abstract":[{"lang":"eng","text":"RNA viruses induce the formation of subcellular organelles that provide microenvironments conducive to their replication. Here we show that replication factories of rotaviruses represent protein‐RNA condensates that are formed via liquid–liquid phase separation of the viroplasm‐forming proteins NSP5 and rotavirus RNA chaperone NSP2. Upon mixing, these proteins readily form condensates at physiologically relevant low micromolar concentrations achieved in the cytoplasm of virus‐infected cells. Early infection stage condensates could be reversibly dissolved by 1,6‐hexanediol, as well as propylene glycol that released rotavirus transcripts from these condensates. During the early stages of infection, propylene glycol treatments reduced viral replication and phosphorylation of the condensate‐forming protein NSP5. During late infection, these condensates exhibited altered material properties and became resistant to propylene glycol, coinciding with hyperphosphorylation of NSP5. Some aspects of the assembly of cytoplasmic rotavirus replication factories mirror the formation of other ribonucleoprotein granules. Such viral RNA‐rich condensates that support replication of multi‐segmented genomes represent an attractive target for developing novel therapeutic approaches."}],"quality_controlled":"1","month":"11","issue":"21","scopus_import":"1","_id":"15138","external_id":{"pmid":["34524703"]},"publication_status":"published","date_created":"2024-03-20T10:42:39Z"},{"department":[{"_id":"PeJo"}],"volume":10,"publisher":"eLife Sciences Publications","quality_controlled":"1","pmid":1,"type":"journal_article","abstract":[{"lang":"eng","text":"Synapses of glutamatergic mossy fibers (MFs) onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC’s large dendritic brush. Using mouse brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBCs. The source of this ambient glutamate was spontaneous, spike-independent exocytosis from the MF terminal, and its level was dependent on activity of glutamate transporters EAAT1–2. Increasing levels of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs and altered the phase of responses to in vivo-like synaptic activity. Unlike classical fast synapses, receptors at the UBC synapse are virtually always exposed to a significant level of glutamate, which varies in a graded manner during transmission."}],"citation":{"short":"T.S. Balmer, C. Borges Merjane, L.O. Trussell, ELife 10 (2021).","mla":"Balmer, Timothy S., et al. “Incomplete Removal of Extracellular Glutamate Controls Synaptic Transmission and Integration at a Cerebellar Synapse.” <i>ELife</i>, vol. 10, e63819, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/elife.63819\">10.7554/elife.63819</a>.","ista":"Balmer TS, Borges Merjane C, Trussell LO. 2021. Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse. eLife. 10, e63819.","chicago":"Balmer, Timothy S, Carolina Borges Merjane, and Laurence O Trussell. “Incomplete Removal of Extracellular Glutamate Controls Synaptic Transmission and Integration at a Cerebellar Synapse.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/elife.63819\">https://doi.org/10.7554/elife.63819</a>.","ieee":"T. S. Balmer, C. Borges Merjane, and L. O. Trussell, “Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","apa":"Balmer, T. S., Borges Merjane, C., &#38; Trussell, L. O. (2021). Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.63819\">https://doi.org/10.7554/elife.63819</a>","ama":"Balmer TS, Borges Merjane C, Trussell LO. Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/elife.63819\">10.7554/elife.63819</a>"},"_id":"15273","month":"02","date_created":"2024-04-03T07:58:11Z","publication_status":"published","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["33616036"]},"publication":"eLife","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":"        10","date_published":"2021-02-22T00:00:00Z","doi":"10.7554/elife.63819","day":"22","oa":1,"file":[{"access_level":"open_access","file_name":"2021_eLife_Balmer.pdf","date_created":"2024-04-09T11:13:07Z","success":1,"file_size":6997954,"creator":"dernst","relation":"main_file","content_type":"application/pdf","checksum":"bbd4de2e54b7fbc11fba14f59e87fe3f","file_id":"15307","date_updated":"2024-04-09T11:13:07Z"}],"year":"2021","article_type":"original","publication_identifier":{"issn":["2050-084X"]},"article_number":"e63819","date_updated":"2024-04-09T11:15:01Z","title":"Incomplete removal of extracellular glutamate controls synaptic transmission and integration at a cerebellar synapse","author":[{"first_name":"Timothy S","full_name":"Balmer, Timothy S","last_name":"Balmer"},{"first_name":"Carolina","orcid":"0000-0003-0005-401X","full_name":"Borges Merjane, Carolina","last_name":"Borges Merjane","id":"4305C450-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Laurence O","full_name":"Trussell, Laurence O","last_name":"Trussell"}],"file_date_updated":"2024-04-09T11:13:07Z","article_processing_charge":"Yes","has_accepted_license":"1","language":[{"iso":"eng"}],"status":"public","oa_version":"Published Version","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"]},{"citation":{"short":"F. Navarrete, N. Grujic, A. Stirnberg, I. Saado, D. Aleksza, M.C. Gallei, H. Adi, A. Alcântara, M. Khan, J. Bindics, M. Trujillo, A. Djamei, PLOS Pathogens 17 (2021).","mla":"Navarrete, Fernando, et al. “The Pleiades Are a Cluster of Fungal Effectors That Inhibit Host Defenses.” <i>PLOS Pathogens</i>, vol. 17, no. 6, e1009641, Public Library of Science, 2021, doi:<a href=\"https://doi.org/10.1371/journal.ppat.1009641\">10.1371/journal.ppat.1009641</a>.","ista":"Navarrete F, Grujic N, Stirnberg A, Saado I, Aleksza D, Gallei MC, Adi H, Alcântara A, Khan M, Bindics J, Trujillo M, Djamei A. 2021. The Pleiades are a cluster of fungal effectors that inhibit host defenses. PLOS Pathogens. 17(6), e1009641.","chicago":"Navarrete, Fernando, Nenad Grujic, Alexandra Stirnberg, Indira Saado, David Aleksza, Michelle C Gallei, Hazem Adi, et al. “The Pleiades Are a Cluster of Fungal Effectors That Inhibit Host Defenses.” <i>PLOS Pathogens</i>. Public Library of Science, 2021. <a href=\"https://doi.org/10.1371/journal.ppat.1009641\">https://doi.org/10.1371/journal.ppat.1009641</a>.","apa":"Navarrete, F., Grujic, N., Stirnberg, A., Saado, I., Aleksza, D., Gallei, M. C., … Djamei, A. (2021). The Pleiades are a cluster of fungal effectors that inhibit host defenses. <i>PLOS Pathogens</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.ppat.1009641\">https://doi.org/10.1371/journal.ppat.1009641</a>","ama":"Navarrete F, Grujic N, Stirnberg A, et al. The Pleiades are a cluster of fungal effectors that inhibit host defenses. <i>PLOS Pathogens</i>. 2021;17(6). doi:<a href=\"https://doi.org/10.1371/journal.ppat.1009641\">10.1371/journal.ppat.1009641</a>","ieee":"F. Navarrete <i>et al.</i>, “The Pleiades are a cluster of fungal effectors that inhibit host defenses,” <i>PLOS Pathogens</i>, vol. 17, no. 6. Public Library of Science, 2021."},"type":"journal_article","pmid":1,"abstract":[{"text":"Biotrophic plant pathogens secrete effector proteins to manipulate the host physiology. Effectors suppress defenses and induce an environment favorable to disease development. Sequence-based prediction of effector function is impeded by their rapid evolution rate. In the maize pathogen <jats:italic>Ustilago maydis</jats:italic>, effector-coding genes frequently organize in clusters. Here we describe the functional characterization of the <jats:italic>pleiades</jats:italic>, a cluster of ten effector genes, by analyzing the micro- and macroscopic phenotype of the cluster deletion and expressing these proteins <jats:italic>in planta</jats:italic>. Deletion of the <jats:italic>pleiades</jats:italic> leads to strongly impaired virulence and accumulation of reactive oxygen species (ROS) in infected tissue. Eight of the Pleiades suppress the production of ROS upon perception of pathogen associated molecular patterns (PAMPs). Although functionally redundant, the Pleiades target different host components. The paralogs Taygeta1 and Merope1 suppress ROS production in either the cytoplasm or nucleus, respectively. Merope1 targets and promotes the auto-ubiquitination activity of RFI2, a conserved family of E3 ligases that regulates the production of PAMP-triggered ROS burst in plants.","lang":"eng"}],"quality_controlled":"1","volume":17,"department":[{"_id":"JiFr"}],"publisher":"Public Library of Science","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"publication_status":"published","date_created":"2024-04-03T08:00:34Z","external_id":{"pmid":["34166468"]},"_id":"15276","month":"06","issue":"6","file":[{"file_id":"15305","date_updated":"2024-04-09T10:24:43Z","relation":"main_file","content_type":"application/pdf","checksum":"ab8428291a0c14607c4ea5656c029cff","success":1,"file_name":"2021_PlosPathogens_Navarrete.pdf","date_created":"2024-04-09T10:24:43Z","file_size":2616563,"creator":"dernst","access_level":"open_access"}],"oa":1,"doi":"10.1371/journal.ppat.1009641","day":"24","date_published":"2021-06-24T00:00:00Z","intvolume":"        17","article_number":"e1009641","year":"2021","article_type":"original","publication_identifier":{"issn":["1553-7374"]},"publication":"PLOS Pathogens","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["580"],"oa_version":"Published Version","keyword":["Virology","Genetics","Molecular Biology","Immunology","Microbiology","Parasitology"],"author":[{"full_name":"Navarrete, Fernando","last_name":"Navarrete","first_name":"Fernando"},{"first_name":"Nenad","last_name":"Grujic","full_name":"Grujic, Nenad"},{"first_name":"Alexandra","full_name":"Stirnberg, Alexandra","last_name":"Stirnberg"},{"first_name":"Indira","full_name":"Saado, Indira","last_name":"Saado"},{"first_name":"David","last_name":"Aleksza","full_name":"Aleksza, David"},{"orcid":"0000-0003-1286-7368","full_name":"Gallei, Michelle C","last_name":"Gallei","id":"35A03822-F248-11E8-B48F-1D18A9856A87","first_name":"Michelle C"},{"last_name":"Adi","full_name":"Adi, Hazem","first_name":"Hazem"},{"last_name":"Alcântara","full_name":"Alcântara, André","first_name":"André"},{"full_name":"Khan, Mamoona","last_name":"Khan","first_name":"Mamoona"},{"first_name":"Janos","full_name":"Bindics, Janos","last_name":"Bindics"},{"full_name":"Trujillo, Marco","last_name":"Trujillo","first_name":"Marco"},{"first_name":"Armin","last_name":"Djamei","full_name":"Djamei, Armin"}],"title":"The Pleiades are a cluster of fungal effectors that inhibit host defenses","date_updated":"2024-04-09T10:26:12Z","language":[{"iso":"eng"}],"status":"public","has_accepted_license":"1","article_processing_charge":"Yes","file_date_updated":"2024-04-09T10:24:43Z"},{"author":[{"last_name":"Pranger","full_name":"Pranger, Christina L.","first_name":"Christina L."},{"orcid":"0000-0002-8777-3502","id":"36432834-F248-11E8-B48F-1D18A9856A87","last_name":"Fazekas-Singer","full_name":"Fazekas-Singer, Judit","first_name":"Judit"},{"full_name":"Köhler, Verena K.","last_name":"Köhler","first_name":"Verena K."},{"last_name":"Pali‐Schöll","full_name":"Pali‐Schöll, Isabella","first_name":"Isabella"},{"first_name":"Alessandro","full_name":"Fiocchi, Alessandro","last_name":"Fiocchi"},{"first_name":"Sophia N.","last_name":"Karagiannis","full_name":"Karagiannis, Sophia N."},{"first_name":"Olatz","full_name":"Zenarruzabeitia, Olatz","last_name":"Zenarruzabeitia"},{"full_name":"Borrego, Francisco","last_name":"Borrego","first_name":"Francisco"},{"first_name":"Erika","last_name":"Jensen‐Jarolim","full_name":"Jensen‐Jarolim, Erika"}],"title":"PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow's milk allergy and tolerance","page":"1553-1556","date_updated":"2023-09-05T15:58:53Z","status":"public","language":[{"iso":"eng"}],"file_date_updated":"2022-03-08T11:23:16Z","article_processing_charge":"No","has_accepted_license":"1","oa_version":"Published Version","keyword":["Immunology","Immunology and Allergy"],"publication":"Allergy","isi":1,"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","ddc":["570"],"doi":"10.1111/all.14604","day":"01","file":[{"date_created":"2022-03-08T11:23:16Z","success":1,"file_name":"2021_Allergy_Pranger.pdf","creator":"dernst","file_size":626081,"access_level":"open_access","date_updated":"2022-03-08T11:23:16Z","file_id":"10837","checksum":"9526f9554112fc027c9f7fa540c488cd","content_type":"application/pdf","relation":"main_file"}],"oa":1,"intvolume":"        76","date_published":"2021-05-01T00:00:00Z","publication_identifier":{"eissn":["1398-9995"],"issn":["0105-4538"]},"year":"2021","article_type":"letter_note","acknowledgement":"This  work  was  supported  by  the  Austrian  Science  Fund  (FWF)  grants  MCCA  W1248-B30  and  SFB  F4606-B28  to  EJJ.  CP  received  a  short-term research fellowship of the European Federation of Immunological Societies  (EFIS-IL)  for  a  research  visit  at  Biocruces  Bizkaia  Health  Research  Institute,  Barakaldo,  Spain.  VKK  received  an  EFIS-IL  short-term  research  fellowship  for  a  research  visit  at  King’s  College  London.  The research was funded by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) based at Guy's and St Thomas' NHS Foundation Trust and King's College London (IS-BRC-1215-20006) (SNK).  The  authors  acknowledge  support  by  the  Medical  Research  Council (MR/L023091/1) (SNK); Breast Cancer Now (147; KCL-BCN-Q3)(SNK); Cancer Research UK (C30122/A11527; C30122/A15774) (SNK); Cancer  Research  UK  King's  Health  Partners  Centre  at  King's  College  London   (C604/A25135)   (SNK);   CRUK/NIHR   in   England/DoH   for   Scotland,  Wales  and  Northern  Ireland  Experimental  Cancer  Medicine  Centre  (C10355/A15587)  (SNK).  The  views  expressed  are  those  of  the  author(s)  and  not  necessarily  those  of  the  NHS,  the  NIHR  or  the  Department  of  Health.  Additionally,  this  work  was  funded  by  Instituto  de  Salud  Carlos  III  through  the  project  \"PI16/01223\"  (Co-funded  by  European Regional Development Fund; “A way to make Europe”) to FB and  by  the  Department  of  Health,  Basque  Government  through  the  project “2019111031” to OZ. OZ is recipient of a Sara Borrell 2017 post-doctoral contract “CD17/00128” funded by Instituto de Salud Carlos III (Co-funded by European Social Fund; “Investing in your future”).","_id":"10836","month":"05","issue":"5","scopus_import":"1","publication_status":"published","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"date_created":"2022-03-08T11:19:05Z","external_id":{"pmid":["32990982"],"isi":["000577708800001"]},"volume":76,"department":[{"_id":"Bio"}],"publisher":"Wiley","pmid":1,"type":"journal_article","citation":{"apa":"Pranger, C. L., Singer, J., Köhler, V. K., Pali‐Schöll, I., Fiocchi, A., Karagiannis, S. N., … Jensen‐Jarolim, E. (2021). PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow’s milk allergy and tolerance. <i>Allergy</i>. Wiley. <a href=\"https://doi.org/10.1111/all.14604\">https://doi.org/10.1111/all.14604</a>","ieee":"C. L. Pranger <i>et al.</i>, “PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow’s milk allergy and tolerance,” <i>Allergy</i>, vol. 76, no. 5. Wiley, pp. 1553–1556, 2021.","ama":"Pranger CL, Singer J, Köhler VK, et al. PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow’s milk allergy and tolerance. <i>Allergy</i>. 2021;76(5):1553-1556. doi:<a href=\"https://doi.org/10.1111/all.14604\">10.1111/all.14604</a>","mla":"Pranger, Christina L., et al. “PIPE‐cloned Human IgE and IgG4 Antibodies: New Tools for Investigating Cow’s Milk Allergy and Tolerance.” <i>Allergy</i>, vol. 76, no. 5, Wiley, 2021, pp. 1553–56, doi:<a href=\"https://doi.org/10.1111/all.14604\">10.1111/all.14604</a>.","ista":"Pranger CL, Singer J, Köhler VK, Pali‐Schöll I, Fiocchi A, Karagiannis SN, Zenarruzabeitia O, Borrego F, Jensen‐Jarolim E. 2021. PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow’s milk allergy and tolerance. Allergy. 76(5), 1553–1556.","chicago":"Pranger, Christina L., Judit Singer, Verena K. Köhler, Isabella Pali‐Schöll, Alessandro Fiocchi, Sophia N. Karagiannis, Olatz Zenarruzabeitia, Francisco Borrego, and Erika Jensen‐Jarolim. “PIPE‐cloned Human IgE and IgG4 Antibodies: New Tools for Investigating Cow’s Milk Allergy and Tolerance.” <i>Allergy</i>. Wiley, 2021. <a href=\"https://doi.org/10.1111/all.14604\">https://doi.org/10.1111/all.14604</a>.","short":"C.L. Pranger, J. Singer, V.K. Köhler, I. Pali‐Schöll, A. Fiocchi, S.N. Karagiannis, O. Zenarruzabeitia, F. Borrego, E. Jensen‐Jarolim, Allergy 76 (2021) 1553–1556."},"quality_controlled":"1"},{"scopus_import":"1","month":"11","_id":"10301","external_id":{"isi":["000720945900001"]},"date_created":"2021-11-18T06:59:45Z","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"GaNo"}],"volume":10,"quality_controlled":"1","citation":{"short":"M.J. Conde-Dusman, P.N. Dey, Ó. Elía-Zudaire, L.E. Garcia Rabaneda, C. García-Lira, T. Grand, V. Briz, E.R. Velasco, R. Andero Galí, S. Niñerola, A. Barco, P. Paoletti, J.F. Wesseling, F. Gardoni, S.J. Tavalin, I. Perez-Otaño, ELife 10 (2021).","mla":"Conde-Dusman, María J., et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” <i>ELife</i>, vol. 10, e71575, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/elife.71575\">10.7554/elife.71575</a>.","ista":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, Garcia Rabaneda LE, García-Lira C, Grand T, Briz V, Velasco ER, Andero Galí R, Niñerola S, Barco A, Paoletti P, Wesseling JF, Gardoni F, Tavalin SJ, Perez-Otaño I. 2021. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 10, e71575.","chicago":"Conde-Dusman, María J, Partha N Dey, Óscar Elía-Zudaire, Luis E Garcia Rabaneda, Carmen García-Lira, Teddy Grand, Victor Briz, et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/elife.71575\">https://doi.org/10.7554/elife.71575</a>.","ama":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, et al. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/elife.71575\">10.7554/elife.71575</a>","apa":"Conde-Dusman, M. J., Dey, P. N., Elía-Zudaire, Ó., Garcia Rabaneda, L. E., García-Lira, C., Grand, T., … Perez-Otaño, I. (2021). Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.71575\">https://doi.org/10.7554/elife.71575</a>","ieee":"M. J. Conde-Dusman <i>et al.</i>, “Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021."},"abstract":[{"lang":"eng","text":"De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement."}],"type":"journal_article","has_accepted_license":"1","article_processing_charge":"No","file_date_updated":"2021-11-18T07:02:02Z","language":[{"iso":"eng"}],"status":"public","date_updated":"2024-10-21T06:02:05Z","author":[{"first_name":"María J","last_name":"Conde-Dusman","full_name":"Conde-Dusman, María J"},{"full_name":"Dey, Partha N","last_name":"Dey","first_name":"Partha N"},{"first_name":"Óscar","last_name":"Elía-Zudaire","full_name":"Elía-Zudaire, Óscar"},{"id":"33D1B084-F248-11E8-B48F-1D18A9856A87","last_name":"Garcia Rabaneda","full_name":"Garcia Rabaneda, Luis E","first_name":"Luis E"},{"full_name":"García-Lira, Carmen","last_name":"García-Lira","first_name":"Carmen"},{"first_name":"Teddy","full_name":"Grand, Teddy","last_name":"Grand"},{"full_name":"Briz, Victor","last_name":"Briz","first_name":"Victor"},{"first_name":"Eric R","last_name":"Velasco","full_name":"Velasco, Eric R"},{"last_name":"Andero Galí","full_name":"Andero Galí, Raül","first_name":"Raül"},{"first_name":"Sergio","full_name":"Niñerola, Sergio","last_name":"Niñerola"},{"last_name":"Barco","full_name":"Barco, Angel","first_name":"Angel"},{"first_name":"Pierre","full_name":"Paoletti, Pierre","last_name":"Paoletti"},{"first_name":"John F","full_name":"Wesseling, John F","last_name":"Wesseling"},{"first_name":"Fabrizio","last_name":"Gardoni","full_name":"Gardoni, Fabrizio"},{"first_name":"Steven J","full_name":"Tavalin, Steven J","last_name":"Tavalin"},{"last_name":"Perez-Otaño","full_name":"Perez-Otaño, Isabel","first_name":"Isabel"}],"title":"Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly","keyword":["general immunology and microbiology","general biochemistry","genetics and molecular biology","general medicine","general neuroscience"],"oa_version":"Published Version","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","isi":1,"publication":"eLife","acknowledgement":"We thank Stuart Lipton and Nobuki Nakanishi for providing the Grin3a knockout mice, Beverly Davidson for the AAV-caRheb, Jose Esteban for help with behavioral and biochemical experiments, and Noelia Campillo, Rebeca Martínez-Turrillas, and Ana Navarro for expert technical help. Work was funded by the UTE project CIMA; fellowships from the Fundación Tatiana Pérez de Guzmán el Bueno, FEBS, and IBRO (to M.J.C.D.), Generalitat Valenciana (to O.E.-Z.), Juan de la Cierva (to L.G.R.), FPI-MINECO (to E.R.V., to S.N.) and Intertalentum postdoctoral program (to V.B.); ANR (GluBrain3A) and ERC Advanced Grants (#693021) (to P.P.); Ramón y Cajal program RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077 FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637) and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R), Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence Awards (SEV-2013-0317, SEV-2017-0723).","year":"2021","article_type":"original","publication_identifier":{"issn":["2050-084X"]},"article_number":"e71575","date_published":"2021-11-17T00:00:00Z","intvolume":"        10","file":[{"relation":"main_file","checksum":"59318e9e41507cec83c2f4070e6ad540","content_type":"application/pdf","file_id":"10302","date_updated":"2021-11-18T07:02:02Z","access_level":"open_access","file_size":2477302,"creator":"lgarciar","file_name":"elife-71575-v1.pdf","date_created":"2021-11-18T07:02:02Z","success":1}],"oa":1,"day":"17","doi":"10.7554/elife.71575"}]