Objective Antibodies secreted by B cells of the adaptive immune system establish an essential barrier against bacteria and viruses and their presence is the hallmark of protective vaccinations. B cells are licensed for their tasks during germinal center (GC) reactions and differentiation into antibody-secreting plasma cells. Unfortunately, B cell-derived autoantibodies and proinflammatory cytokines can cause or contribute to autoimmune diseases.While major transcription factor networks regulating protective (or pathogenic) GCB cell responses have been identified and characterized, little is known about the post-transcriptional regulation by RNA-binding proteins (RBP), whose number rivals that of transcription factors.We postulate that RBPs exercise critical post-transcriptional control over germinal center B (GCB) and plasmacytic cell physiology and we aim to identify and molecularly characterize these regulatory mechanisms.To this end, we will complement sophisticated genetic mouse models with novel cell culture systems. We will monitor RBP activity with fluorescent sensors and use proteomics to reveal RBPs regulating the protein abundance of critical mediators of GCB and plasmacytic cell fates. In addition, we will conduct genetic screens to uncover relevant functions of a short list of 40 RBPs, whose protein expression we found to differ significantly between GCB and mantle zone B cells. Ultimately, we will use cellular immunology and RNA biochemistry to elucidate how these RBPs exert their post-transcriptional control. Through the integrated power of our multi-disciplinary approach we will thus pinpoint and investigate the functions of key RBPs regulating the biology of GCB and plasmacytic cells. GCB-PRID promises to uncover profoundly new insights into post-transcriptional regulation of adaptive immunity. Thereby, this groundbreaking research aims to reveal novel molecular targets for the treatment of autoimmune diseases, whose incidence is steadily on the rise. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesbasic medicineimmunologyautoimmune diseasesmedical and health sciencesbasic medicinephysiologynatural sciencesbiological sciencesgeneticsRNA Keywords Germinal center B cell autoimmunity plasma cell RNA-binding protein post-transcriptional gene regulation Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-CoG-2015 - ERC Consolidator Grant Call for proposal ERC-2015-CoG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Host institution KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN Net EU contribution € 1 998 066,00 Address ISMANINGER STRASSE 22 81675 Muenchen Germany See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 998 066,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN Germany Net EU contribution € 1 998 066,00 Address ISMANINGER STRASSE 22 81675 Muenchen See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 998 066,00