GCB-PRID
Financiado
Post transcriptional Regulation of Germinal Center B Cell Responses in Immunity...
Post transcriptional Regulation of Germinal Center B Cell Responses in Immunity and Disease
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 ge...
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.
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Duración del proyecto: 64 meses
Fecha Inicio: 2016-04-23
Fecha Fin: 2021-08-31
Fecha Fin: 2021-08-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2021-08-31
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-CoG-2015:
ERC Consolidator Grant
Cerrada
hace 9 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIV...
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Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
354.04K€ |
Participante