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001     243042
005     20230214173929.0
024 7 _ |a G:(EU-Grant)101001613
|d 101001613
|2 CORDIS
024 7 _ |a G:(EU-Call)ERC-2020-COG
|d ERC-2020-COG
|2 CORDIS
024 7 _ |a corda__h2020::101001613
|2 originalID
035 _ _ |a G:(EU-Grant)101001613
150 _ _ |a Post-transcriptional and post-translational mechanisms underlying B cell selection by T cells in germinal centers
|y 2021-05-01 - 2026-04-30
372 _ _ |a ERC-2020-COG
|s 2021-05-01
|t 2026-04-30
450 _ _ |a PostTransGC
|w d
|y 2021-05-01 - 2026-04-30
510 1 _ |0 I:(DE-588b)5098525-5
|a European Union
|2 CORDIS
680 _ _ |a Enduring protection from pathogens and robust responses to vaccination depend on the generation of high-affinity antibodies through the germinal center (GC) reaction. In GCs, T helper cells promote the extensive proliferation of high-affinity B cell clones and their differentiation into plasma cells through cellular interactions that modulate gene expression. Here, we aim to unravel multiple post-gene expression mechanisms, including mRNA and protein stability regulation, that jointly control the outcome of T-B interactions in GCs. Since it is technically challenging to examine gene transcription and cellular contacts simultaneously, a method that links these two processes and measures transcription in-situ is required. To understand how T cell help controls gene expression dynamics and persistence of mRNA transcripts in GC B cells, we will use LN-smFISH, a new method we recently developed that combines imaging of individual cells and single mRNA transcripts within lymph nodes. Through in-vivo manipulation of B cells and co-visualization of single cells and mRNAs, we will define the dynamics of gene expression during T-B contacts and plasma cell generation in GCs (Aim1). Using our specialized in-vivo models, we will examine how modulation of mRNA stability and translation by transcript methylation controls B cell clonal expansion and define which genes are regulated by this machinery (Aim2). Finally, we will examine how the degradation of known and novel key proteins control gene networks and B cell fate in GCs (Aim3). Together, we envision the establishment of a unifying model for how sequential layers of regulation orchestrate the translation of T-B interactions to fate decisions. The findings may lead to improved vaccine strategies and expose new checkpoints for manipulation in autoimmune diseases and GC-derived lymphoma. On a broader scale, we expect to define new concepts about the role of mRNA and protein stability machineries under physiological conditions.
909 C O |o oai:juser.fz-juelich.de:899482
|p authority:GRANT
|p authority
909 C O |o oai:juser.fz-juelich.de:899482
980 _ _ |a G
980 _ _ |a CORDIS
980 _ _ |a AUTHORITY

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