Project description
Unravelling the mechanisms of B-cell development in germinal centers
Protection from pathogens and robust response to vaccination depends on the generation of high-affinity antibodies in the germinal centers (GCs). GCs are transiently formed lymph node structures where T helper cells promote the proliferation of high-affinity B-cell clones and their differentiation into plasma cells. The EU-funded PostTransGC project aims to unravel post-gene expression mechanisms that control T- and B-cell interactions in GCs. To understand T cells' control of gene expression dynamics and the persistence of mRNA transcripts in GC B cells, researchers will employ a recently developed method that combines imaging of individual cells and single mRNA transcripts within lymph nodes.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-COG - Consolidator Grant
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Call for proposal
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(opens in new window) ERC-2020-COG
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7610001 Rehovot
Israel
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