Project description
Post-transcriptional control of gene expression in B cells
Long-lived immunity relies partly on antibodies which are secreted by plasma cells. The latter differentiate from selected B cells, which secrete high-affinity antibodies. This maturation process takes place in germinal centres (GCs) in secondary lymphoid tissues and necessitates changes at the transcriptional and protein levels. The scope of the EU-funded B-different project is to understand the post-transcriptional control of gene expression during B cell differentiation. Researchers will focus on the role of the RNA-binding protein ZFP36L1 in the process of B cell fate decision. Results will provide fundamental knowledge on humoral immunity and may improve our understanding of autoimmune disorders.
Objective
Plasma cells (PC) secreting high-affinity antibodies are key for long-term immunity and the success of vaccines. PC are mainly generated within the germinal centre (GC), a microenvironment where B cells undergo affinity maturation and selection. The GC reaction guarantees that only B cells expressing immunoglobulin with the highest affinity for the antigen will commit to terminal differentiation. Stringent regulation is essential, as dysfunctional GC B cells can cause defective immunity, autoimmunity, or B-cell lymphomas.
Affinity maturation requires rapid changes in the B cell transcriptome and proteome to enable cell fate decisions. This is governed by the interplay of signal transduction pathways and regulation at transcriptional and post-transcriptional levels. Post-transcriptional control is key for rapid remodelling of gene expression, yet its role in terminal differentiation remains largely unexplored. The host lab pioneers the study of RNA-binding proteins (RBP) in lymphocyte development and has unpublished data indicating that the RBP ZFP36L1 inhibits terminal differentiation of B cells in vitro. The regulation and function of ZFP36L1 in GCs is however unknown.
In this proposal I will build on the unique and multidisciplinary expertise of the host lab and my experience on post-transcriptional regulation and immunity to address how ZFP36L1 dictates fate decision of B cells. Uniquely available mouse models will allow me to study how signal strength and signal transduction control ZFP36L1 activity and its downstream implications for humoral immunity. Cutting-edge technologies will be employed to elucidate the dynamics of ZFP36L1-RNA interactions and how they in turn define the proteome and fate of GC B cells.
This work will reveal the role of an important new regulator of PC differentiation, and will enable me to expand my knowledge, acquire new biochemical, bioinformatics and managerial skills, and facilitate my career development as an independent scientist.
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 proteomics
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
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Keywords
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.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
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.
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.
Funding Scheme
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
CB22 3AT Cambridge
United Kingdom
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.