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B-different SIGNED

The RNA-Binding Protein ZFP36L1 regulates the terminal differentiation of B lymphocytes

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 B-different project word cloud

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scientist    gc    zfp36l1    dynamics    dictates    expertise    edge    rapid    me    commit    cutting    regulation    humoral    decision    transcriptome    lab    expression    rbp    data    post    differentiation    expand    secreting    germinal    vitro    elucidate    turn    highest    vaccines    fate    implications    antigen    largely    proteome    skills    expressing    pioneers    indicating    inhibits    binding    career    decisions    lymphocyte    immunoglobulin    governed    gene    strength    gcs    uniquely    mouse    dysfunctional    pc    transduction    unpublished    reveal    downstream    plasma    bioinformatics    proteins    cells    transcriptional    immunity    undergo    rna    unexplored    interplay    acquire    technologies    centre    host    cell    levels    antibodies    interactions    maturation    biochemical    regulator    unknown    signal    reaction    independent    function    models    stringent    employed    terminal    autoimmunity    guarantees    multidisciplinary    lymphomas    remodelling    mainly    defective    managerial    microenvironment    affinity   

Project "B-different" data sheet

The following table provides information about the project.

Coordinator
THE BABRAHAM INSTITUTE 

Organization address
address: Babraham Hall
city: CAMBRIDGE
postcode: CB22 3AT
website: www.babraham.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 212˙933 €
 EC max contribution 212˙933 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2020
 Duration (year-month-day) from 2020-09-01   to  2022-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE BABRAHAM INSTITUTE UK (CAMBRIDGE) coordinator 212˙933.00

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 Project 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.

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