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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

Explore the words cloud of the B-different project. It provides you a very rough idea of what is the project "B-different" about.

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   zfp36l1    germinal    technologies    cells    managerial    proteome    downstream    stringent    proteins    unpublished    multidisciplinary    binding    employed    reaction    terminal    rna    defective    inhibits    regulation    centre    elucidate    lymphocyte    gc   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

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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