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BASILIC SIGNED

Decoding at systems-level the crosstalk between the T cell antigen receptor, the CD28 costimulator and the PD-1 coinhibitor under physiological and pathological conditions.

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EC-Contrib. €

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 BASILIC project word cloud

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

inflammatory    ox40    decisions    severe    triggers    autistic    superfamily    pd    coinhibitor    pathogenic    optimal    favorable    places    ing    satisfying    comprehension    physiology    place    costimulators    ignored    ideal    nature    lat    think    receptor    stoichiometry    cell    coinhibitors    epigenomics    anti    scales    presenting    harmful    genetic    central    receptors    cells    malfunctions    capacity    cooperate    signaling    convey    positive    expansion    negative    experimental    multidisciplinary    costimulatory    sole    superseded    creates    straddling    clonal    stems    decode    immunopathologies    pay    tumoral    functions    addicted    methodology    primary    informations    organismal    although    lack    novelty    tcr    dynamics    disrupt    combining    levels    antigen    costimulator    largely    coinhibitory    fundamental    situation    crosstalk    cd28    molecular    integrate    informed    inputs    understand    tnfr    encounters    hub    signalosomes    proteomics    multiple    unveil    signals    isolation    tuned    architecture    probe    occupies    computational    plays   

Project "BASILIC" data sheet

The following table provides information about the project.

Coordinator
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS 

Organization address
address: RUE MICHEL ANGE 3
city: PARIS
postcode: 75794
website: www.cnrs.fr

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 France [FR]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-ADG
 Funding Scheme ERC-ADG
 Starting year 2018
 Duration (year-month-day) from 2018-08-01   to  2022-07-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS FR (PARIS) coordinator 2˙000˙000.00

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 Project objective

Although the T cell antigen receptor (TCR) occupies a central place in T cell physiology, it does not work in isolation and the signals it triggers are tuned by receptors that convey positive (costimulators) and negative (coinhibitors) informations. We lack a satisfying comprehension of the way T cells integrate such multiple inputs to make informed decisions. The proteomics-based methodology we developed around the TCR places us in a favorable situation to decode at systems-level the crosstalk between the TCR, the CD28 costimulator and the PD-1 coinhibitor signaling pathways. The novelty of our approach stems from (1) its use of primary T cells, (2) its capacity to probe the architecture and dynamics of signalosomes resulting from T cell-antigen presenting cell encounters, (3) the attention we pay to the stoichiometry of the studied signalosomes, a key parameter largely ignored in previous studies, and (4) its multidisciplinary nature straddling molecular and organismal scales. Our specific aims are: Aim 1. To understand how the TCR and CD28 signaling pathways cooperate to achieve optimal T cell responses. Aim 2. To determine whether CD28 is the sole target of the PD-1 coinhibitor. Aim 3. To determine how under inflammatory conditions CD28 functions can be superseded by those of OX40, a costimulator of the TNFR superfamily. Aim 4. To unveil how malfunctions of LAT, a key signaling hub used by the TCR, disrupt the TCR-CD28 crosstalk and result in unique pathogenic T cells that by becoming ‘autistic’ to TCR signals and addicted to CD28 signals lead to severe immunopathologies. We think that combining genetic, epigenomics, proteomics, and computational approaches creates ideal experimental conditions to understand at system-levels how TCR, costimulatory, coinhibitory and inflammatory signals are integrated during T cell clonal expansion. Although of fundamental nature, our project should help understanding the harmful role PD-1 plays during anti-tumoral responses.

 Publications

year authors and title journal last update
List of publications.
2019 Guillaume Voisinne, Kristof Kersse, Karima Chaoui, Liaoxun Lu, Julie Chaix, Lichen Zhang, Marisa Goncalves Menoita, Laura Girard, Youcef Ounoughene, Hui Wang, Odile Burlet-Schiltz, Hervé Luche, Frédéric Fiore, Marie Malissen, Anne Gonzalez de Peredo, Yinming Liang, Romain Roncagalli, Bernard Malissen
Quantitative interactomics in primary T cells unveils TCR signal diversification extent and dynamics
published pages: 1530-1541, ISSN: 1529-2908, DOI: 10.1038/s41590-019-0489-8
Nature Immunology 20/11 2020-04-24
2019 Javier Celis-Gutierrez, Peter Blattmann, Yunhao Zhai, Nicolas Jarmuzynski, Kilian Ruminski, Claude Grégoire, Youcef Ounoughene, Frédéric Fiore, Ruedi Aebersold, Romain Roncagalli, Matthias Gstaiger, Bernard Malissen
Quantitative Interactomics in Primary T Cells Provides a Rationale for Concomitant PD-1 and BTLA Coinhibitor Blockade in Cancer Immunotherapy
published pages: 3315-3330.e7, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2019.05.041
Cell Reports 27/11 2019-09-05

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