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TEC_Pro SIGNED

Molecular control of self-renewal and lineage specification in thymic epithelial cell progenitors in vivo.

Total Cost €

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EC-Contrib. €

0

Partnership

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 TEC_Pro project word cloud

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

cell    genetic    fate    mouse    genome    renewal    reporter    underlie    mice    transcriptomic    dissect    screen    fundamental    throughput    bipotent    diseases    responsible    cells    defects    depends    vaccines    elucidate    derive    vivo    components    organ    hematopoietic    codes    thymus    specifications    thymic    regulate    function    functionally    modern    organotypic    tec    autoimmunity    tolerant    mtecs    cellular    epithelial    treatment    teps    ctecs    divided    integrates    cancer    global    arise    immunology    sciences    assays    tecs    subtypes    niches    decisions    induction    tolerance    unsettled    cortical    ctec    health    self    infectious    pathogen    believe    understand    molecular    models    tools    antigens    immunity    generation    principles    combine    epigenetic    details    examine    medullary    lineage    programs    immunodeficiency    cultures    mtec    modulate    syndromes    responsive    rnai    place    inductive    progenitors    clonogenic    profiling    clinical    microenvironments    differentiation   

Project "TEC_Pro" data sheet

The following table provides information about the project.

Coordinator
INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR-IBMC 

Organization address
address: RUA ALFREDO ALLEN 208
city: PORTO
postcode: 4200 135
website: www.ibmc.up.pt

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 Portugal [PT]
 Total cost 1˙491˙749 €
 EC max contribution 1˙491˙749 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-07-01   to  2021-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUTO DE BIOLOGIA MOLECULAR E CELULAR-IBMC PT (PORTO) coordinator 1˙491˙749.00

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 Project objective

The development of vaccines for the treatment of infectious diseases, cancer and autoimmunity depends on our knowledge of T-cell differentiation. This proposal is focused on studying the thymus, the organ responsible for the generation of T cells that are responsive against pathogen-derived antigens, and yet tolerant to self. Within the thymus, thymic epithelial cells (TECs) provide key inductive microenvironments for the development and selection of T cells that arise from hematopoietic progenitors. As a result, defects in TEC differentiation cause syndromes that range from immunodeficiency to autoimmunity, which makes the study of TECs of fundamental, and clinical, importance to understand immunity and tolerance induction. TECs are divided into two functionally distinct cortical (cTECs) and medullary (mTECs) subtypes, which derive from common bipotent TEC progenitors (TEPs). Yet, the genetic and epigenetic details that control cTEC/mTEC lineage specifications from TEPs are unsettled. My objectives are to identify TEC progenitors and their niches within the thymus, define new molecular components involved in their self-renewal and lineage potential, and elucidate the epigenetic codes that regulate the genetic programs during cTEC/mTEC fate decisions. We take a global approach to examine TEC differentiation, which integrates the study of molecular processes taking place at cellular level and the analysis of in vivo mouse models. Using advanced research tools that combine reporter mice, clonogenic assays, organotypic cultures, high-throughput RNAi screen and genome-wide epigenetic and transcriptomic profiling, we will dissect the principles that underlie the self-renewal and lineage differentiation of TEC progenitors in vivo. I believe this project has the potential to contribute to one of the great challenges of modern immunology – modulate thymic function through the induction of TEPs - and therefore, represents a major advance in Health Sciences.

 Publications

year authors and title journal last update
List of publications.
2019 Maria Camila Trindade Ribeiro
Defining novel stages in medullary thymic epithelial cell differentiation: Implications for tolerance induction
published pages: , ISSN: , DOI:
UP repository 1 2020-04-01
2017 Brian M. Larsen, Avinash Bhandoola
A novel role for p53 in self-tolerance
published pages: 388-389, ISSN: 0006-4971, DOI: 10.1182/blood-2017-06-789115
Blood 130/4 2020-04-01
2016 Ana Rosalina Pereira Ribeiro
Unveiling thymic epithelial cell ontogeny: a roadmap to study the microenvironment for T-cell generation and tolerance
published pages: , ISSN: , DOI:
1 2020-04-01
2016 Nuno L. Alves, Ana R. Ribeiro
Thymus medulla under construction: Time and space oddities
published pages: 829-833, ISSN: 0014-2980, DOI: 10.1002/eji.201646329
European Journal of Immunology 46/4 2020-04-01
2018 Pedro Miguel Mendes Rodrigues
How to keep the thymus in shape: new molecular insights on thymic epitelial cell homeostasis and function
published pages: , ISSN: , DOI:
1 2020-04-01
2017 Pedro M. Rodrigues, Ana R. Ribeiro, Chiara Perrod, Jonathan J. M. Landry, Leonor Araújo, Isabel Pereira-Castro, Vladimir Benes, Alexandra Moreira, Helena Xavier-Ferreira, Catarina Meireles, Nuno L. Alves
Thymic epithelial cells require p53 to support their long-term function in thymopoiesis in mice
published pages: 478-488, ISSN: 0006-4971, DOI: 10.1182/blood-2016-12-758961
Blood 130/4 2020-04-01
2018 Pedro M. Rodrigues, Pärt Peterson, Nuno L. Alves
Setting Up the Perimeter of Tolerance: Insights into mTEC Physiology
published pages: 2-5, ISSN: 1471-4906, DOI: 10.1016/j.it.2017.11.001
Trends in Immunology 39/1 2020-04-01
2018 Helena Catarina Teixeira Meireles
Refining thymic epithelial cell differentiation: from progenitor cell isolation to the identification of discrete mature lineages
published pages: , ISSN: , DOI:
1 2020-04-01
2017 Catarina Meireles, Ana R. Ribeiro, Rute D. Pinto, Catarina Leitão, Pedro M. Rodrigues, Nuno L. Alves
Thymic crosstalk restrains the pool of cortical thymic epithelial cells with progenitor properties
published pages: 958-969, ISSN: 0014-2980, DOI: 10.1002/eji.201746922
European Journal of Immunology 47/6 2020-04-01
2018 Pedro M. Rodrigues, Ana R. Ribeiro, Nicolas Serafini, Catarina Meireles, James P. Di Santo, Nuno L. Alves
Intrathymic Deletion of IL-7 Reveals a Contribution of the Bone Marrow to Thymic Rebound Induced by Androgen Blockade
published pages: 1389-1398, ISSN: 0022-1767, DOI: 10.4049/jimmunol.1701112
The Journal of Immunology 200/4 2020-04-01

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