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Control of T cell differentiation and plasticity through mitochondrial reprogramming

Project description

Mitochondria in T cell differentiation

T cells have a unique capacity to patrol the organism in search of pathogens or tumour antigens. Upon antigen recognition, T cells undergo rapid clonal expansion and differentiate into different types of effector cells. Funded by the Marie Skłodowska-Curie Actions programme, the REPROGRAMIT project is interested in the role of mitochondria in the differentiation and function of T cells in immune responses. Researchers will undertake a multidisciplinary approach to uncover the molecular mechanisms underlying mitochondrial function in T cell differentiation. They will investigate mitochondrial dynamics and explore the therapeutic potential of reprogramming mitochondrial function in T cell responses, potentially paving the way for new strategies to modulate immune responses against infection and cancer.

Objective

Mitochondria participate during the metabolic reprogramming of naive T cells. However, the molecular mechanisms by which mitochondria regulate T cell differentiation remain elusive. The project aims at revealing the mechanisms behind mitochondrial function and lineage specification and maintenance. Combining high-throughput analysis of gene expression and chromatin epigenetic status with biochemical, metabolic, cellular, and in vivo and in vitro approaches, we want to assess how mitochondria coordinate the metabolic status of the cell to transcriptional and epigenetic changes to control T cell differentiation and function in distinct inflammatory environments. For that our challenges are; (Obj.1) To investigate the role of mitochondrial dynamics in the metabolic reprogramming of T cell differentiation, (Obj.2) To study how metabolic pathways shape the transcriptional and epigenetic networks of the T cell lineages, (Obj.3) To identify mitochondria-to-nucleus signaling pathways that regulate T cell differentiation through modification of the transcriptional and epigenetic landscape, and (Obj.4) To investigate the therapeutic potential of reprogramming mitochondrial function in T cell responses against infection and cancer. REPROGRAMMIT will unveil significant breakthrough on (1) how mitochondria regulate the metabolic profiles of the distinct T cell subsets, (2) the identification of molecular candidates that reverse or modify T cell transcriptional programs through regulation of mitochondrial function, (3) the understanding on how nutrient availability and metabolic intermediates shape T cell differentiation and plasticity. In sum, REPROGRAMIT puts forward an ambitious and multidisciplinary but feasible program with the wide purpose of identifying novel checkpoints based on the crosstalk between mitochondria and the epigenome, with the final goal to modulate T cell immune responses against infection and cancer by reprogramming mitochondrial function.

Fields of science (EuroSciVoc)

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2017

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Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV
Net EU contribution

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.

€ 171 460,80
Address
HOFGARTENSTRASSE 8
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Research Organisations
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Total cost

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.

€ 171 460,80
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