Project description
Autoimmune disease pathogenesis and metabolic imprinting of CD4+T cells
Scientists identify around 80 autoimmune diseases that affect up to 9 % of the world's population. The IL-17-producing CD4+ T (Th17) cells are involved in autoimmune pathogenesis via recruitment to inflamed tissues. The Th17 cells are transcriptionally distinct in different tissues, and metabolic manipulation affects Th17 cells. Funded by the Marie Skłodowska-Curie Actions programme, the Th17 tissue metab project will use single-cell RNA sequencing and innovative metabolic analysis tools to identify a tissue metabolic switch for Th17 cell pathogenicity, testing the hypothesis that metabolic cues from the target tissue dictate Th17 phenotypes. The hits from this analysis will undergo further validation in a mouse autoimmune disease model for multiple sclerosis.
Objective
Autoimmune diseases affect an estimated 3-9% of the population and cause major personal and socio-economic consequences. IL-17-producing CD4+ T cells (Th17) are recruited to inflamed tissues and involved in autoimmune pathogenesis but were recently also shown to have homeostatic function in tissues. Preliminary data from the outgoing host indicate that Th17 cells are transcriptionally distinct in different tissues. How tissue Th17 cells acquire such specialized characteristics remains elusive. Based on recent findings from the lab that a metabolic manipulation affects Th17 cells, we hypothesize that metabolic cues from the target tissue dictate Th17 phenotypes. To address this, we will apply scRNAseq and the host lab developed Compass metabolic flux tool in 9 tissues. Hits from this analysis will undergo a novel screening approach, CHIME, to reveal effects on Th17 function. In autoimmunity, Th17 cells reside within different tissues before migrating to the inflamed tissue. Identifying a tissue metabolic switch for Th17 cell pathogenicity might thus pave the way for novel treatments. To study this, I will use a mouse model for the autoimmune disease multiple sclerosis (MS) for target validation. During the return phase, the findings will be set into context of tissue niche immunology and human biology. In healthy versus inflamed human tissue, spatial RNAseq will directly reveal metabolism related differences in a natural tissue niche context. The project will be performed in a world-renowned Th17 lab. The fellow brings extensive experience with tissue immune cell extractions and MS mouse models, enabling immediate project progression. The fellow will then bring back novel techniques and experience (scRNAseq, CHIME) to the return host, where she will acquire skills in human tissue niche immunology and spatial RNAseq. This project will enhance her expertise, research and transferable skills and allow to build a network to follow her goal of becoming an independent PI.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-GF - HORIZON TMA MSCA Postdoctoral Fellowships - Global Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2021-PF-01
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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.
97070 Wuerzburg
Germany
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