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Microbiota-T cell interactions - antigen-specificity and regulation in health and disease

Objective

The microbiota has an enormous influence on human health. CD4+ T cells play a central role in controlling the interaction with the microbiota. By specifically reacting against individual microbial species, T cells enable a mutualistic co-existence with microbes. Inappropriate T cell responses against microbes are in turn associated with inflammatory diseases. Thus, the combination of T cell specificity and functionality form the key determinant for physiological versus pathological host-microbiota interactions. So far, research on T cell-microbiota interaction is almost exclusively focussed on functional T cell subsets, whereas antigen-specificity is rarely addressed. This is a significant roadblock for developing targeted therapeutic interventions for microbiota-associated diseases.
The interaction with the microbiota poses two particular challenges for adaptive immunity: first, the extremely high diversity of microbial species, and thus potential T cell targets; second, microbes are persistent and thus probably encountered chronically. Currently, we do not know (1) which microbes are targets of specific T cell reactivity in humans, (2) how the (chronic) interaction with the huge number of different microbial species is regulated by T cell specificity and function, and (3) how alterations of these parameters contribute to microbiota-associated diseases.
I developed a highly sensitive technology to detect and deeply characterize microbe-specific T cells directly from human samples. MicroT will identify microbial target species of human T cells and unravel the molecular mechanisms regulating chronic interaction of T cells with the highly diverse microbiota. I will define the impact of specific T cell-microbiota interactions on chronic inflammatory diseases and upon ageing. Answering these fundamental questions of microbiota-T cell interaction will identify specific immune or microbial targets as an essential basis for rational development of novel targeted therapies.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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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.

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2021-STG

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Host institution

UNIVERSITATSKLINIKUM SCHLESWIG-HOLSTEIN
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.

€ 1 500 000,00
Address
Ratzeburger Allee 160
23562 Lübeck
Germany

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Region
Schleswig-Holstein Schleswig-Holstein Lübeck, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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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.

€ 1 500 000,00

Beneficiaries (2)

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