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T cells: Regulation of Original diversity And Diversification after activation (T cell ROAD)

Cel

T cell diversification during immune responses to infections or vaccines is key for combating an infection and the concomitant establishment of immune memory. This diversification is established phenotypically, functionally, transcriptionally and epigenetically. The ability of a cell to generate progeny with diverse fates is a general feature of stem cells and, as such, naïve as well as memory T cells have stem cell characteristics. At the core of this proposal is the key question of how - mechanistically - a naïve or memory mouse or human T cell generates progeny with different fates. We will address this key question from two complementary but also interconnected angles: First, we will investigate the role of established heterogeneity within the pool of naive CD8 T cells before activation. We recently uncovered cellular morphology coupled to distinct TCR signalling strength as a novel aspect of heterogeneity within naïve human and mouse T cells and could link this phenotype to differential fate adoption of their progeny after activation. We will now investigate this novel aspect of naïve T cell heterogeneity to unravel the mechanisms that instil and maintain these morphological differences in naïve T cells and how these differences confer altered TCR stimulation responsiveness. Second, we will study the mechanisms employed by CD8 T cells to generate diversity in response to antigen recognition and how these are interconnected to preceding naïve T cell heterogeneity. We will specifically interrogate the role and mechanism of asymmetric cell division (ACD) in T cell fate diversification upon TCR-mediated activation. These anticipated novel insights into T cell diversification mechanisms will not only deepen our knowledge of a fundamental biological process but will enable us to guide naive T cells in a tailored manner along their “T cell ROAD” - to improve T cell-based immunotherapeutic modalities for longer-lasting effects.

Dziedzina nauki (EuroSciVoc)

Słowa kluczowe

Program(-y)

Temat(-y)

System finansowania

HORIZON-ERC - HORIZON ERC Grants

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Zaproszenie do składania wniosków

(odnośnik otworzy się w nowym oknie) ERC-2025-ADG

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Instytucja przyjmująca

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Wkład UE netto
€ 2 500 000,00
Koszt całkowity
Brak danych

Beneficjenci (1)