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ThymEForT

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Dissecting the role of thymic epithelial cells in T lymphocytes maturation duri...

Dissecting the role of thymic epithelial cells in T lymphocytes maturation during human foetal development The thymus plays an essential role in the establishment of adaptive immunity and central tolerance as it provides a nurturing environment for the differentiation of T cells, a process orchestrated by their interaction with multipl... ver más

05/01/2024

UNIVERSITY COLLEGE...

225K€

Presupuesto del proyecto: 225K€

Líder del proyecto

UNIVERSITY COLLEGE LONDON No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2024-01-05

MSCA-IF-2019: Individual Fellowships

I+D

Cerrada hace 5 años

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Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

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1 Participantes

UNIVERSITY COLLEGE LONDON

224.93K€ | Lider

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Duración del proyecto: 44 meses Fecha Inicio: 2020-04-06
Fecha Fin: 2024-01-05

Líder del proyecto

UNIVERSITY COLLEGE LONDON No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 225K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The thymus plays an essential role in the establishment of adaptive immunity and central tolerance as it provides a nurturing environment for the differentiation of T cells, a process orchestrated by their interaction with multiple cell types. Despite advances in the knowledge of human thymus, how it functionally develops during foetal life remains elusive. This project aims at dissecting molecular mechanisms responsible for functional maturation of T cells by recapitulating human foetal development within a novel in vitro 3D system. Stromal and T cell compartments will be isolated and characterised at relevant developmental stages before and after mature T cells appear to underpin when thymic stroma acquires competence to sustain T cell development. Stromal populations from relevant developmental stages will be expanded in vitro to be cocultured with T progenitors within a unique 3D thymic natural matrix developed by the host lab. Repopulated 3D scaffold is sliced according to clinical grade protocols and cultured, allowing to set up multiple coculture conditions with the same stroma and compare the output on T cell maturation. In parallel, foetal thymic epithelial cells will be genetically modified to determine the role of specific transcription factors important for T cells onset during development. Recently developed microfluidic devices will provide an additional layer of information regarding molecular mechanisms regulating the crosstalk between stromal and immunological compartments. I anticipate to recapitulate human T cell development within a novel, whole human 3D in vitro culture system, to tackle fundamental immunological questions regarding human thymus development including maturation of tolerogenic T cells and regulation of central tolerance. Last, new key molecular and cellular players for T-cell specification will be uncovered opening new avenues for both congenital immune deficiencies based upon correction of the underlying molecular defect.

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