Project description
An in vitro 3D model of thymus development
T cell differentiation in the thymus is central for adaptive immunity and central tolerance. However, the mechanism of thymus development during foetal life remains elusive. To dissect the mechanisms responsible for the functional maturation of T cells in the thymus, scientists of the EU-funded ThymEForT project will develop a novel in vitro 3D system that recapitulates the thymus at different developmental stages. Using a 3D scaffold seeded with stromal populations from relevant developmental stages and T cell progenitors, they will evaluate T cell maturation. Further work into the role of specific transcription factors will unveil key molecular players in T cell specification and help address fundamental immunological questions.
Objective
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.
Fields of science (EuroSciVoc)
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Keywords
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2019
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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.
WC1E 6BT London
United Kingdom
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.