Objective
CD8⁺ T cells are central to adaptive immunity, eradicating pathogens and tumours while sustaining immune homeostasis. Their fate is shaped not only by transcriptional and signalling programmes but also by organellar organisation, an emerging regulatory layer. The mitochondrial GTPase Optic Atrophy 1 (OPA1) is uniquely positioned within this layer. By controlling inner membrane fusion and the assembly of cristae junctions, it tunes mitochondrial function. OPA1 is regulated through alternative splicing and proteolytic cleavage, generating isoforms whose balance dictates mitochondrial and cellular outcomes. Mutations disrupting this balance underlie cellular and systemic dysfunction, including immunopathologies. Existing immunological knowledge derives almost exclusively from murine knockout models, which lack isoform diversity and the nuanced regulation of the human system. IMMUNOPA-8T addresses this critical gap through three integrated aims that together define how OPA1 regulation shapes human CD8⁺ T cell biology in health and disease.
Aim 1 will deliver the first molecular and ultrastructural atlas of OPA1 across human T cell proliferative trajectories, by integrating proteogenomic approaches with volumetric electron microscopy.
Aim 2 will establish a genetic manipulation platform to mechanistically dissect isoform- and cleavage-specific OPA1 functions, combining precise editing with functional, metabolic, and ultrastructural phenotyping.
Aim 3 will translate these insights into a disease context, profiling OPA1 status in post-transplant lymphoproliferative disease (PTLD) and applying mechanistic discoveries to engineer ultrastructurally optimised CAR-T cells targeting EBV-driven lymphoma.
By linking molecular regulation, ultrastructural organisation, and function, IMMUNOPA-8T aims to open a new dimension of human T cell biology and unlock novel avenues for therapeutic innovation.
Fields of science (EuroSciVoc)
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.
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.
- medical and health sciences medical biotechnology genetic engineering
- natural sciences biological sciences cell biology
- natural sciences physical sciences optics microscopy electron microscopy
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine physiology homeostasis
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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)
MAIN PROGRAMME
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2025-PF
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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.
4051 Basel
Switzerland
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.