Project description
Organelle ageing, organism ageing and dysfunctional T cell differentiation
T cells are essential to the adaptive immune system, protecting against infections and even cancer. Ageing impairs the maintenance of long-lived naive stem cells (cells in an inactivated, non-dividing state), whose attrition leads to a less diverse T cell population and the accumulation of ‘terminally differentiated’ T cells. This diminishes the immune response to threats. The ERC-funded DAMAGED project will investigate the hypothesis that the ‘aged’ pools of inherited mitochondria and peroxisomes – organelles with critical roles in cell metabolism – are related to dysfunctional T cell differentiation in ageing. Beyond insight into immunology, project research findings could have impact across multiple fields in relation to stem cell-based tissue regeneration.
Objective
Maintenance of long-lived and quiescent stem cells is impaired during ageing, which negatively impacts tissue regeneration by restricting cell diversity. In the context of T lymphocytes, ageing is linked to profound changes in their repertoire, which becomes less diverse due to naïve T cell attrition. This leads to the accumulation of terminally differentiated cells and results in poorer immune responses. I aim to understand whether T cell diversification is fostered by the unequal inheritance of heterogeneous pools of organelles with distinct chronological ages. I will focus on mitochondria and peroxisomes, as T cell metabolism is key to cell fate decisions. I hypothesize that i) organelle inheritance is influenced by early events following T cell activation, ii) organelle ageing leads to changes in trafficking and function and iii) the organelle repertoire can be manipulated to rejuvenate ageing T cells. To test these hypotheses, we will: (1) Investigate whether unequal inheritance of aged vs. young organelles is determined by pre-mitotic events and the consequences of perturbing organelle trafficking; (2) Dissect whether the role of organelle fission in regulating mitochondrial and peroxisomal dynamics discriminates organelles by age; (3) Develop tools to rejuvenate cells that accumulate damage and dysfunctional cargo by targeting organelle inheritance. All aims will address the potential reciprocal relationship between organismal ageing and organelle ageing as drivers of impaired T cell stemness. The focus on ageing relies on the potential to use any discovered modulation strategies in T cell therapies, being older adults particularly vulnerable to pathologies linked to immune and metabolic disorders. These findings will also have impact beyond the field of immunology, as organelle ageing is a general cell biological phenomenon and relevant across different stem-like cell types, which can have broader implications in the perspective of tissue regeneration.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
- natural sciences biological sciences cell biology cell metabolism
- medical and health sciences basic medicine immunology
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine gerontology
- medical and health sciences basic medicine physiology homeostasis
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.1.1 - European Research Council (ERC)
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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.
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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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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-STG
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4051 Basel
Switzerland
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