Project description
Molecular insight into T-cell homeostasis
Under physiological conditions, the T-cell compartment remains stable in terms of composition, indicating the presence of homeostatic mechanisms that regulate cell differentiation, survival and death. Characterising these mechanisms is important for understanding how the immune system functions in health and disease. Funded by the Marie Skłodowska-Curie Actions programme, the COR1-TCELL project will focus on the protein coronin 1, recently shown to be involved in T-cell balance. Using various laboratory techniques and genetic modification, researchers will dissect the molecular pathway of coronin 1. COR1-TCELL’s results will expand our understanding of T-cell regulation, offering potential insights into new therapeutic strategies including the design of CHIMERIC antigen receptor (CAR) T-cell immunotherapy.
Objective
Harnessing T-cell homeostasis is important for cancer immunotherapy as well as anti-microbial immunity and the prevention of autoimmune disorders. T-cell homeostasis in peripheral lymphoid organs is known to be regulated through interleukin-7-mediated cytokine signalling and via T-cell receptors recognising self-peptides loaded on major histocompatibility complex. However, recent results suggest a requirement of a third pathway at low T-cell density such as in newborns that depends on the WD repeat protein family member coronin 1, the mechanism of which is unknown. The objective of this proposal is to elucidate the molecular mechanism of coronin 1-dependent sensing of low cell density that contributes to peripheral T-cell homeostasis.
In preliminary work, I established a co-culture assay of T cells and antigen presenting cells that recapitulates coronin 1-dependent T-cell survival at low cell density. In addition, I found that adoptive transfer experiments reconstituted the coronin 1-dependent peripheral T-cell expansion in a lymphopenic environment in vivo. To delineate the molecular mechanisms underlying this cell density-dependent signalling mediated by coronin 1, I will combine the originally established in vitro and in vivo assay systems with state-of-the-art single-cell RNA sequencing, in addition to biochemical analysis utilising mass spectrometry. This will identify the signalling pathways and the molecules involved in this density-sensing mechanism. Finally, ad-hoc ablation of coronin 1 using a newly established inducible knockout mouse will reveal the role for coronin 1 in the maintenance of peripheral T cells after successful expansion at post-neonatal stage.
The results from this project will define a hitherto uncharacterized density-sensing pathway required for T-cell homeostasis. Furthermore, the fellowship will potentiate my career opportunities as it allows to explore cutting-edge biology and technologies in a highly stimulating research environment.
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 clinical medicine oncology
- natural sciences biological sciences genetics RNA
- medical and health sciences basic medicine immunology immunotherapy
- natural sciences chemical sciences analytical chemistry mass spectrometry
- medical and health sciences basic medicine physiology homeostasis
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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-EF-ST - Standard EF
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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-2017
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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.