Project description
Natural killer immunology and receptor engineering for MHC-unrestricted immunotherapies
Natural killer (NK) cells kill tumour and virus-infected cells without prior sensitisation, but their clinical use is limited by the unclear mechanisms underlying their durable functional competence or ‘licensing’. Supported by the Marie Skłodowska-Curie Actions programme, the NK_LIC2CLUSTER_SR1 project will explore whether nanoscale clustering of inhibitory receptors encodes NK cell licensing, enabling the engineering of MHC-independent NK cells. It will assess whether clustering of Ly49A recruits phosphatases such as SHP-1 and creates licensing signatures that predict NK competence across MHC haplotypes. This work aims to advance MHC-unrestricted immunotherapies using insights from NK immunology and receptor engineering.
Objective
Natural killer (NK) cells are innate lymphocytes that kill tumor and virus-infected cells without prior sensitization, but clinical translation is hampered by limited mechanistic insight into how NKs attain durable functional competence or “licensing”.
NK_LIC2CLUSTER_SR1 will determine whether nanoscale clustering geometry of inhibitory receptors encodes licensing — a mechanistic insight that could enable engineering NK cells with predictable, MHC-independent, potency.
We will test whether ligand-independent clustering of the inhibitory receptor Ly49A recruits ITIM-associated phosphatases (e.g. SHP-1) and induces a licensing-like state in vivo, and whether quantitative nanoscale features (e.g. cluster size, density) form reproducible “licensing signatures” that predict NK competence across MHC haplotypes.
AIM 1 (causation): CRISPR knock-in of a chemically inducible Ly49A fusion at the Ncr1 locus in primary murine NKs will allow rapid, reversible clustering with a dimeriser. Functional (IFN-γ, CD107a, cytotoxicity, persistence, homing, tumor clearance) and mechanistic (ITIM phosphorylation, SHP-1 recruitment) readouts will be assessed ex vivo and after adoptive transfer into MHC-defined hosts.
AIM 2 (prediction & translation): Super-resolution imaging (SLML) and single-molecule mapping will quantify Ly49A and phospho-SHP-1 architectures across haplotypes. Spatial metrics will be integrated with functional data to derive reproducible licensing signatures and build predictive functional models.
The fellowship provides structured training and open-science outputs to accelerate fellow independence and maximise research impact. Leveraging worldwide expertise from the host labs in NK immunology, synthetic receptor engineering, advanced imaging, and computational modelling, the project will establish receptor topology as a mechanistic code for NK licensing, define nanoscale “licensing signatures,” and enable translational MHC-unrestricted immunotherapies.
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.
- natural sciences physical sciences optics microscopy super resolution microscopy
- medical and health sciences basic medicine immunology immunotherapy
You need to log in or register to use this function
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.
-
HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
See all projects funded under this programme
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-GF - HORIZON TMA MSCA Postdoctoral Fellowships - Global Fellowships
See all projects funded under this funding scheme
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
See all projects funded under this callCoordinator
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.
1099-085 Lisboa
Portugal
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.