Decoding NK Cell Licensing Through Programmable Nanoscale Clustering and Spatial Mapping
Agency: Marie Curie
Type: HORIZON TMA MSCA Postdoctoral Fellowships - Global Fellowship
Principal Investigator: David Tomaz
Start-date: October 2026
End-date: September 2029
Grant Code: 101277416
DOI: 10.3030/101277416
Natural killer (NK) cells kill tumour and virus-infected cells without prior sensitisation. To do so safely they must first acquire functional competence, a process called licensing, and we still know little about how it works. NK_LIC2CLUSTER_SR1 tests whether the nanoscale clustering of inhibitory receptors encodes licensing. David Tomaz will use CRISPR knock-in of a chemically inducible Ly49A fusion in primary murine NK cells to cluster the receptor on demand, then measure the functional and signalling response in cells and after adoptive transfer into mice of defined MHC haplotypes. Single-molecule localisation microscopy will map Ly49A and phospho-SHP-1 across haplotypes, and the spatial measurements will be combined with the functional data to derive "licensing signatures" that predict NK cell competence.
This Global Fellowship runs for 36 months. The outgoing phase (months 1–24) takes place in the laboratory of Wayne Yokoyama at Washington University in St. Louis; the return phase (months 25–36) takes place in the Henriques laboratory at ITQB NOVA, the beneficiary, with Ricardo Henriques as supervisor.