We are proposing to develop an interdisciplinary project based on computational analysis of KIR receptors and in vitro experimental validation to study the role of autophagy in controlling the KIR activating and inhibitory receptors membrane expressions in NK cells and identify potential correlations between different KIR genotypes/autophagic responses and haematological malignancies.
O1 – To identify, by bioinformatics approaches, the KIR receptors that act as potential autophagic substrates and therefore whose membrane expressions may be chemically manipulated by inhibitory or activating modulators of autophagy.
O2 – Identify the KIR genotypes and/or allotypes. It includes both KIR genotyping and/or sequencing of regions corresponding to the amino-acid motifs involved in the interaction with autophagosomes (LIR – LC3 interacting region), providing information about various KIR allotypes.
O3 – Identify the correlations between different KIR genotypes/allotypes and autophagy responses in a healthy population.
O4 – Identify the possible differences in response to autophagy disturbance between NK cells from healthy persons (control group) and those collected from patients with haematological malignancies (eg, acute or chronic leukemias, T / NK or B cells lymphomas).
MO – Managerial objective.