The CAPSTONE consortium aims to develop small molecules that modulate presentation of tumour and self-antigens, as a novel immunotherapeutic approach. These molecules will target several aminopeptidases (ERAP and IRAP) that play a key role in peptide presentation by MHC class I molecules. The consortium will work to deepen our understanding of the cellular pathways implicating the enzymes, decipher enzyme dysfunction in diseases, and design and validate innovative selective therapeutic drugs. CAPSTONE will be a transdisciplinary state-of-the-art environment to train 15 Early-Stage Researchers. The consortium brings together a multidisciplinary group of researchers in medicinal chemistry, crystallography, cell biology, biomedicine, mass spectrometry, systems biology and bioinformatics, implicating academic institutions, industry and patient associations. CAPSTONE will prepare the ESRs for career perspectives in academia, the pharmaceutical industry, biotechnology SMEs, and provide them with scientific and transferable skills and high-value professional connections.
The selected candidate will study a panel of human leukaemia/lymphoma cells with functional ERAP1 to decipher the mechanism underlying the induction of NK cell-mediated anti-tumor responses resulting from ERAP1 inhibition. ERAP1 is known to regulate NK cell function by controlling the engagement of inhibitory receptors. This project will focus on generating CRISP/Cas9 ERAP KO leukaemia/lymphoma cells from patients expressing a functional ERAP gene to evaluate their ability to activate NK cells from healthy donors by functional assays. The most efficient tumor/NK cell combinations will be tested in vivo in NSG mice by adoptive transfer of NK cells and ERAP1 inhibitors. The candidate will collaborate with a fellow PhD student studying the function of ERAP aminopeptidases in the regulation of the tumor immune microenvironment.
Supervisor: Dr Doriana Fruci
Please apply through CAPSTONE website, selecting ESR#10
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