ESR Application form

ESR 10: In vivo anti-tumour safety and efficacy of NK cell-based immunotherapeutic approach in preclinical models

Recruiting Institution: Ospedale Pediatrico Bambino Gesù, IT PhD institution: Università di Roma, IT	Supervisor: Dr. Doriana Fruci
Project Description An ESR position is available to work on a translational research project focused on understanding how modulation of antigen processing can be exploited to induce anti-tumor efficacy of NK cell-based immunotherapeutic treatment for cancer in the environment of the Oncohaematology Research Centre at the Ospedale Pediatrico Bambino Gesù (OPBG) in Rome, Italy. The research centre offers a multidisciplinary working environment focused on immunology, oncohematology and molecular biology in a fully equipped research facility with high-tech systems supporting genomics, metagenomics, proteomics, microarray technology, flow cytometry and cell sorting, mass cytometry, cell and molecular biology, fluorescence microscopy and 3D high-throughput imaging. OPBG has established agreements with animal facilities located near the Hospital. The ESR will work in the team led by D. Fruci interested in understanding whether modulation of antigen processing can be exploited to induce effective anti-tumor immune responses. 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.
Essential Background: training in immunology and molecular and cellular biology.	Desirable Background: training in vivo biology, 3D flow cytometry, cell imaging.
Local Requirements:
Planned Secondments: Academic to University of Southampton (UK) 3M, to learn their in vivo functional assays to evaluate the effect of ERAP1 inhibitors; Industrial to Inocure, (Praha, CZ) 2M, for training on Drug delivery systems for in vivo applications.
Planned Starting Date: 1^st Oct. 2021	Application Deadline 5^th Apr 2021