We recently reported a novel combined immunodeficiency in patients with loss of function mutations in the CTPS1 gene and characterized by high susceptibility to viral infection due to inability of T cell to proliferate and control infections. The project aims at acquiring fundamental knowledge on the biology of CTPS1, a key enzyme for the de-novo synthesis of CTP, including its role in embryonic development and in the immune system. Cellular and mouse models (including conditional KO and inducible KO) will be used to study the function and the regulation of CTPS1 under normal and pathological settings in the immune system. These studies will also help to determine whether CTPS1 could be a target for drugs to specifically dampen lymphocytes proliferation in autoimmune and inflammatory disorders. Chemical inhibitors of CTPS1 recently developed will be tested. The preliminary data already obtained by the team guarantee the workability of the project. This project relies on the complementary expertise of the four partners of the consortium.