Deciphering CTPS1 regulation during the immune response – CTP

Expansion and proliferation of antigen-specific T and B cells is a prerequisite for an effective immune response. We recently described a new combined immunodeficiency caused by mutations in CTPS1, a gene coding for CTP Synthetase 1 (CTPS1), an enzyme involved in the de novo synthesis of the CTP nucleotide. CTPS1 has a key role to sustain proliferation during the immune response. The aim of the project will be the study of the mechanism(s) of CTPS1 expression and its regulation in T cells in response to TCR activation: - First, the signaling pathways (downstream the TCR) leading to induction of CTPS1 expression in activated T lymphocytes will be examined. - secondly, in vivo regulation of CTPS1 expression in different mouse models will be studied during the development and activation of the immune system. - Finally, research of new regulatory elements important for T- cell proliferation function will be performed using genetic and functional approaches using immunodeficient patients.