Signalling pathways that control T cell metabolism and T cell fate (360G-Wellcome-205023_Z_16_Z)

The laboratory will map how antigen receptor, cytokine and environmental signals integrate to control the function of T lymphocytes. We will comprehensively define signaling pathways that maintain T cell metabolism, transcriptional and proteomic landscapes. Specifically, we will comprehensively delineate the molecular details of how changing the supply of oxygen, glucose and iron impact on T cell signal transduction pathways and T cell phenotype. We will explore the ability of the Prolyl hydroxylase domain protein PHD2 and the transcription factor NFIL3 to link oxygen sensing to the control of T cell function. We will define how glucose fueled signaling pathways including those mediated by AMP-activated Protein Kinase alpha1 (AMPKa1) and the O-GlcNAc transferase (OGT) control T cell fate. We will comprehensively map how the protein tyrosine phosphatases SHP-1 and SHP-2 regulate protein phosphorylation networks in T cells and how they modulate T cell proteomes and T cell function. We will also characterize signaling pathways mediated by Phosphatidylinositol 3,4,5-trisphosphate PI-3,4,5-P(3) and define how the lipid phosphatases PTEN and SHIP1 shape T cell metabolism and T cell function. These experiments will map and define the molecular processes that determine T cell fate outcomes.