The role of Factor Inhibiting HIF (FIH) in T lymphocyte fate determination. (360G-Wellcome-211143_Z_18_Z)

Oxygen is essential for almost all animal life on the planet, acting as a key player in the energy production in cells. Cells are able to adapt to low oxygen environments by activating a factor named hypoxia-inducible factor (HIF), which shifts the metabolism of cells away from oxygen-consuming processes while increasing alternative energy-producing pathways. In T cells, an important type of immune cell involved in the body’s defence against infections and tumours, this metabolic shift alters cell function, resulting in a more aggressive immune response. Understanding how this process is regulated may allow us to target and harness immune cells to treat a variety of diseases, such as autoimmune disease or cancer. Our group and others have shown that boosting HIF levels in T cells makes them more effective in clearing tumours and resolving viral infections. We have also studied the effect of factor inhibiting HIF 1-alpha (FIH), a protein that blocks HIF activity. Interestingly, FIH itself also appears to alter the metabolism of cells, although its effect on immune cells is currently unknown. During my PhD I will assess the role of FIH in mouse T cells, focussing on how FIH-driven metabolic changes can augment immune responses.