Tom Keeley – Cell Biology 'Exploring cell autonomous oxygen homeostasis'

Oxygen homeostasis is a crucial and ubiquitous function of all eukaryotic cells, operating across a wide range of time scales and oxygen levels. Whilst specialised central and peripheral mechanisms control systemic arterial oxygen levels, this cannot provide localised or regional oxygen homeostasis. Transcriptional adaptations to hypoxia orchestrated largely by the hypoxia-inducible factors does occur ubiquitously, yet cannot provide rapid homeostatic control. This project will explore the role of a more recently described oxygen sensing pathway in mediating rapid and ubiquitous oxygen homeostasis. Coordinated by 2-aminoethanethiol dioxygenase (ADO) and the Cys branch of the N-degron pathway, this pathway controls the stability of regulators of G-protein signalling 4 and 5. State-of-the art molecular biological techniques will be employed to study how these proteins interact with the subcellular environment to affect cell autonomous oxygen homeostasis, focusing on control of mitochondrial function. Analysis of protein expression and location will be paired with functional readouts of cell physiology, including measurements of intracellular oxygen levels and second messenger signalling.