Defining the physiology and therapeutic potential of oxygenases as signalling enzymes

The joint programme aims to link biochemical, physiological and medical perspectives to better define the potential of human 2-oxoglutarate-dependent (2-OG) dioxygenases as therapeutic targets. Both scientists have established track records in relevant fields: Professor Ratcliffe in the discovery and elucidation of physiological pathways that control gene expression in accordance with cellular oxygen levels, and Professor Schofield in the biochemistry and structural analysis of 2-OG oxygenases that catalyse diverse biological oxidations. Their work came together with their joint discovery of a set of 2-OG oxygenases that transduce oxygen-sensitive signals through oxygen-dependent hydroxylation of the transcription factor, hypoxia-inducible factor. From these discoveries, their joint goal is to continue to explore the wider potential of the 2-OG oxygenases as signalling vectors. This will include studying how they react under hypoxic, metabolic and related stresses, and defining the potential for therapeutic targeting in the many human diseases that are characterised by hypoxia and dysregulated metabolism.