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Keeley Group

New molecular mechanisms underpinning integrated oxygen homeostasis

Oxygen homeostasis has been a constant challenge to life on earth for at least the last ~600 million years. A growing reliance on oxidative metabolism dramatically increased O2 demand, whilst multicellularity led to progressively more complicated distribution and supply. As a result, eukaryotes have evolved a number of complex oxygen homeostatic processes which, though often distinct in kinetics and mechanism, all operate as part of an integrated response to sense, adapt and overcome changes in oxygen availability. Our group is interested in identifying new oxygen homeostatic mechanisms, focusing on non-transcriptional reflex and compensatory responses to changes in oxygenation for which we still lack coherent molecular insight.

We use a variety of models to study this, ranging from biochemistry right through to whole animal physiology, and often consider the breadth of eukaryotic biology. This approach is exemplified in both areas of current focus in the lab:

(i)   N-terminal cysteine dioxygenation; an ancient form of oxygen sensing found widely across algae, plants and metazoans. Working with colleagues in the departments of Biology and Chemistry, we described the enzyme responsible for this process in mammals and are working to understand its physiological role in shaping the response to hypoxia.

(ii) Oxygen chemosensitivity in specialised cells; All animals exhibit a rapid, homeostatic reflex response to changes in arterial O2 levels, in which oxygen chemosensation is coupled to processes aimed at altering O2 supply and/or demand. We are working alongside the Bishop (DPAG) and Ratcliffe (NDM) labs to elucidate the underlying molecular physiology behind this process, and define its intra- and inter-organismal conservation.

We are always interested in hosting enthusiastic home and international students for undergraduate, M.Sc. and Ph.D./D.Phil. projects. Please get in touch at

thomas.keeley@dpag.ox.ac.uk.  

 

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