Investigating the role of a nutrient-dependent protein hydroxylase in cell polarity

Protein hydroxylation is generally catalysed by a family of oxygenases that depend on important nutrients and metabolites for activity, including; oxygen, Fe(II), ascorbate, and 2- oxoglutarate (2OG). As such, these '2OG-oxygenases' sit at the intersection of nutrient availability and metabolism where they can sense co-factor abundance to regulate a variety of critical cellular processes.

The 2OG-oxygenase family can be sub-divided into groups that share common functions, including the HIF prolyl hydroxylases, collagen hydroxylases, TET enzymes, and JmjC histone demethylases. These groups are generally localised to specific subcellular compartments where they perform dedicated biochemical reactions including hydroxylation and demethylation. Despite this apparent functional diversity, common themes are emerging, including the frequent regulation of gene expression by these enzymes. However, many 2OG-oxygenases remain completely or at least poorly characterised.
Our recent work has focussed on understanding the apparently complex roles of these and related protein hydroxylases in cell biology. Here, in this PhD project, we aim to understand the previously unexplored functions of poorly characterised 2OG-oxygenases, and their newly identified substrates, in fundamental cellular processes.