Structure and function of the COMMD protein family.

In collaboration with Dr Fiona McDonald, University of Otago

The family of proteins known as the COMMD proteins are thought to be involved in carcinogenesis and tumour progression. As well as a general role in cancers associated with chronic inflammation through their interaction with the transcription factor NF‑κB, they may be specifically involved in prostate cancer progression and in some lymphomas. The aim of this project is to determine the atomic structures of these proteins in order to understand the way in which they function, and to structurally and functionally characterise macromolecular complexes of COMMD proteins interacting with NF-κB. Our long-term aim is to understand the molecular details of COMMD protein inhibition of NF-κB, with the aim of designing modulators of these interactions as therapeutic agents.

The Nedd4 family and SGK

In collaboration with Dr Fiona McDonald, University of Otago

The human epithelial sodium channel (ENaC) is vital for sodium and water homeostasis and the consequent regulation of blood pressure in the body. Proteins of the Nedd4 family contain multiple WW domains that mediate binding to the human ENaC, thereby regulating channel activity by the ubiquitination and subsequent endocytosis of the channel subunits. Their activity is thought to be mediated via the aldosterone-regulated kinase SGK1. We are interested in visualising these regulatory interactions at the atomic level, to understand how the channel is regulation in healath and disease.