My early fascination with protein signalling at membranes was fostered by my degree and doctoral studies with Prof Tim Levine (UCL, UK), where I studied phosphoinositide signalling. My interest in regulation of membrane proteins by proteases was catalysed by my postdoc with Prof Catherine Rabouille (Hubrecht Institute, NL). There, I discovered that cleavage of the tumour suppressor adhesion protein, E-cadherin, promoted epithelial extrusion - an initial stage of tumourigenesis. Since then, my major research focus has been the control of signalling and behaviour via proteolysis at membranes.

I subsequently moved to Prof Matthew Freeman’s lab (University of Oxford, UK) as a Marie Sklodowska-Curie fellow. There I discovered unexpected roles for the pseudoprotease iRhom2 in the regulation of the metalloprotease TACE/ADAM17, which triggers the release of the inflammatory cytokine, TNF, and many EGFR ligands. I also designed a screen to identify substrates of the rhomboid intramembrane protease, RHBDL2, and found that it cleaves the calcium channel Orai1. This process is critical to the control of immunological signalling.

Overall, my research indicates that polytopic proteins, e.g. ion channels such as Orai1, may be common targets for intramembrane proteases, and that intramembrane proteases can recognise specific conformational states in their substrates.

The approaches that I developed have paved the way for discovery of intramembrane protease substrates more generally, which I aim to capitalise upon during my Sir Henry Dale Fellowship at the School of Biochemistry, University of Bristol. Many of these proteases are enriched in neurons, so I aim to capitalise on the strong neuroscience research carried out here in Bristol.