I received my B.Sc in Pharmacology from the University of Bristol in 1997, before going on to undertake a Ph.D in the department of Medicine, also at the University of Bristol, under the supervision of Prof Craig McArdle, where I investigated the role of endocytosis in the function of the Gonadotropin Releasing Hormone Receptor. On completion of my PhD, I took a postdoctoral position at the University of California, San Francisco, where I continued my training in the laboratory of Prof Mark von Zastrow, a renowned leader in the field of endocytic trafficking in the function of G-protein-coupled receptors, where I investigated the role of Ubiquitin in endosomal trafficking. In 2011, I returned to the UK to work in the Gene Therapy Group at Imperial College London, in the laboratory of Prof Nicholas Mazarakis, where I studied how lentiviral vectors undergo trafficking within motor neurones. I was appointed Lecturer in Pharmacology at the University of Aberdeen in January 2013
My overall research involves investigating the mechanisms by which G-protein-coupled Receptors undergo endocytic trafficking and how this process influences receptor function and cellular signalling. G-protein coupled receptors (GPCRs), represent the largest family of cell surface receptors
and are the prime regulators of many physiological systems. Their undoubted importance is demonstrated by the fact that as many as 50% of marketed drugs target GPCRs. The signalling fidelity of GPCRs is maintained in part by a regulated trafficking process involving the removal of desensitised receptors by internalisation followed by either recycling to the plasma membrane (resensitisation) or targeting to the lysosome for downregulation. Although a great deal of progress has been made in understanding the processes underlying receptor endocytosis, including the critical role of receptor kinases and arrestin, comparatively little is known about the processes determining the postendocytic fate of GPCRs. My specific interests lie in how the levels of receptor are maintained or downregulated in the extended presence of agonist, and what mechanisms determine how receptors are sorted to the lysosome.
Fig.1 Simplified model of GPCR post-endocytic sorting. Following endocytosis GPCRs can undergo recycling to the plasma membrane (1) (possibly regulated by the retromer) or sorting to the lysosome. This can involve ubiquitin regulated sorting by the ESCRT complex (2), initial ubiquitin-indendent sorting (possibly by GASP) before ubiquitin and ESCRT mediated transfer to Intralumenal vesicles (3) or direct interaction with the ESCRT III component, independent of ubiquitination (4) mediated by ALIX.
I am currently investigating the role of ubiquitination in directing receptor translocation to intralumenal vesicles and its requirement or otherwise for trafficking to the lysosome. The images show a clear requirement for receptor (green) to be ubiquitinated or it remains on the endosome limiting membrane. However it is still able to undergo limited proteolysis with N-terminal fragments (red) being seen within the lumen of the endosome in some cases. This fragementation can be further visualised by Western blot (Henry et al, 2011).
I currently teach and run the Honours year undergraduates on the Molecular Pharmacology course (PA4005), and the lab based research course as part of the intercalated BSc Medical Sciences (Hons). I also lectiure on the Honours Advanced Molecular Biology (MB4050) as part of the dynamic cell module. I also teach Molecular Pharmacology on the Clinical Pharmacology MSc course (MT5024)