As an undergraduate I studied biochemistry at the University of Bristol (1982-1985) and it was at this stage that my fascination grew for integral membrane proteins and how they achieve vectorial transport and how receptors signal across the membrane. I subsequently joined Mike Tanner’s group at Bristol for my PhD on the cloning of erythrocyte membrane proteins (1985-1989). My first postdoc was at the Biochemistry department at the University of Cambridge in the laboratory of Peter Henderson where I studied an unusual 10-helix sugar transporter for L-rhamnose. After being awarded a Research Fellowship at Girton College, Cambridge, I moved to the Laboratory of Molecular Biology in 1992 to work in the laboratory of Richard Henderson, specifically to do structural work on membrane transport proteins. The initial work was on the cocaine-sensitive serotonin transporter (SERT) and this later expanded to include the multidrug transporter EmrE, after being awarded an MRC Career Development Award, which then developed into a tenured research position. Working with EmrE, which is very stable in detergent, and with SERT, which is very unstable, convinced me of the advantages of having a generic process for the thermostabilisation of membrane proteins to facilitate structure determination. We subsequenelty developed techniques to thermostabilise G protein-coupled receptors in specific conformations by scanning mutagenesis coupled to thermostability assays. This culminated in the structure determination of the b1
-adenergic receptor. The technology we developed for the thermosabilisation of GPCRs was used as the basis to form Heptares Therapeutics Ltd in 2007, with the goal of developing candidate drugs through an understanding of GPCR structures. My own research continues at the LMB with the aim of understanding the function of GPCRs and transporters by elucidating conformational changes upon ligand and substrate binding.