Podcast on “GPCR crystal structures and drug discovery”

NeuropharmacologyNeuropharmacology

Podcast on “GPCR crystal structures and drug discovery”

Moderator 
Rod Hubbard, University of York and Vernalis Ltd, UK

Speakers 
Fiona Marshall, Heptares Therapeutics, UK
Chris Tate, University of Cambridge, UK

Listen to the podcast now >>

Download the full transcript >>

For more information on related program topics visit the 20th Neuropharmacology Conference website

Biography Rod Hubbard

Rod HubbardRod Hubbard has spent his entire academic career at the University of York. During the 1980s, he developed and applied methods in molecular graphics and modelling. Through the 1990's he helped to build and directed the York Structural Biology Laboratory, studying the structure and function of many classes of proteins, some of which were important therapeutic targets.

Since 2001, he has spent varying amounts of his time with the company, Vernalis, where he helped establish structure and fragment-based drug discovery. He has also acted as Chairman of various BBSRC committees and acts as a consultant to a number of pharmaceutical and biotechnology companies.

Biography Fiona Marshall

Fiona MarshallDr Marshall is a co-founder and Chief Scientific officer of Heptares Therapeutics Ltd a GPCR drug discovery company utilizing a novel structure based drug discovery approach utilizing stabilized receptors (StaRs). She has a BSc in Biochemistry from Bath University and a PhD in Neuroscience from Cambridge. She has over 20 years experience in Drug Discovery (GSK and Millenium Pharmaceuticals) with particular expertise on GPCRs. She has published extensively in the areas of GPCR heterodimerization, de-orphanization and more recently on GPCR structure based drug discovery.

Biography Chris Tate

Tate ChrisAs 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.