Department of Biochemistry University of Oxford Department of Biochemistry
University of Oxford
South Parks Road
Oxford OX1 3QU

Tel: +44 (0)1865 613200
Fax: +44 (0)1865 613201
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Knowledge and skills exchange stimulated by new BBSRC-funded programme

A project which provides an opportunity for academia and industry to exchange ideas is about to get underway thanks to funding secured by University Lecturer Dr Phil Biggin.

Predicted binding mode of Evotec’s potent Histamine H3 G-protein biased antagonist (G-protein in yellow and β<sub>2</sub>-arrestin in green)

Predicted binding mode of Evotec’s potent Histamine H3 G-protein biased antagonist (G-protein in yellow and β2-arrestin in green) (Click to enlarge)

The BBSRC-funded Flexible Interchange Programme (FLIP) grant will enable a researcher from industry to spend some of their time in Dr Biggin’s lab. Together, the pair will use their complementary knowledge and experience to develop a methodology that has the potential to design better drugs with reduced side-effects.

The timely project revolves around G-protein coupled receptors (GPCRs), a major class of membrane proteins that accounts for around a half of drug targets today. Researchers have recently described a phenomenon called ‘biased signalling’ where the receptors can elicit a different signalling pathway depending upon the type of ligand that binds to them.

Dr Biggin will be working with Dr Alexander Heifetz from the drug discovery company Evotec to explore what controls the bias and activates one pathway in preference to another. Dr Heifetz will bring in GPCR expertise whilst Dr Biggin has molecular dynamics expertise in modelling the different functional states of GPCRs.

The researchers aim to build on previous success with computational modelling of GPCRs and combine those techniques with advanced molecular dynamics simulations. They will then apply the resulting tools to predict the nature of bias for compounds against new GPCR targets. Ultimately, the goal is to identify compounds that activate a specific signalling pathway, thereby reducing the possibility of side-effects.

By providing Dr Heifetz with funds to spend half his time over the next two years in Dr Biggin’s lab, the grant will have benefits to both sides. Dr Heifetz will have the freedom to develop his ideas in an academic environment whilst lab members will have the opportunity to interact with a very experienced scientist from industry who has a strong record in generating novel IP.

With an industrial scientist embedded in the lab for a period of time, there is scope for extensive knowledge transfer. Results generated by the project can be immediately applied within both an academic and industrial setting. The project will also provide an opportunity to stimulate the generation of new networks and partnerships to promote current GPCR research and its applications within drug discovery.

Evotec already has an active collaborative programme involving Dr Biggin, Dr Heifetz and structural biology groups. The FLIP project will contribute to this consortium whose current effort is to rationalise the design of crystallographic constructs for new GPCR targets. In addition to the expertise Evotec brings to the project, it will also provide technical resources in the form of computational chemistry software and screening expertise.

Dr Biggin said: ‘I am absolutely delighted to have this opportunity to extend our collaboration with Dr Heifetz in this way. There is huge scope for exchange of knowledge and the chance to make a distinct and exciting contribution to the drug-discovery effort around GPCRs.’

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