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Professor Barry Potter
Professor Barry Potter
Chemically designed molecules from Bath co-crystallized with a cell signalling protein that hydrolyses cADPR.
Chemically designed molecules from Bath co-crystallized with a cell signalling protein that hydrolyses cADPR.

Internal News - 02 April 2008

Major chemical biology grant links universities of Bath and Hamburg

More than £400,000 has been awarded to the universities of Bath and Hamburg to work on the molecules that act as messengers inside cells.

Professor Barry Potter from the Medicinal Chemistry Group in the Department of Pharmacy & Pharmacology has been awarded the grant to work in collaboration with Professor Andreas Guse from the University of Hamburg.

The grant, made by the Wellcome Trust, aims to study new nucleotide molecules that carry messages within cells, particularly in the T cells of the immune system.

The Bath group will chemically reconfigure the structures of signalling molecules, using synthetic organic chemistry in concert with computational chemistry techniques, to create new entities with potentially different and ‘tailor-made’ biological properties.

The Hamburg group will then evaluate the biological activities of these compounds and use them in investigative biology of cellular signalling pathways.

Professors Potter and Guse have had a long-standing collaboration over 12 years and have published extensively together in this area, but have never been funded together in such a major way.

While the work could potentially lead to new drug candidates and discover pathways for pharmacological intervention, its focus will be more upon investigating these fundamental new signalling pathways.

The design and discovery research is carried out in dedicated medicinal and biological chemistry laboratories at the University of Bath using state-of-the art technology.

“One of the current major challenges in the life sciences is to make synergistic use of many different individual disciplines to a common end: the understanding of biology in terms of chemistry,” said Professor Potter, Head of Medicinal Chemistry at Bath who will also work in collaboration with colleagues at the University of Oxford and at Cornell University, USA.

"Cellular signalling processes underpin a vast amount of modern biology.

“Designing ‘tailor-made’ chemical compounds that can interfere with cellular processes is a highly topical and important part of modern drug design that fits perfectly within the scientific mission of our department and the Medicinal Chemistry Group in particular.

“Such compounds are useful pharmacological tools for studying signalling pathways in cells and can expose novel pathways for drug design.

“Work such as this is only really possible through interdisciplinary collaboration between synthetic chemists, pharmacologists, computational chemists and X-ray crystallographers.

"Working closely with colleagues at Hamburg, Cornell and Oxford will allow us to maintain a strong reputation in the growing field of Chemical Biology, a challenging new area and one in which the Department of Pharmacy & Pharmacology has invested considerable strategic capital to encourage more such interactive partnerships between chemical and biological colleagues.

“Strong interdisciplinary collaborations between chemists and biologists are the key to future progress in the post-genomic world.

“However, success in such endeavours will not be achieved through the simple merging together of disparate scientists by managers, often in a purely cosmetic fashion and hoping for engineered synergy and interaction.

“What is much more critical is to find, stimulate and foster the right personal chemistry between individuals who can work together as equals and as real partners on such interdisciplinary endeavours. As in this case, these can easily be in different countries.”

"This is a grant of great potential for the University of Bath and further confirms its Department of Pharmacy & Pharmacology in the top rank of UK departments for chemistry applied to biology, supporting its standing as a department with a 5* research rating in the most recent Research Assessment Exercise, the highest possible.”

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Notes

The title of the grant is “Cyclic adenosine diphosphoribose (cADPR) and adenosine diphosphoribose (ADPR) analogues in human T-lymphocyte chemical biology.”

The Department of Pharmacy & Pharmacology at Bath celebrated its centenary earlier this year. Although the University of Bath is only 40 years old, the Department of Pharmacy & Pharmacology can trace its roots back to the Bath College of Chemistry & Pharmacy.

“Pharmacy in Bath has come a long way since the early days as a training college at the start of the 20th century,” said Professor Potter. “The Medicinal Chemistry activity here is particularly strong and cohesive, with research worth many millions of pounds and many young and talented staff.”

“We are now regarded as one of the leading pharmacy and pharmacology departments in the UK, top-ranked by both The Guardian and The Times newspapers. This present work is an example of the department’s large and cutting-edge portfolio of research.”

The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around £500 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.

Professor Guse is Head of the Calcium Signalling Group, Institute of Biochemistry and Molecular Biology I: Cellular Signal Transduction, Centre of Experimental Medicine, University Medical Center Hamburg-Eppendorf and Deputy Director. He is also Vice-Dean of Education in the Medical Faculty.

The work at Cornell with Dr Q Hao will concern determination of protein crystal structures in complex with molecules synthesised at Bath. The group has already solved several such structures together. Professor Potter has also worked for many years with Professor Galione of the Department of Pharmacology, Oxford University, where he is currently also Visiting Professor of Medicinal Chemistry, and this grant will provide an opportunity to further strengthen the Bath-Oxford link.