01 November 2004
"Mini genome project" seeks drug breakthrough
A major research project that raises hopes for much more effective drug treatments for diseases including cancers and parasitic, bacterial and viral diseases gets underway this week.
A research group at the University of Sheffield's Department of Molecular Biology and Biotechnology led by Professor Per Bullough is playing a key role in the Membrane Protein Structure Initiative consortium (MPSI), which Professor Bullough describes as "a mini human genome project".
Membrane proteins provide a number of functions essential for a healthy cell. About half the drugs in current use target membrane proteins, but so far designing new drugs has mostly been like playing a game of blind man's buff - we have simply been unable to see the target. The goal of MPSI is to finally visualise in detail many more membrane proteins that have the potential to be novel targets.
Professor Bullough explained, "Thanks to the human genome project we know the instructions that govern the structure of membrane proteins, but those instructions are written in code - we still know very little about the way that code is used to build a three dimensional shape. So this major collaborative project, involving some of the world's leading research groups in this field, aims to determine the proteins' shapes using a range of analytical methods. Following on from the human genome project it's one of the next big steps forward for novel drug treatments.
"At the moment the effectiveness of drugs that target membrane proteins is a totally hit and miss affair. But once we've discovered a protein's three-dimensional shape we have much more information to help us design a drug to bind on to it - creating a powerful drug which can cling to and modify its target protein really efficiently."
Examples of drugs that target membrane proteins are asthma drugs that bind to membrane proteins in the lung to open up the airways, antidepressants that alter proteins transporting brain chemicals across membranes, and anaesthetics that control opening and closing of channels across membranes in cells of the nervous system. Future targets for novel drugs might include, for example, membrane proteins that transport antibiotics across membranes and confer antibiotic resistance in bacteria.
The Membrane Protein Structure Initiative, a consortium of experienced membrane research groups at universities and institutes across the UK led by the University of Glasgow, is backed by funding worth £6.8m from the Biotechnology and Biological Sciences Research Council (BBSRC) - the largest grant yet awarded by the Council.
Professor Bullough's research group at the University of Sheffield will be tackling the "hard cases" among membrane protein samples - the ones whose structures the techniques used at the other research centres are unable to determine. Many membrane proteins are unstable outside their natural environment but, using advanced electron microscopy, the Sheffield team can mimic this natural environment and keep the proteins stable for long enough to be visualised.
Notes for Editors: Professor Per Bullough came to Sheffield University in 1996 after spending several years developing new techniques in electron microscopy and conducting research in membrane proteins involved in influenza infection. Prior to his arrival in Sheffield Professor Bullough was a researcher at Cambridge and Harvard Universities. He now leads a research team trying to exploit the new techniques to further understanding of membrane protein structure and function.
The Membrane Protein Structure Initiative is a consortium of membrane protein research groups from the Universities of Glasgow, Leeds, Manchester, Oxford, Sheffield, Imperial College, Birkbeck College and CCLRC Daresbury.
The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £300 million in a wide range of research that makes a significant contribution to the quality of life for UK citizens and supports a number of important industrial stakeholders including the agriculture, food, chemical, healthcare and pharmaceutical sectors. http://www.bbsrc.ac.uk
For further information please contact Jon Pyle, head of communications, on 0114 222 1038. or email j.pyle@sheffield.ac.uk.
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