Structural Studies on Viruses, Viral Proteins and Cell Interactions

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Viruses outnumber all other organisms on the globe. These nano-parasites reproduce inside our cells, so they are often very difficult to combat. Some 33 million people are infected with HIV and many other human viruses also have a terrible impact on human health. Viruses include hundreds of major human pathogens and are responsible for millions of deaths every year. Nevertheless many of these diseases can in principle be prevented or treated - smallpox was declared eradicated in 1979 and this year or next the United Nations Food and Agriculture Organisation is likely to declare the global eradication of rinderpest, a devastating scourge of cloven footed animals. This is encouraging and suggests that the closely related measles virus might also succumb to a concerted vaccination campaign. Despite these successes there are still many viruses which we are unable to control by vaccination. Drugs play a complementary role, for treating people already infected. The pharmaceutical and biotechnology industries pump considerable money into anti-viral research and development and the range of drugs now available to combat HIV shows that this strategy can be very effective. However the unexpected emergence of SARS and swine ?flu shows that we cannot predict the next major virus outbreak so it is sensible to support basic research - to be better prepared to respond to the unexpected. This proposal for such underpinning research comes from David Stuart, a Medical Research Council Professor based at the Nuffield Department of Medicine at Oxford University. The work will deliver new information about viruses, in the form of portraits in atomic detail, made freely available in public databases for use by academic or commercial experts in drug and vaccine design. We think that there is a real chance that this knowledge will eventually allow safer and more robust vaccines to be designed. This work is only possible using the very bright X-ray beams provided by the UK synchrotron, Diamond, allowing us to see these particles that are invisible through a normal microscope. The first aim of the work is to improve the experimental technology to facilitate data collection from pathogens and then to investigate several viruses which represent major burdens on global health, including the three major hepatitis viruses A, B and C. For some of the simpler viruses we will see if structural knowledge can be used to guide the development of improved vaccines.