Structural Studies on Viruses, Viral Proteins and Cell Interactions

病毒的数量超过了地球上所有其他生物。这些纳米寄生虫在我们的细胞内繁殖，所以它们通常很难被消灭。约有3 300万人感染了艾滋病毒，许多其他人类病毒也对人类健康产生可怕的影响。病毒包括数百种主要的人类病原体，每年造成数百万人死亡。然而，这些疾病中的许多在原则上是可以预防或治疗的——天花在1979年被宣布根除，今年或明年，联合国粮农组织可能会宣布全球根除牛瘟，牛瘟是一种对分趾动物的毁灭性祸害。这是令人鼓舞的，并表明密切相关的麻疹病毒也可能屈服于协调一致的疫苗接种运动。尽管取得了这些成功，但仍有许多病毒无法通过接种疫苗加以控制。药物在治疗已经感染的人方面起补充作用。制药和生物技术行业为抗病毒研究和开发投入了大量资金，目前可用于对抗艾滋病毒的药物范围表明，这种策略可能非常有效。然而，意外出现的SARS和猪？流感表明，我们无法预测下一次重大病毒爆发，因此支持基础研究是明智的——为应对意外情况做好更好的准备。这项基础研究的建议来自牛津大学纳菲尔德医学系医学研究委员会教授大卫·斯图尔特。这项工作将以原子细节肖像的形式提供有关病毒的新信息，这些信息将在公共数据库中免费提供，供药物和疫苗设计方面的学术或商业专家使用。我们认为，这方面的知识最终很有可能让我们设计出更安全、更强大的疫苗。这项工作只能使用英国同步加速器“钻石”提供的非常明亮的x射线束，使我们能够看到这些通过普通显微镜看不见的粒子。这项工作的第一个目标是改进实验技术，以促进从病原体收集数据，然后调查对全球健康造成重大负担的几种病毒，包括三种主要的甲型、乙型和丙型肝炎病毒。对于一些较简单的病毒，我们将看看是否可以利用结构知识来指导改进疫苗的开发。

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.