The structure and function of nematode pathogenicity islands

寄生线虫是地球上数量最多的寄生虫之一--动物和植物感染它们是正常的。线虫感染了地球上大约四分之一的人，主要是发展中国家的年轻人和穷人。它们也是家畜的重要寄生虫，肉类、牛奶、羊毛等的持续生产需要控制这些寄生虫。尽管这些寄生虫无处不在，也很重要，但我们不知道它们如何危害宿主。具体地说，我们不知道它们用什么基因生活在宿主体内并以它们为食，但最终伤害宿主的是这一点。如果我们更多地了解这些基因，我们就可以更好地预测这些基因可能如何进化，我们就可以思考更好地控制这些寄生虫的新方法，这是我们保护人类和动物健康以及确保食品生产所必需的。我们发现了12组集中的基因，我们认为这些基因可以控制寄生性线虫的感染。查看我们的试验数据，我们发现这些基因组在不同的个体蠕虫之间有很大的差异，我们认为这是一个很好的迹象，表明蠕虫正在使用这些基因组在宿主内部相互竞争，这种竞争正在推动这些寄生虫对宿主造成的伤害。我们现在提议更详细地研究这些基因组，非常准确地了解它们在单个蠕虫之间的差异，并看看不同的基因类型是否自然地在宿主内一起出现。通过观察基因序列，我们还将预测哪些蠕虫在感染宿主的方式上应该是最不同的，然后我们将在实验室动物的实验中进行测试。通过这种方式，我们的工作将从仅仅比较基因序列转向测试线虫实际上是如何感染宿主的。我们将在一种名为圆线虫的线虫身上研究这一点，这种线虫在英国自然会感染老鼠，但我们也可以在实验室进行研究。通过测试我们的IDE，我们将确定是否已经发现了寄生线虫用来感染宿主的基因集。如果是这样的话，这就开启了对线虫如何感染并对宿主造成伤害的全新理解，然后可以用来更好地了解、预测和治疗未来的这些感染。

Parasitic nematode worms are some of the most abundant parasites on the planet - it is normal for animals and plants to be infected with them. Nematode worms infect about a quarter of people on the planet, mainly the young and poor in the developing world. They are also important parasites of livestock, and continued production of meat, milk, wool etc. requires controlling these parasites.Despite the ubiquity and importance of these parasites, we don't understand how they harm their hosts. Specifically, we don't understand what genes they use to live inside their hosts and to feed on them, but it is this which ultimately harms hosts. If we understand more about these genes we could better predict how these might evolve and we could think about new ways to better control these parasites, which we need to do to protect human and animal health, and to secure food production.We have discovered 12 concentrated sets of genes that we think control infection by a parasitic nematode. Looking at our pilot data we see that these sets of genes differ a lot among different individual worms and we think this is a tell-tale sign that the worms are using these sets of genes to compete with one another inside the host, and that this competition is driving the harm that these parasites cause to their hosts.We are now proposing to investigate these sets of genes is more detail, to very precisely understand how they differ among individual worms, and to see whether or not different genetic types naturally occur together inside a host. By looking at the gene sequences we'll also predict which worms should be most different from each other in how they infect hosts, and then we'll test this in experiments with laboratory animals. In this way our work will move from just comparing gene sequences to also testing how nematode worms actually infect hosts. We will study this in a nematode parasite called Strongyloides that naturally infects rats in the UK, but which we can also study in the lab.By testing our ides we will establish whether or not we have discovered the sets of genes that parasitic nematodes use to infect hosts. If so, this opens up a whole new understanding of how nematode worms infect and cause harm to their hosts, which can then be used to better understand, predict and treat these infections in the future.