The structure and function of nematode pathogenicity islands

线虫致病岛的结构与功能

• 批准号: BB/X008673/1
• 负责人: Mark Viney
• 金额: $ 78.67万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX008673%2F1
• 关键词: structure; function; nematode; pathogenicity; islands

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.

寄生蠕虫是地球上最丰富的寄生虫之一-动物和植物感染它们是正常的。蠕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且重要，但我们不了解它们如何伤害宿主。具体来说，我们不知道它们使用什么基因来生活在宿主体内并以宿主为食，但这最终会伤害宿主。如果我们对这些基因有更多的了解，我们就能更好地预测它们是如何进化的，我们就能想出更好地控制这些寄生虫的新方法，我们需要这样做来保护人类和动物的健康，并确保粮食生产。我们已经发现了12组集中的基因，我们认为它们可以控制寄生线虫的感染。从我们的试验数据来看，这些基因组在不同的蠕虫个体之间有很大的差异，我们认为这是一个信号，表明蠕虫正在使用这些基因组在宿主体内相互竞争，这种竞争正在推动这些寄生虫对宿主造成的伤害。我们现在建议更详细地研究这些基因组，以非常精确地了解它们在个体蠕虫之间的差异，并观察不同的基因类型是否会在宿主体内自然地一起出现。通过观察基因序列，我们还可以预测哪种蠕虫在感染宿主的方式上彼此最不相同，然后我们将在实验室动物身上测试这一点。通过这种方式，我们的工作将从仅仅比较基因序列转移到测试蠕虫如何感染宿主。我们将在一种名为类圆线虫的线虫寄生虫中研究这一点，这种寄生虫在英国自然感染大鼠，但我们也可以在实验室中研究。通过测试我们的ides，我们将确定我们是否已经发现了寄生线虫用来感染宿主的基因组。如果是这样的话，这就为蠕虫如何感染并对其宿主造成伤害开辟了一个全新的理解，然后可以用来更好地理解，预测和治疗这些感染。