The role of 'parasitism islands' in infection by soil-transmitted helminths

“寄生岛”在土源性蠕虫感染中的作用

• 批准号: 2749586
• 金额: --
• 依托单位: University of Bath
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2749586
• 关键词: role; parasitism; islands; infection; soil

Understanding the mechanisms soil-transmitted helminth parasites (STHs) have evolved to infect their host is an important step towards developing much needed improvements in treatments and control methods. It has recently been discovered that parasitism-associated genes in STHs (e.g. genes coding for proteins that manipulate the host immune response) are physically clustered in the genome into 'parasitism islands'. These regions share many similarities with the pathogenicity islands that are well characterised in bacteria, and we hypothesise that parasitism islands have a fundamentally important role in parasite infection. Parasitism islands offer potential targets for anthelminthic drugs and alternative treatment strategies. Using a combination of lab-based and bioinformatic approaches we will investigate the role and organisation of parasitism islands, focusing on the questions: Are parasitism islands characteristic of parasite genomes in general? How is gene expression regulated in parasitism islands? and what is the functional role of parasitism islands in parasite-host interaction?For the lab-based components, the model Strongyloides ratti will be used. It is a well-established lab model for parasite infection and a close relative of the human parasite S. stercoralis which infects 600 million people worldwide. The Strongyloides parasites are one of the few parasitic nematodes that CRISPR/Cas9 techniques have been established for and we will use these methods to investigate the functional role of genes in parasitism islands. We will also perform functional analysis of epigenetic marks, including investigating the role of histone modifications and small RNAs in the regulation of virulence hotspots at different stages of infection. Based on our findings with S. ratti we may then go on to carry out these methods on other helminth species. Together these approaches will help us to better understand the genetic toolbox used by parasites to successfully infect the host.

了解土壤传播蠕虫寄生虫（STH）感染宿主的机制是发展急需的治疗和控制方法的重要一步。最近发现STH中的寄生虫相关基因（例如编码操纵宿主免疫反应的蛋白质的基因）在基因组中物理聚集成“寄生虫岛”。这些地区有许多相似之处的致病性岛屿，以及在细菌中的特点，我们假设，寄生虫岛有一个根本性的重要作用，寄生虫感染。寄生虫岛为驱虫药物和替代治疗策略提供了潜在的目标。使用基于实验室和生物信息学的方法相结合，我们将调查的作用和组织的寄生岛，专注于问题：寄生岛的特点一般寄生虫基因组？寄生岛中基因表达是如何调控的？寄生岛在寄生物-宿主相互作用中的功能作用是什么？对于基于实验室的组件，将使用模型圆线虫。它是一个完善的寄生虫感染的实验室模型，也是人类寄生虫S的近亲。感染全球六亿人的粪蝇类圆线虫寄生虫是已经建立CRISPR/Cas9技术的少数寄生线虫之一，我们将使用这些方法来研究基因在寄生岛中的功能作用。我们还将进行表观遗传标记的功能分析，包括研究组蛋白修饰和小RNA在感染不同阶段毒力热点调控中的作用。根据我们对S.然后我们可以继续对其他蠕虫物种进行这些方法。这些方法将有助于我们更好地了解寄生虫成功感染宿主所使用的遗传工具箱。