Organisation and regulation of parasitism-associated genomic islands

据估计，至少有40%的动物有寄生的生活方式。寄生虫造成了巨大的全球疾病负担，例如，土壤传播的蠕虫，如圆线虫寄生虫，感染了全球15亿人。研究寄生虫的基因组和遗传基础对于理解寄生虫成为寄生虫的基本原理和寄生虫的进化很重要。此外，了解涉及寄生虫的基因是如何调节和组织的，可以为开发寄生虫感染的控制策略和治疗方法提供信息。我们发现，对寄生起重要作用的基因在物理上排列在基因组中的簇或“寄生相关基因组岛”(PGI)中。将这些基因组织到pGI中可能对在感染过程中迅速启动这些基因很重要。这对寄生虫来说很重要，这样它才能对宿主的恶劣环境做出快速反应并在其中生存。在这个项目中，我们将研究一种感染哺乳动物肠道的寄生虫中的PGI。本研究旨在研究几种近缘关系较近的肠道寄生虫(Strongyloids spp.)以识别PGI中共享或不同的功能。我们将使用DNA和RNA测序来产生数据来实现这一目标。我们还将开展实验，探索如何监管PGI。我们将寻找与组蛋白蛋白相关的特定信号，组蛋白蛋白参与包装DNA序列，以确定PGI在寄生过程中是否受到组蛋白蛋白的精确调控。我们还将使用一种名为Hi-C的技术来了解在寄生过程中基因组的不同部分是如何相互作用的，以及这些相互作用是如何与PGI相关的。最后，我们发现，不编码蛋白质的RNA分子也位于PGI中，这些分子已知对调节邻近的基因很重要。我们将使用一种改进的方法对这些非编码RNA分子进行测序和鉴定，并调查它们是否参与打开或关闭PGI中的基因。

It is estimated that at least 40% of animals have a parasitic lifestyle. Parasites contribute to a huge global disease burden, for example, soil-transmitted helminths such as Strongyloides parasites, infect 1.5 billion people globally. Investigating the genomic and genetic basis of parasitism is important for understanding the fundamental principles of what makes a parasite a parasite and the evolution of parasitism. Furthermore, understanding how the genes involved in parasitism are regulated and organised can inform the development of control strategies and treatments for parasite infections. We have discovered that genes important for parasitism are physically arranged in clusters or 'parasitism-associated genomic islands' (PGIs) in the genome. Organisation of these genes into PGIs is likely to be important in rapidly turning on these genes during infection. This is important for the parasite so that it can rapidly respond to, and survive in, the harsh environment of its host. In this project we will investigate PGIs in a parasitic worm which infects the gut of mammals. We aim to investigate the common features and differences of PGIs across several different species of closely related gut worm parasites (Strongyloides spp.) to identify features in PGIs that are shared or different. We will use DNA and RNA sequencing to generate data to carry out this aim. We will also carry out experiments to explore how PGIs are regulated. We will look for specific signatures associated with histone proteins, which are involved in packaging DNA sequences, to establish if PGIs are precisely regulated by histone proteins during parasitism. We will also use a technology called Hi-C to see how different parts of the genome interact with each other during parasitism and how these interactions relate to PGIs. Finally, we have discovered that RNA molecules that don't code for proteins are also located in PGIs and these molecules are known to be important for regulating genes that are in close proximity. We will use an improved method to sequence and identify these non-coding RNA molecules, and investigate if they are involved in turning the genes on or off in PGIs.