The relevance of transposable element dynamics for host parasite interactions

转座因子是一种移动的遗传因子，在真核生物基因组中占有很大比例。TE调节对于维持基因组稳定性是重要的，并且部分由小RNA进行。我们最近发现TE活性与寄生直接相关的证据，因为：（i）寄生虫转座酶（参与将DNA TE插入基因组的酶）的表达在感染期间增加;（ii）特定的小干扰RNA（siRNA）在感染期间调节寄生虫中TE的活性。了解寄生虫的遗传基础和后果为改进寄生虫的治疗和控制提供了机会。本项目旨在研究类圆线虫及其宿主环境中的TE在寄生中的作用。类圆线虫的生命周期有两个遗传上相同的阶段：一个是寄生的，感染人类和其他动物的肠道，一个是自由生活，不造成伤害。我们将在自由生活的“控制”和寄生阶段之间进行直接比较，以了解寄生期间TE活动如何变化以及TE如何调节。该项目的结果将有助于我们在TE生物学和寄生虫学的重要和新兴领域的知识。该项目解决了三个关键问题：1。寄生虫转座酶活性增加与宿主免疫反应有关吗？RNAseq将用于鉴定寄生虫在不同宿主条件下的TE表达变化，例如不存在Th 2（抗炎、抗线虫）或Th 1（炎症）免疫应答，以建立寄生虫对宿主环境的TE应答。2.在感染过程中，寄生虫的TE-sRNA活性如何变化？我们将量化整个感染过程中TE的表达水平，并监测TE和调节它们的siRNA是否在感染的早期、高峰和晚期差异表达。我们将使用RNAi靶向siRNA途径中涉及的基因来阻断TE调控途径。3.感染期间宿主TE活性是否发生变化？我们将在感染期间和感染后对宿主（大鼠）组织（例如肠）进行RNAseq，以确定TE活性是否参与宿主对寄生虫的反应。申请人应具有强大的第一学位或硕士学位，对实验室和生物信息学工作感兴趣。成功的申请人将在亨特实验室（巴斯）工作，并将与海沃德（埃克塞特，彭林校区），普罗塔西奥（剑桥）和赫斯特（巴斯）实验室的共同主管密切合作。学生将接受寄生虫学和RNA生物学实验室技术的培训，以及包括转录组学和TE注释在内的生物信息学技能。

Transposable elements (TEs) are mobile genetic elements that comprise a large proportion of eukaryotic genomes. TE regulation is important for maintaining genomic stability and is in part carried out by small RNAs. We recently found evidence that TE activity is directly linked to parasitism because: (i) Expression of parasite transposases (enzyme involved in insertion of DNA TEs into the genome) increases during infection; (ii) Specific small-interfering RNAs (siRNAs) regulate the activity of TEs in the parasite during infection. Understanding the genetic basis and consequences of parasitism offers opportunities for improved treatment and control of parasites. This project aims to investigate the role of TEs in parasitism in the parasitic nematode Strongyloides and its host environment. The Strongyloides lifecycle has two genetically identical stages: one is parasitic and infects the intestine of humans and other animals, one is free-living causing no harm. We will make direct comparisons between the free-living 'control' and parasitic stages to understand how TE activity changes during parasitism and how TEs are regulated. The results from this project will contribute to our knowledge in the important and emerging field of TE biology and parasitism. The project addresses three key questions: 1. Is increased parasite transposase activity related to the host immune responses? RNAseq will be used to identify TE expression changes in the parasite under different host conditions e.g. absence of either a Th2 (anti-inflammatory, anti-nematode) or Th1 (inflammatory) immune response, to establish parasite TE responses to the host environment. 2. How does TE-sRNA activity in the parasite change during infection? We will quantify TE expression levels throughout infection and monitor if TEs, and the siRNAs that regulate them, are differentially expressed at early, peak and late stages of infection. We will use RNAi to target genes involved in siRNA pathways to characterise TE regulation pathways. 3. Does host TE activity change during infection? We will perform RNAseq on host (rat) tissues e.g. intestine, during and post-infection, to ascertain if TE activity is involved in the host response to parasitism. Applicants should have a strong first degree or masters with an interest in laboratory-based and bioinformatic work. The successful applicant will be based in the Hunt lab (Bath) and will work closely with co-supervisors in the Hayward (Exeter, Penryn Campus), Protasio (Cambridge) and Hurst (Bath) labs. The student will receive training in laboratory-based techniques in parasitology and RNA biology, and bioinformatics skills including transcriptomics and TE annotation.