The relevance of transposable element dynamics for host parasite interactions

转座元件动力学与宿主寄生虫相互作用的相关性

• 批准号: 2605148
• 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: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2605148
• 关键词: relevance; transposable; element; dynamics; host

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.

转座元件（TE）是构成真核基因组大部分的可移动遗传元件。 TE 调节对于维持基因组稳定性很重要，并且部分由小 RNA 执行。我们最近发现证据表明 TE 活性与寄生直接相关，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。了解寄生的遗传基础和后果为改善寄生虫的治疗和控制提供了机会。本项目旨在研究TEs在寄生线虫类圆线虫及其寄主环境中的寄生作用。类圆线虫的生命周期有两个基因相同的阶段：一是寄生并感染人类和其他动物的肠道，一是自由生活，不会造成伤害。我们将直接比较自由生活的“控制”阶段和寄生阶段，以了解寄生期间 TE 活性如何变化以及 TE 是如何受到调节的。该项目的结果将有助于我们在 TE 生物学和寄生学这一重要且新兴领域的知识。该项目解决了三个关键问题： 1. 寄生虫转座酶活性的增加是否与宿主免疫反应有关？ RNAseq 将用于识别不同宿主条件下寄生虫的 TE 表达变化，例如缺乏 Th2（抗炎、抗线虫）或 Th1（炎症）免疫反应，以建立寄生虫对宿主环境的 TE 反应。 2. 寄生虫感染期间TE-sRNA活性如何变化？我们将量化整个感染过程中的 TE 表达水平，并监测 TE 以及调节它们的 siRNA 在感染的早期、高峰和晚期阶段是否存在差异表达。我们将使用 RNAi 来靶向 siRNA 通路中涉及的基因，以表征 TE 调控通路。 3.感染过程中宿主TE活性是否发生变化？我们将对宿主（大鼠）组织进行 RNAseq，例如大鼠组织。感染期间和感染后肠道，以确定 TE 活性是否参与宿主对寄生的反应。申请人应拥有良好的学士学位或硕士学位，并对实验室和生物信息工作感兴趣。成功的申请者将在亨特实验室（巴斯）工作，并将与海沃德（埃克塞特，彭林校区）、Protasio（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 生物学实验室技术以及转录组学和 TE 注释等生物信息学技能的培训。