Approaches to detect and block transition stages in Trypanosoma brucei

检测和阻断布氏锥虫过渡阶段的方法

• 批准号: 2447179
• 金额: --
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2447179
• 关键词: Approaches; detect; block; transition; stages

Studentship strategic priority area:Quantitative Systems Medicine Keywords:Single cell; Trypanosoma brucei; Trajectory inference; cell progression Trypanosomatids are a grouping of single-celled parasites belonging to the order Kinetoplastea. One of these parasites, Trypanosoma brucei, is responsible for the sleeping sickness diseases transmitted by the tsetse fly, affecting humans and livestock in Africa. Only a handful of drugs are available, many of which are not efficient and have severe side effects.Emerging data has explored the factors needed for some, but by no means all, aspects of transmission between the distinct parasites forms found as the parasite moves from mammals to vector and back. Notably, the developmental programme in the tsetse vector is poorly understood and, crucially, little work has examined the temporal order of gene expression changes during life cycle transitions. In this PhD we aim to detect genes essential in the transition from the vector stages to the mammalian stages in T. brucei in order to identify pathways that could be targeted by novel compounds. We will obtain and analyse single cell RNA-seq from these stages. Through pseudo time and branching analysis we will detect genes crucial for transition. Finally, the student will ablate these genes and attempt to block the factors, to ask how they act in the life cycle and test if they might be drug targets. This is an interdisciplinary project to train students in quantitative methods and brings together a supervisor team with a diverse background. By the end of the PhD, the student will have learned novel genomics and laboratory techniques that are crucial in the field of precision medicine.

学生奖学金战略优先领域：定量系统医学关键词：单细胞；布氏锥虫；轨迹推断；细胞进展 锥虫是一组属于动质体目的单细胞寄生虫。其中一种寄生虫是布氏锥虫，它是由采采蝇传播的昏睡病的罪魁祸首，影响了非洲的人类和牲畜。可用的药物只有少数，其中许多药物效率不高，而且有严重的副作用。新出现的数据探索了寄生虫在哺乳动物与媒介之间来回传播过程中发现的不同寄生虫形式之间传播的某些（但绝不是全部）方面所需的因素。值得注意的是，人们对采采蝇载体的发育程序知之甚少，而且最重要的是，很少有人研究生命周期转变期间基因表达变化的时间顺序。在这个博士学位中，我们的目标是检测布氏锥虫从载体阶段向哺乳动物阶段转变所必需的基因，以便确定新化合物可以靶向的途径。我们将从这些阶段获取并分析单细胞 RNA-seq。通过伪时间和分支分析，我们将检测对转变至关重要的基因。最后，学生将消融这些基因并尝试阻断这些因素，询问它们在生命周期中的作用并测试它们是否可能是药物靶标。这是一个跨学科项目，旨在培训学生定量方法，并汇集了一支具有不同背景的导师团队。在博士学位结束时，学生将学习在精准医学领域至关重要的新型基因组学和实验室技术。