High-throughput decoding of mitosis in trypanosome parasites

正确的细胞分裂对生命至关重要。然而，实现这一目标的方式在不同的有机体之间存在很大差异。对于许多重要的寄生虫物种来说尤其如此，它们的分裂往往与宿主细胞非常不同。了解这种细胞分裂机制对于了解寄生虫的基本生物学很重要，但也因为寄生虫和宿主之间的差异为开发新的治疗方法提供了机会。非洲锥虫是血液中的单细胞寄生虫。它们在撒哈拉以南非洲造成一种致命的人类疾病和一种牛的消耗性疾病，每年导致约300万头牛死亡，并给非洲经济造成约40亿美元的损失。非洲锥虫具有一种与其病理相关的不寻常的基因组结构，包括约120条染色体，所有这些染色体都由一种与大多数其他真核生物非常不同的细胞分裂机制移动。这个系统是如何工作的是寄生虫学中一个重要的悬而未决的问题，它将告诉我们这个系统是如何进化的，以及哪些部分是潜在的药物靶点。该实验室已经开发出一种基因组方法，允许研究人员产生并跟踪10万个突变，以评估基因在特定过程中的功能。这个博士项目将使用这项新技术，以及生化和细胞生物学方法来了解非洲锥虫和相关寄生虫的细胞分裂机制。通过将全基因组方法与特定突变相结合，我们将定义染色体分离机制的基本部分，识别新的组件，并破译系统是如何组合在一起的。

Correct cell division is essential to life. The way in which this is achieved, however, differs greatly between organisms. This is particularly the case for many important parasite species, the division of which are often very different from host cells. Understanding this cell division machinery is important to understanding the basic biology of the parasite, but also because differences between parasite and host present opportunities for the development of new treatments. African trypanosomes are single-celled parasites of the blood. They cause a deadly disease in humans in sub-Saharan Africa and a wasting disease of cattle that kills ~3 million cattle per year and creates an estimated loss of ~$4 billion from African economies. African trypanosomes have an unusual genome structure that is linked to their pathology and encompasses ~120 chromosomes all of which are moved by a cell division machinery that is very different from most other eukaryotes. How this system works is an important outstanding question in parasitology and will tell us how the system evolved as well as which parts are potential drug targets. The lab has developed a genomic method that allows researchers to generate and follow 100,000s of mutants to assess the function of genes in a specific process. This PhD project will use this new technology, along with biochemical and cell biological approaches to understand the cell division machinery of African trypanosomes and related parasites. By combining the genome-wide approach with specific mutants, we will define the essential parts of the chromosome segregation machinery, identify new components and decode how the system is put together.