DNA recombination pathways and antigenic variation in Trypanosoma brucei

非洲锥虫是哺乳动物的单细胞寄生虫，在撒哈拉以南非洲具有重要的医学、兽医和经济意义。它们已经被研究了100多年，揭示了生物学的许多新方面，揭示了包括人类在内的所有生物的基本过程。锥虫逃脱了被哺乳动物杀死？使用一种称为抗原性变异的策略。抗原变异的一个主要组成部分是寄生虫内特定基因的重排。S基因组通过一种称为重组的反应。所有生物体都使用重组来修复其基因组的损伤，因此需要保持信息来源的完整性，这决定了生物体的各个方面。S生长、发育和繁殖。我们已经证明锥虫利用这种修复途径来进行抗原变异。然而，我们对重组如何在抗原变异中起作用的理解尚不清楚，它对锥虫基因组和生物学的其他特征的贡献方式也不清楚。该项目将研究导致锥虫重组和抗原变异的因素，包括它们如何相互作用，并将描述一种以前未在这种寄生虫中描述过的新型重组形式。解决这些问题将对我们理解所有生物体中的重组具有根本性的意义，但也可能揭示锥虫对这一过程的特定适应，这些适应可能在未来用于临床应用。

African trypanosomes are single cell parasites of mammals that have major medical, veterinary and economic importance in sub-Saharan Africa. They have been studied for over 100 years, and have revealed many novel aspects of biology that have shed light on fundamental processes in all organisms, including humans. Trypanosomes escape being killed by the mammal?s immune system using a strategy termed antigenic variation. A major component of antigenic variation is rearrangements of specific genes within the parasite?s genome through a reaction termed recombination. Recombination is used in all organisms to repair damage to their genome, and is therefore needed to maintain the integrity of this information source, which dictates all aspects of an organism?s growth, development and reproduction. We have shown that trypanosomes have harnessed this repair pathway for antigenic variation. Nevertheless, our understanding of how recombination acts in antigenic variation is unclear, as is the way that it contributes to other features of the genome and biology of trypanosomes. This project will examine the factors that contribute to trypanosome recombination and antigenic variation, including how they interact, and will characterise a novel form of recombination not previously described in this parasite. Addressing these questions will have fundamental implications for our understanding of recombination in all organisms, but may also reveal specific adaptations of this process in trypanosomes that may be exploited in the future for clinical applications.