DNA recombination pathways and antigenic variation in Trypanosoma brucei

布氏锥虫的 DNA 重组途径和抗原变异

• 批准号: G0401553/1
• 负责人: Richard McCulloch
• 金额: $ 47.15万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0401553%2F1
• 关键词: DNA; recombination; pathways; antigenic; variation

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.

非洲锥虫是哺乳动物的单细胞寄生虫，在撒哈拉以南非洲地区具有重大的医学、兽医和经济重要性。人们对其进行了 100 多年的研究，揭示了生物学的许多新颖方面，这些方面揭示了包括人类在内的所有生物体的基本过程。锥虫使用一种称为抗原变异的策略逃脱了哺乳动物免疫系统的杀死。抗原变异的一个主要组成部分是通过称为重组的反应对寄生虫基因组内的特定基因进行重排。所有生物体都使用重组来修复其基因组的损伤，因此需要维持该信息源的完整性，该信息源决定生物体生长、发育和繁殖的各个方面。我们已经证明锥虫已经利用这种修复途径来实现抗原变异。然而，我们对重组如何在抗原变异中发挥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是如此。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，并将表征一种以前未在该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产生根本性影响，但也可能揭示锥虫中这一过程的具体适应，这些适应将来可能用于临床应用。