Phylogenetic modelling of host-pathogen co-evolution

宿主-病原体共同进化的系统发育模型

• 批准号: 2105528
• 金额: --
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2105528
• 关键词: Phylogenetic; modelling; host; pathogen; co

African animal trypanosomiasis (AAT) is a lethal livestock disease caused by multiple Trypanosoma species, endemic in 37 sub-Saharan countries. Resolving AAT is an enormous challenge because trypanocidal drugs frequently solicit parasite resistance, while vaccines are unavailable because the trypanosome surface is cloaked by a variable surface glycoprotein (VSG) coat. Serial replacement of the active VSG through antigenic variation allows the parasite to evade host immunity indefinitely. Antigenic variation is the common thread linking the physiology, epidemiology and evolution of AAT, and key to understanding and preventing animal disease. Our previous work showed that trypanosome species differ in their inherent antigenic diversity due to differences in recombination rate. While others have tried to model the interaction between trypanosome and host immunity in the past to explain antigenic diversity, no-one has provided a robust mathematical model of VSG molecular evolution, and therefore the mechanisms for generating antigenic diversity. The project aim is to develop mathematical models that can explain how VSG sequence diversity is generated in different trypanosome species during natural and experimental infections. Our approach is interdisciplinary, combining transcriptomic analysis of trypanosome infections (Liverpool) with mathematical modelling of sequence evolution (Newcastle).

非洲动物锥虫病（AAT）是由多种锥虫属物种引起的致命牲畜疾病，在37个撒哈拉以南国家流行。解决AAT是一个巨大的挑战，因为杀锥虫药物经常引起寄生虫抗性，而疫苗是不可用的，因为锥虫表面被可变表面糖蛋白（VSG）外壳所掩盖。通过抗原变异连续替换活性VSG，使寄生虫无限期地逃避宿主免疫。抗原变异是联系AAT的生理学、流行病学和进化的共同线索，也是理解和预防动物疾病的关键。 我们以前的工作表明，锥虫物种不同，由于重组率的差异，其固有的抗原多样性。虽然其他人试图在过去建立锥虫和宿主免疫之间的相互作用的模型来解释抗原多样性，但没有人提供VSG分子进化的可靠数学模型，因此没有人提供产生抗原多样性的机制。 该项目的目的是开发数学模型，可以解释VSG序列多样性是如何在自然和实验感染过程中在不同的锥虫物种中产生的。我们的方法是跨学科的，将锥虫感染的转录组学分析（利物浦）与序列进化的数学建模（纽卡斯尔）相结合。