Phylogenetic modelling of host-pathogen co-evolution

非洲动物锥虫病(AAT)是由多种锥虫引起的一种致命性家畜疾病，在撒哈拉以南37个国家流行。解决AAT是一个巨大的挑战，因为杀锥虫的药物经常会引起寄生虫耐药性，而疫苗则因为锥虫表面被可变表面糖蛋白(VSG)覆盖而得不到。通过抗原变异对活性VSG进行连续替换，可以使寄生虫无限期地逃避宿主的免疫。抗原变异是联系AAT生理、流行病学和进化的共同线索，是认识和预防动物疾病的关键。我们以前的工作表明，由于重组率的不同，锥虫物种的固有抗原多样性也不同。虽然过去有人试图通过模拟锥虫和宿主免疫之间的相互作用来解释抗原多样性，但还没有人提供一个强有力的数学模型来解释VSG分子进化，从而解释产生抗原多样性的机制。该项目的目的是开发数学模型，解释不同锥虫物种在自然感染和实验感染期间如何产生VSG序列多样性。我们的方法是跨学科的，结合了锥虫感染的转录分析(利物浦)和序列进化的数学模型(纽卡斯尔)。

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).