Phylogenetic modelling of host-pathogen co-evolution

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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).