WR DTP project: Structural architecture of vaccine targets for the parasitic livestock disease animal African trypanosomiasis

The livelihoods of millions of people living in Africa are at risk due to infectious diseases that affect the health of livestock animals that they depend on for essential food, milk, clothing and draught power. One major livestock disease is animal African trypanosomiasis (AAT) which causes annual productivity losses of over $1 billion, representing a major barrier for the socioeconomic advancement of many African countries. Such is the impact of this disease that the United Nations Food and Agricultural Organisation consider it to “lie at the heart of Africa’s struggle against poverty”.

The disease is caused by unicellular blood-dwelling parasites called trypanosomes which are transmitted by the bite of infected tsetse flies and are responsible for sleeping sickness in humans. We have recently made a major advance by identifying vaccine candidates for both species of trypanosome responsible for AAT: Trypanosoma vivax and Trypanosoma congolense. Excitingly, both vaccine targets are cell surface proteins that are localized to the parasite flagellum suggesting common vulnerabilities that can be exploited. We would now like to understand why targeting these proteins with vaccine-elicited antibodies leads to parasite killing to improve vaccine efficacy.

The project will involve expressing the parasite vaccine targets using recombinant protein technologies and determining their structure using X-ray crystallography and/or cryogenic electron microscopy in complex with protective antibodies and other parasite proteins they interact with. The structures will be used to improve vaccine design which will be tested in animal models and also reveal fundamental aspects of the biology of these clinically and economically important parasites. Finally, because the regulatory frameworks for livestock vaccines are understandably less stringent than for humans, our aim is to provide a timely solution to an important problem that will improve the lives of people living in low and middle income countries.

The White Rose DTP in Mechanistic Biology is committed to recruiting extraordinary future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.