Title: "Genome-led vaccine target discovery for animal African trypanosomiasis”
Speaker: Gavin Wright, PhD
Senior Group Leader
Cell Surface Signalling Laboratory
Wellcome Sanger Institute
Hinxton, Cambridgeshire, UK
Abstract: The livelihoods of millions of people living in Africa are at risk due to infectious diseases that affect the health of livestock animals that provide them with essential food, milk, clothing and draught power. One major livestock disease is animal African trypanosomiasis (AAT) which is caused by blood-dwelling Trypanosome parasites that affect many important farm animals including cattle, goats, sheep, horses, and pigs. AAT is endemic from the Southern edge of the Sahara to Zimbabwe/Mozambique and is estimated to cause 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 mainly caused by two species of Trypanosome: T. congolense and T. vivax which are primarily transmitted through the bite of an infected tsetse fly. The few drugs for AAT are not satisfactory: they cause serious side effects, and parasite resistance to these drugs is increasing. Importantly, even if new effective drugs were developed, these Trypanosome parasites are endemic in wild animals meaning there would be little chance of eradicating the disease, and so livestock animals would require constant monitoring and treatment. The best solution would be the deployment of an effective vaccine; however, vaccinating against trypanosome infections has long been considered unachievable because the surface of these parasites is immunologically protected by a highly abundant protein that is constantly changing within the population.
Using the genome sequence to identify non-variant parasite cell surface proteins, we have produced a library of parasite proteins and systematically tested their candidature as vaccine candidates using a murine infection model. Our results indicate that it is possible to identify non-variant parasite protein that can elicit protective immune responses, suggesting that a vaccine to treat AAT may be achievable.
Bio: Gavin is interested in the molecular basis of cellular recognition events. The goals of his research are to obtain a mechanistic understanding of how cells interact both within our own bodies and with pathogens. Ultimately, this knowledge will inform the rational design of intervention strategies for the treatment and prevention of genetic and infectious diseases.
Gavin graduated from the University of Oxford with a degree in Biochemistry in 1996 before studying for a D.Phil. within the Medical Research Council (MRC) Cellular Immunology Unit with Professor Neil Barclay at the Sir William Dunn School of Pathology.
He initially worked on CD200 (formally OX2), a cell surface protein expressed in both the immune and nervous systems and discovered its receptor, which was found to be restricted to myeloid-lineage cells. Together with collaborators, Gavin’s team showed that endogenous CD200 and also close homologues of this protein which had been captured by both pox and herpes viruses delivered restrictive signals to macrophages to locally suppress their activation. It is these studies that sparked his broad interests in cell surface receptor proteins and their role in cellular signalling and recognition processes. For his postdoc, Gavin worked with Dr Julian Lewis at Cancer Research UK, London where he studied the Notch signalling pathway, using the zebrafish model organism.
His research at the Wellcome Sanger Institute has focused on taking large-scale systematic approaches to identify novel receptor-ligand pairs that initiate intercellular signalling. In particular, Gavin is interested in the low affinity interactions that are a common feature of cell surface receptor interactions and develops new methods to identify this type of binding event which cannot be easily detected using other scalable techniques. The laboratory has identified many novel receptor-ligand pairs including Juno-Izumo, which is essential for mammalian sperm-egg recognition, and RH5-basigin that is required for the invasion of blood cells by the malaria parasite.
Date: Monday, November 1, 2021
Time: 12-1 pm
Location: Hill Pavilion, Room 132
University of Pennsylvania School of Veterinary Medicine
380 S University Ave, Philadelphia, PA 19104
You can also attend virtually. Virtual Link: Zoom
Questions? Please contact Sue Waddington-Pilder if you have questions (firstname.lastname@example.org).