The focus of our research is understanding how to generate effective immunity against the malaria parasite Plasmodium. Malaria kills from 500,000 to 1 million people each year. A game-changer in the fight against malaria would be an effective vaccine. We know that two of the most effective branches of the immune system capable of fighting malaria are antibodies (which are made by B cells) and CD8+ T cells. Antibodies can block parasites in the blood as they travel from the site of the infectious mosquito bite to the liver, where infection is first established. CD8+ T cells are specialized killers that can patrol the liver, and find and eliminate the Plasmodium infected cells. If we can understand how to harness these responses properly, we might be able to develop vaccines capable of giving robust and durable protection against malaria.
Accordingly, research in my group is focused on the 2 broad areas of B cell responses to malaria and T cell responses to malaria. We have opportunities for honours and post-graduate projects in both these areas.
B cell responses to malaria
Specific antibodies can bind to the malaria parasites injected by the mosquitoes (called sporozoites) and prevent them from establishing infection in the liver. However we do not know how to generate antibody responses that are strong enough and sustained enough for true protective immunity. We are using novel tools to track the B cells that mediate the antibody response to try and determine how to achieve this aim. In collaboration with Colin Jackson in the Research School of Chemistry we have also been examining the structures of sporozoite-neutralizing antibodies to determine how these antibodies work.
T cell responses to malaria
CD8+ T cells are specialized cells that specifically recognize cells infected with pathogens or tumour cells. Using intra-vital imaging we are unraveling how CD8+ T cells patrol the sinusoids and find malaria parasites. Because the actual number of cells in the liver that are infected in very small this is like finding a needle in a haystack. We are trying to determine the critical molecules involved in this patrolling behavior as well as the ways that CD8+ T cells actually kill parasites. Based on these molecules we can define different subpopulations of CD8+ T cells in the liver and work out which of these are likely to be best able to protect.