Establishing the roles of Plasmodium falciparum merozoite invasion proteins
- Research Opportunity
- Number of Honour Places Available
- Medicine and Radiology
- Burnet Institute
|Dr Paul Gilsonfirstname.lastname@example.org||0433685205|
|A. Prof. Freya Fowkesemail@example.com|
Summary This project aims to follow 4 different proteins involved in malaria parasite invasion of red blood cells to resolve their order of action and to understand their invasion functions.
About 40% of the world’s population, mostly children and pregnant women, are at risk of malaria. Malaria vaccines offer the hope of long-term disease control and elimination, but thus far highly effective vaccines have not been developed despite much effort. The most effective RTS,S vaccine produced to date halves the occurrence of severe disease for about 1 year in young children by targeting the sporozoite parasite form that enters the body during mosquito bite. There is a need to find additional vaccine antigens that block the downstream parasite forms that produce large-scale infection of the blood which causes symptomatic malaria disease. Merozoites are extracellular parasite forms that invade erythrocytes where the parasites grow and produce more merozoites. Merozoite surface proteins support erythrocyte entry and are considered ideal vaccines since antibodies that block these proteins could directly inhibit invasion or recruit immune factors to destroy the merozoites. This project aims to follow 4 different proteins involved in merozoite invasion and resolve their order of action to understand their invasion functions. This will be achieved by tagging the genes for invasion proteins with tags for green fluorescence protein (GFP) and the glmSriboswitch using the CRISPR/Cas9 system. GFP will permit the location of these proteins to be visualised during live invasion microscopy imaging that will help define the proteins’ roles. The riboswitch will enable expression of the invasion proteins be switched off so the effects of protein loss on invasion can be studied. Laboratory techniques will include parasite culture, plasmid cloning, parasite transfections and live microscopy. A greater understanding of when merozoite proteins are deployed on the parasite cell’s surface and improved knowledge of their biological function could help prioritise which proteins should be developed into future vaccines.
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