Essential role of glycobiology in malaria parasites

Essential role of glycobiology in malaria parasites

Project details

Malaria causes approximately 600,000 deaths annually and remains an enormous global health problem. One reason for this is that there is no highly effective vaccine. The only licensed malaria vaccine RTS,S (Mosquirix) offers poor efficacy that wanes over time. Part of the problem may be that the recombinant malaria antigen in RTS,S is not glycosylated like the endogenous malaria protein.  Glycosylation is important for vaccine development because carbohydrates decorate the surface of nearly all microbes and carbohydrate antigens activate immune cells and are recognised by antibodies.

It has long been believed that malaria parasites do not glycosylate proteins. On the contrary, these parasites do glycosylate proteins and we have shown this is involved in infecting the mosquito and human host. This is significant because several malaria vaccines in development are aimed at preventing infection by using antigens that are glycosylated by malaria parasites but not in the vaccine.

This project focuses on understanding the role of glycosylation in malaria parasite infection of mosquitoes and the liver, before a malaria infection can take hold. It will also determine the function of uncharacterised glycosylated proteins as potential vaccine candidates.

The project will use state-of-the-art conditional genetic systems to identify essential components of the glycosylation machinery and substrates in Plasmodium falciparum transmission. The project will involve working in an insectary with mosquitoes, producing all lifecycle stages and studying infection biology in multiple hosts. The student will learn a multidisciplinary skill set including parasitology, molecular genetics, cell culture, preclinical infection models, microscopy, proteomics and biochemical techniques.

 

About our research group

Our research is aimed at understanding how Plasmodium falciparum, the causative agent of the most severe form of malaria, infects humans and mosquitoes to cause disease. To establish infection in the human and mosquito hosts, malaria parasites must be motile within tissues in order to penetrate deeper and identify and invade different host cells. The ability to achieve this relies on a subset of virulence proteins that are glycosylated. A deeper understanding of the role of glycosylation is important for the development of a vaccine and new treatments required to treat and control this disease.

Our laboratories are interested in the identification and development of small molecules with antimalarial activity, which are used to discover and interrogate biological mechanisms essential to the malaria parasite. The project may identify new targets for small molecule screening and development.

 

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