Refolding of exported proteins in malaria parasites
- 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 In this project we aim to trap exported reporter proteins in the process of being exported in malaria parasites while protein refolding factors are at work attempting to refold their client proteins. These refolding proteins will then be captured and identified so their functions can be investigated by reverse genetic and chemical approaches.
Malaria is still one of the world’s most important infectious diseases. Despite a halving in the impact of malaria over the last 10 years, the emergence of multi-drug resistant parasites is a major threat to further advances. There is an urgent and ongoing need for the development of new antimalarial drugs, especially compounds that have completely novel mechanisms of action from those currently in use, and compounds that simultaneously target the two major causative agents of malaria Plasmodium falciparumand P. vivax. One highly potent novel target is the pan-Plasmodiumprotein export trafficking complex known as PTEX, originally identified by our team. We have demonstrated that PTEX is obligatory for parasite growth, indeed even mild perturbation of PTEX function rapidly kills parasites in the blood. The PTEX complex forms protein translocating pores around intracellular parasites through which parasite proteins gain access to the cytoplasm of their erythrocyte hosts. Exported proteins modify their erythrocyte cells enabling parasites to reproduce and avoid host immunity. One aspect of protein translocation that is little understood is how the exported proteins are refolded after they are extruded into the erythrocyte compartment by PTEX. Some form of refolding is presumably required to functionally activate exported proteins so they can perform their roles. In this project we aim to trap exported reporter proteins in the process of being exported while protein refolding factors are at work attempting to refold their client proteins. These refolding proteins will then be captured and identified so their functions can be investigated by reverse genetic and chemical approaches. Laboratory techniques will include parasite culture, protein purification, mass spectrometry and parasite molecular biology.
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Research NodeBurnet Institute
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