Trafficking of the cytoadherence-mediating protein to the host cell surface in malaria parasite-infected erythrocytes

Funded Activity Summary

Malaria kills between 1 and 3 million children each year. In addition, the disease debilitates the adult population in malaria-endemic areas, thereby contributing to the cycle of poverty in many third world countries. As resistance to existing antimalarial drugs increases, there is an urgent need to understand the workings of the parasite at a molecular level to enable the development of alternative antimalarial strategies. During part of its life cycle, the malaria parasite infects the red blood cells of its human host. The parasite transports proteins to the red blood cell membrane so as to modify the properties of its adopted cellular residence. The parasite proteins that are deposited at or in the red blood cell membrane increase the leakiness and the stickiness of the parasitised red blood cells. This allows more efficient uptake of nutrients and allows the parasitised red blood cells to adhere to blood vessel walls, thereby avoiding passage through the spleen. Adherence of parasitised red blood cells to capillaries in the brain and the placenta is thought to lead to the development of the complications known as 'cerebral' and 'placental' malaria. These complications are responsible for the deaths of many children and pregnant women. We propose to use cell biology techniques to introduce foreign genes into malaria parasite-infected red blood cells to unravel the details of the molecular machinery and the ticketing system that the parasite uses to traffic its virulence proteins to their correct destinations. These studies could potentially lead to the development of novel intervention strategies. For example, if it were possible to decrease the levels of surface expression of a protein known as PfEMP1, adhesion of infected red blood cells would be inhibited. This would greatly decrease the impact of this important human pathogen.

Funded Activity Details

Start Date: 01-01-2007

End Date: 01-01-2009

Funding Scheme: NHMRC Project Grants

Funding Amount: $547,315.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Plasmodium falciparum | cerebral malaria | cytoadherence | drug resistance | laser scanning confocal microscopy | malaria | placental malaria | protein trafficking | transfection

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