Use of novel transfection protocols to study protein trafficking in malaria-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 erythrocytes of its human host. The parasite transports proteins to the erythrocyte membrane so as to modify the properties of its adopted cellular residence. The parasite proteins that are deposited at or in the erythrocyte membrane increase the leakiness and the stickiness of the parasitised erythrocytes. This allows more efficient uptake of nutrients and allows the parasitised erythrocytes to adhere to blood vessel walls, thereby avoiding passage through the spleen. Adherence of parasitised erythrocytes to capillaries in the brain is thought to lead to the development of the complication known as cerebral malaria. This complication is responsible for most of the deaths due to malaria. In order to traffic the adherence proteins to the erythrocyte surface, the parasite establishes a novel transport pathway for moving proteins across the erythrocyte cytoplasm. As the uninfected erythrocyte has no means, nor requirement, for moving proteins, this novel transport mechanism may represent a target for drugs that kill the malaria parasite without being toxic to humans. The pathways for the movement of proteins around the infected erythrocyte are largely unknown. We propose to use techniques to introduce foreign genes into malaria-infected erythrocytes to unravel the details of the molecular machinery and the ticketing system that the parasite uses to traffic proteins to their correct destinations in its adopted home.

Funded Activity Details

Start Date: 01-01-2001

End Date: 01-01-2003

Funding Scheme: NHMRC Project Grants

Funding Amount: $211,527.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Protein Targeting And Signal Transduction

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

cerebral malaria | confocal fluorescence microscopy | drug resistance | immunolocalisation | malaria | plasmodium falciparum | protein trafficking | transfection

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