Breaking Malaria's Lethal Grip: Targeting The Assembly Of An Adhesive Complex On Infected Red Blood Cells
Funder
National Health and Medical Research Council
Funding Amount
$817,426.00
Summary
The malaria parasite, Plasmodium falciparum, infects the red blood cells of its human victims. It causes them to stick to blood vessel walls in the brain, causing severe cerebral complications and death. Adhesion is mediated by a Velcro-like protein that is presented at the red blood cell surface. This project will fully elucidate the pathway for trafficking of the adhesion protein to the red blood cell surface with a view to finding new ways of interfering with malaria disease.
I am a microbiologist with expertise in virology and parasitology. My principal focus is understand the pathogenic processes adopted by the human malaria parasite Plasmodium falciparum
Trafficking Of The Major Virulence Protein To The Host Cell Surface In Malaria Parasite-infected Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$658,164.00
Summary
The malaria parasite infects human red blood cells and causes them to stick to blood vessels in the brain, inducing coma. This causes the deaths of ~2 million children each year. We will use cell biology techniques to manipulate malaria parasites to unravel the details of the molecular ticketing system that the parasite uses to get its adhesive proteins onto the red blood cell surface. The ability to interfere with this process would greatly decrease the impact of this major human pathogen.
Trafficking Of The Cytoadherence-mediating Protein To The Host Cell Surface In Malaria Parasite-infected Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$547,315.00
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 bloo ....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.Read moreRead less
Use Of Novel Transfection Protocols To Study Protein Trafficking In Malaria-infected Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
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 erythroc ....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.Read moreRead less