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.
Elucidating The Mechanisms Of Action Of And Resistance To Endoperoxide Antimalarials
Funder
National Health and Medical Research Council
Funding Amount
$716,755.00
Summary
Artemisinin-based antimalarials (ARTs) save hundreds of thousands of lives every year. Unfortunately resistance of P. falciparum to ART is now emerging in South East Asia and it is critical to know how and why. We will determine what is different about resistant parasites and will develop assays to monitor drug resistance in the field. We have found that the immature form of the malaria parasite is more resistant to ARTs, which helps explain resistance. We will build on this to develop new targe ....Artemisinin-based antimalarials (ARTs) save hundreds of thousands of lives every year. Unfortunately resistance of P. falciparum to ART is now emerging in South East Asia and it is critical to know how and why. We will determine what is different about resistant parasites and will develop assays to monitor drug resistance in the field. We have found that the immature form of the malaria parasite is more resistant to ARTs, which helps explain resistance. We will build on this to develop new targetted treatments.Read moreRead less
Functional Resolution Of PTEX, The Exporter Of Virulence Factors In Malaria Parasites.
Funder
National Health and Medical Research Council
Funding Amount
$625,212.00
Summary
Almost half a million people die each year of malaria and nearly half the world’s population are at risk. To eliminate malaria this century we will need new drugs and vaccine to fight the disease. One potential drug target are the molecular gateways called PTEX, that are used by parasites to export virulence proteins into their human host cells. This grant aims to understand how the PTEX molecular machines work so we can develop new drugs to block them and kill the parasites.
Griseofulvin, A Novel Host-directed Antimalarial Drug
Funder
National Health and Medical Research Council
Funding Amount
$461,551.00
Summary
This grant is for a Phase II clinical trial to test an FDA & TGA approved drug for a new use as an antimalarial drug. The parasite uses an enzyme from the human RBC to help it replicate & early trials show this drug appears to disrupt the life cycle of the parasite. This Phase II clinical trial will test the drug on human subjects, & if successful, the drug will be a new and novel way in which to treat and prevent malarial infections in humans.
Malaria In Pregnancy: Exposure, Immunity And Complications
Funder
National Health and Medical Research Council
Funding Amount
$549,723.00
Summary
Increasing malaria control efforts may lead to lack of exposure needed to develop immunity. We will use plasma samples from Africa, PNG and Asia, and measures of immunity we have developed, to discover (1) which are the most important protective immune responses and (2) how are these affected by changing exposure or new drugs. Overall, we hope to identify markers of protective immunity that can be used to identify women at most risk of malaria in pregnancy and its complications
The Structural Resolution Of PTEX, The Translocon Of Virulence Proteins And Malaria Parasites.
Funder
National Health and Medical Research Council
Funding Amount
$561,028.00
Summary
The extraordinary virulence of malaria parasites is in part due to their ability to export hundreds of proteins into their red blood cell hosts that help them obtain nutrients and avoid the immune system. Recently we discovered the molecular machine that exports proteins into the host cell and we now wish to establish how it works so drugs can be tailored to block the machine and kill the parasites.
Functional Characterisation Of The Malaria Protein Export Machinery
Funder
National Health and Medical Research Council
Funding Amount
$556,104.00
Summary
The ability of malaria parasites to cause one of the most devastating infectious diseases of humans is in part due to their ability to export hundreds of proteins into their host red blood cells to obtain nutrients, evade the immune system and contribute to associated pathologies. Recently, we discovered the molecular machine that exports proteins into the host cell and so now we wish to establish how it works so that drugs can be tailored to block it to kill these parasites.
Dynamics Of Malaria Transmission Stages In Host And Vector: Bottlenecks And Their Impact Transmission And Parasite Population Diversity
Funder
National Health and Medical Research Council
Funding Amount
$780,554.00
Summary
The adoption of malaria elimination as the long-term goal requires malaria programs to shift their focus from controlling the burden of malaria disease & deaths to the interruption of transmission itself. This will be impossible without an improved understanding of the processes involved and novel tools directly targeting transmission. We therefore plan to conduct an in-depth examination of bottlenecks to malaria transmission in Papua New Guinea, the country with the highest malaria burden in ou ....The adoption of malaria elimination as the long-term goal requires malaria programs to shift their focus from controlling the burden of malaria disease & deaths to the interruption of transmission itself. This will be impossible without an improved understanding of the processes involved and novel tools directly targeting transmission. We therefore plan to conduct an in-depth examination of bottlenecks to malaria transmission in Papua New Guinea, the country with the highest malaria burden in our region.Read moreRead less
The Control And Regulatory Mechanisms Of Artemisinin Induced Dormancy In P. Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$495,552.00
Summary
Malaria is a major global health problem and can only be reliably treated with artemisinin combinations in many areas due to widespread of drug resistance. However a proportion of parasites appear to be able to avoid the lethal effects of the drug by becoming “dormant” following exposure. They resume growth after the drug is wanned, a feature which is reminisent to cell cycle arrest. This study investigates the role of cell cycle machinery in dormancy following arteminsinin treatment.
Export Of PfEMP1, The Major Virulence Protein Of P. Falciparum, To The Parasite-infected Erythrocyte Surface
Funder
National Health and Medical Research Council
Funding Amount
$588,532.00
Summary
The malaria parasite infects red blood cells in the human host and initiates major remodelling. This involves export of a major virulence protein to the surface of the red blood cell. This research seeks to understand how the parasite exports this protein, a key determinant of disease.