Functional Analyses Of The Major Merozoite Surface Protein Of Malaria Parasites
Funder
National Health and Medical Research Council
Funding Amount
$70,285.00
Summary
In this project we aim to learn about the function of one of the leading malaria vaccine candidates, merozoite surface protein 1 (MSP-1). Although a promising candidate, little is known about the role of this protein in the invasion by parasites of red blood cells or of the likelihood that the parasites will adapt to avoid vaccines based on MSP-1. To address these issues we propose to use the powerful new technology of parasite transfection, that is the ability to insert DNA into parasites to sp ....In this project we aim to learn about the function of one of the leading malaria vaccine candidates, merozoite surface protein 1 (MSP-1). Although a promising candidate, little is known about the role of this protein in the invasion by parasites of red blood cells or of the likelihood that the parasites will adapt to avoid vaccines based on MSP-1. To address these issues we propose to use the powerful new technology of parasite transfection, that is the ability to insert DNA into parasites to specifically alter its genetic code. We have pioneered this technology and have developed many of the most effective tools for the process. Insight gained from these studies is likely to influence significantly the design and potential uses of MSP-1 as a vaccine to control malaria.Read moreRead less
The Role Of Phosphorylation And Signalling For Invasion Of Plasmodium Falciparum Into Human Erythrocytes.
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
The intracellular signals that govern Plasmodium falciparum malaria invasion of the red blood cell are poorly understood. It is likely calcium dependent phosphorylation leads to recruitment and activation of a cascade of proteins. This study combines a break-through in purification of viable P. falciparum merozoites with proteomic analysis of phosphorylation states to assess intracellular signalling. It is expected the processes identified will be unique to P. falciparum and targetable by drugs.
Malaria is a major global health problem. The protein AMA1 plays a key role in the invasion of host cells by malaria parasites, and agents that inhibit this interaction prevent host cell invasion and thus represent leads for the development of anti-malarial drugs. We have identified a number of chemical scaffolds that target a key site on AMA1. In this project we will optimize these leads to generate potent ligands for this site and evaluate the efficacy of these ligands as anti-malarial agents.