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.
Functional Characterisation Of The Essential Aurora Kinase Family In The Human Malaria Parasite Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$511,699.00
Summary
Malaria is responsible for 300 million new clinical cases and 650.000 deaths yearly. There is no vaccine and drug resistance is a growing problem. Protein kinases are key players in most cell functions and recognised potential drug targets. We will focus on the essential Plasmodium Aurora mitotic kinases, by localising them inside the parasite, identifying their binding partners and deciphering their in vivo function, to provide a strong biology basis for downstream drug discovery research.
Targeting The Plasmodium Falciparum Metalloaminopeptidases For Development Of New Antimalarial Agents
Funder
National Health and Medical Research Council
Funding Amount
$565,507.00
Summary
Each year 1-2 million people will die from malaria. The prevention and treatment of malaria is becoming increasingly difficult due to the spread of drug-resistance. There is an urgent need for next generation of antimalarials with new modes of action. This project will develop new antimalarial agents against the malarial aminopeptidase drug targets.
Generating An Effective Vaccine Response Against The Intrinsically Unstructured Malaria Antigen Merozoite Surface Protein 2
Funder
National Health and Medical Research Council
Funding Amount
$678,774.00
Summary
The malaria surface protein MSP2 is a promising candidate for inclusion in a malaria vaccine, having shown evidence of protection in phase IIb studies. Our goals are to identify the structural basis for the differential induction of human immune responses to native and recombinant MSP2 and to utilise this information to generate an MSP2 vaccine able to evoke a more effective anti-malarial response.
In Vitro And In Vivo Investigation Of Actin Regulation In The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$92,294.00
Summary
Malaria parasites move in a unique way. They move across cell surfaces and infect human cells using a unique molecular motor that allows them to, literally, glide. The research proposal outlined here is focused on understanding a key part of the motor – the dynamic protein actin – and by understanding how it is regulated develop new potential targets for novel drugs that might stop movement and, therefore, help prevent or treat malaria disease.
Investigating Cytoskeletal Dynamics Across The Lifecycle Of The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$387,741.00
Summary
During its lifecycle the malaria parasite must cross tissues and invade cells in two very different hosts - humans and mosquitos. Although the molecules that drive this process are known, we know nothing about their dynamics in live parasites. Here, we will use state-of-the art microscopy and genetics to dissect parasite motility, tracking proteins in the parasite cell on their journey from human host through to the mosquito - utilising the first Australian malaria-dedicated insectary.
A New Class Of Anti-Malarial Agents Targetting Apical Membrane Antigen
Funder
National Health and Medical Research Council
Funding Amount
$597,598.00
Summary
Malaria is a major global health problem that imposes a substantial burden on the world’s most vulnerable societies. The invasion of host cells by malaria parasites represents an attractive target for therapeutic intervention, and Apical Membrane Antigen 1 (AMA1) plays an essential role in this process. Agents that bind to a key interaction site on AMA1 prevent host cell invasion and thus represent starting points for the development of a new class of anti-malarial drugs.