Protecting The Efficacy Of Antimalarial Therapies With Novel Approaches To Suppress The Emergence Of Drug Resistance
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
The global campaign to eliminate malaria is under serious threat from the continuing emergence and spread of Plasmodium falciparum parasites resistant to antimalarial drugs. However in acquiring resistance to one drug, the parasite can become more susceptible to other antimalarials. This project aims to 1) test the ability of drug pairs with opposing selection forces to suppress resistance in vitro and 2) define the physiological and molecular basis of these opposing evolutionary forces.
Plasmodium Knowlesi As A Genetic Model For Plasmodium Vivax Drug Resistance
Funder
National Health and Medical Research Council
Funding Amount
$417,193.00
Summary
Two different Plasmodium parasites cause the majority of malaria worldwide. However, one type, P. vivax, is unable to be cultured in the laboratory and therefore has been poorly studied. Drug resistance has been observed but the underlying causes are poorly understood. We propose to use a closely related parasite, P. knowlesi, as a model to understand drug resistance mechanisms. This knowledge will be used to follow resistance in the field and direct policy of the most appropriate treatment.
Exported Epoxide Hydrolases Of The Malaria Parasite, Plasmodium Falciparum, And Their Role In Modulation Of Host Vasoregulation
Funder
National Health and Medical Research Council
Funding Amount
$342,054.00
Summary
The major aim of this study is to define the physiological role of the parasite EHs, and to establish whether they modulate levels of EETs within infected erythrocytes. I will examine if infected erythrocytes have impaired vasoactive properties and also determine if this pathway has therapeutic potential
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.
Improving Malaria Elimination Strategies With Genomics: Tackling The Unique Problems Posed By Plasmodium Vivax, And P. Falciparum Drug Resistance
Funder
National Health and Medical Research Council
Funding Amount
$327,193.00
Summary
Malaria parasites are becoming resistant to drugs, and some types can avoid treatment by hiding in the liver and recurring months later. Variation in human genes can also mean that some drugs are dangerous to certain people, or won’t work. DNA sequencing will allow us to understand the interplay between parasite and host genetics and the efficacy of drugs in the population, allowing us to provide ‘personalised’ treatments in that region.
Insights Into The Biology Of The Carcinogenic Blood Fluke, Schistosoma Haematobium – A First Response To The Wake-up Call
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
Schistosoma haematobium is a seriously neglected parasite that infects > 100 million people. Chronic infection severely affects the urino-genital system and causes malignant bladder cancer. Advanced technologies will be used to explore, for the first time, the molecular biology of this parasite, design new strategies to fight this insidious pathogen and understand how it induces cancer.
Export Of Effector Proteins By P. Falciparum To The Infected Erythrocyte.
Funder
National Health and Medical Research Council
Funding Amount
$196,582.00
Summary
Infection by the malaria parasite has lethal consequences for humans. In order to survive the parasite exports hundreds of proteins to commandeer the erythrocyte. A translocon that mediates such export has been identified and important questions remain unanswered. In this research, I aim to determine the function of one of the major translocon components for export of proteins to the erythrocyte (EXP2) and through this process determine if it is a viable target for anti-malarial drug development ....Infection by the malaria parasite has lethal consequences for humans. In order to survive the parasite exports hundreds of proteins to commandeer the erythrocyte. A translocon that mediates such export has been identified and important questions remain unanswered. In this research, I aim to determine the function of one of the major translocon components for export of proteins to the erythrocyte (EXP2) and through this process determine if it is a viable target for anti-malarial drug development.Read moreRead less