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.
Proteasome Inhibitors As Reversers Of Resistance To Artemisinin-based Antimalarials
Funder
National Health and Medical Research Council
Funding Amount
$473,534.00
Summary
Current antimalarial control is highly dependent on Artemisinin Combination Therapy (ACTs), which makes recent reports of decreased clinical efficacy of artemisinins extremely concerning. This project will develop proteasome inhibitors to synergise the activity of artemisinins - effectively reversing resistance. We will confirm that the selected compounds have good bioavailability, low cytotoxicity in human cell lines and efficacy in mouse models of malaria.
The transmission of malaria is dependent on gametocytes, the sexual stages of parasite development that are taken up by mosquitoes when feeding on an infected person. While gametocytes are not responsible for disease symptoms, it is clear that malaria eradication is not be possible without an understanding of their biology and the tools to prevent transmission. My research focuses on understanding the biology of gametocytes and identifying new drug targets for transmission blocking strategies.
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.
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.
Targeting An Ion Pump In The Malaria Parasite With Multiple Compound Classes
Funder
National Health and Medical Research Council
Funding Amount
$384,686.00
Summary
Large-scale antimalarial drug screening projects have identified three different classes of compound that kill the malaria parasite at extremely low doses and which hold real promise as next-generation antimalarials. Genetic evidence, as well as preliminary data from our own lab, has led us to the hypothesis that all three compound classes exert their antimalarial effect by blocking a molecular ion pump on the parasite surface. The aim of this study is to test this.
Parasitic infections are a significant global health problem, resulting in more than a million deaths annually. Unfortunately there is no licensed vaccine available for any human parasitic infection, and in many cases current drugs suffer from issues of parasite drug resistance. To address this problem this project brings together leading researchers from the European Union, Brazil, and Australia to discover and develop new types of drugs for four major human parasitic diseases: schistosomiasis, ....Parasitic infections are a significant global health problem, resulting in more than a million deaths annually. Unfortunately there is no licensed vaccine available for any human parasitic infection, and in many cases current drugs suffer from issues of parasite drug resistance. To address this problem this project brings together leading researchers from the European Union, Brazil, and Australia to discover and develop new types of drugs for four major human parasitic diseases: schistosomiasis, leishmaniasis, Chagas disease and malaria.Read moreRead less
Functional Studies On Two Essential Rhoptry Proteins Of The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$470,894.00
Summary
Malaria is one of the most important and deadly infectious diseases in the world, causing 250 million cases and nearly one million deaths each year. Traditionally, drugs and insecticides have been used to treat the disease and control its spread. They have become much less effective and there now exist untreatable cases of malaria. Alternative control measures are urgently needed. An understanding of how proteins essential to parasite survival operate may identify novel targets for therapeutic i ....Malaria is one of the most important and deadly infectious diseases in the world, causing 250 million cases and nearly one million deaths each year. Traditionally, drugs and insecticides have been used to treat the disease and control its spread. They have become much less effective and there now exist untreatable cases of malaria. Alternative control measures are urgently needed. An understanding of how proteins essential to parasite survival operate may identify novel targets for therapeutic intervention against this devastating disease.Read moreRead less
Phenotypic Characterization Of Chloroquine Resistance In Plasmodia
Funder
National Health and Medical Research Council
Funding Amount
$585,473.00
Summary
In the Asia-Pacific region, vivax malaria is becoming the dominant species of infection. The emergence and spread of chloroquine resistant strains of P. vivax threatens malaria control and elimination efforts. This project aims to elucidate fundamental aspects of chloroquine resistance in non-falciparum malaria and identify novel therapeutic options. We will develop novel tests that will help national malaria control programs to monitor declining activity of standard anti-malarial drugs.
Developing Synergisers Of The Antimalarial Drug, Chloroquine, For The Treatment Of Chloroquine-resistant P. Falciparum.
Funder
National Health and Medical Research Council
Funding Amount
$243,000.00
Summary
Malaria is a debilitating parasitic disease that is responsible for the deaths of about two million children each year. As drugs, such as chloroquine, become increasingly useless due to the development of parasite resistance, there is an urgent need to understand the mode of action of and the molecular basis of resistance to existing antimalarials and to design affordable treatments that can replace chloroquine. It is known that some compounds, that have only poor antimalarial activity themselve ....Malaria is a debilitating parasitic disease that is responsible for the deaths of about two million children each year. As drugs, such as chloroquine, become increasingly useless due to the development of parasite resistance, there is an urgent need to understand the mode of action of and the molecular basis of resistance to existing antimalarials and to design affordable treatments that can replace chloroquine. It is known that some compounds, that have only poor antimalarial activity themselves, can synergise the action of chloroquine. This may involve the inhibition of the activity of proteins that directly or indirectly extrude chloroquine from its site of action in the parasite's digestive apparatus. Unfortunately, thechloroquine synergisers examined to date have been too toxic to be useful in vivo. In preliminary studies we have identified some compounds that would be suitable for use in malaria patients, including a widely used antimalarial drug, primaquine, that can synergise the activity of chloroquine against chloroquine-resistant parasites. We will attempt to understand the molecular basis of this interaction. This will allow us to define optimal combinations of chloroquine and a resistance-reversing quinoline for use treating malaria. This could extend the clinical life of this important antimalarial drug. The information obtained may also help to design novel antimalarial drugs.Read moreRead less