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.
We will investigate malaria, a parasitic disease that kills over 600,000 people a year. We will explore how the parasite identifies, invades and remodels the host cells in which it lives, scavenging nutrients and hiding from the immune system. We will characterize the proteins involved in these critical events, as they are potential targets for drugs and vaccines. We will study how parasites cause disease and how the host responds to infection.
My research team is focused on human parasites of major relevance to the Australian water industry and/or global public health. Our primary focus is the use of advanced technologies to improve understanding of these parasites and to utilize this information to underpin development of new drugs to treat them and novel diagnostic tests to improve their control.
Retargeting The Antibiotic Azithromycin As An Antimalarial With Dual Modality.
Funder
National Health and Medical Research Council
Funding Amount
$773,613.00
Summary
Malaria parasites resistant to first-line treatments continue to spread in South East Asia. New drugs need to be developed urgently to ensure alternative treatment strategies are available. We will retarget the safe and widely used antibiotic azithromycin as an antimalarial with dual modalities against parasite invasion and growth inside the host red blood cell. This strategy has significant potential to increase drug efficacy while reducing the chances for the development of resistance.
Understanding And Targeting Coenzyme A Biosynthesis And Utilisation In Plasmodium Falciparum.
Funder
National Health and Medical Research Council
Funding Amount
$556,114.00
Summary
This grant describes a series of studies designed to understand how the human malaria parasite P. falciparum metabolises vitamin B5, an essential molecule for the parasite. We will also carry out experiments to determine how a new series of vitamin B5 analogues we have developed kill the parasite and aim to start developing these compounds into new and much needed antimalarial medications.
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
Interactions Between The Malaria Parasite's Chloroquine Resistance Transporter And Antimalarial Drugs
Funder
National Health and Medical Research Council
Funding Amount
$485,641.00
Summary
The malaria parasite is a single-celled organism which invades the red blood cells of its host. The aim of this project is to characterize the parasite protein responsible for conferring resistance to chloroquine, and to study its interaction with other antimalarial drugs. The parasite's susceptibility to chloroquine, and other drugs, is altered by small changes in this protein. This work will advance our understanding of the increasingly widespread phenomenon of antimalarial drug resistance.
Combating Giardiasis By Investigating New Potent Compound Series As Leads For Improved Treatment Options
Funder
National Health and Medical Research Council
Funding Amount
$776,028.00
Summary
Giardia parasites infect ~1 billion people globally and are responsible for significant morbidity and disadvantage. There is no licensed vaccine and current treatment options are inadequate, resulting in poor compliance, treatment failures, rapid re-infection and drug resistance. New therapies are needed to combat this parasite and improve the health of millions world-wide. We will address this issue by investigating new drug candidates for the treatment of Giardia infections.
The Na+-H+ Exchanger And H+-pumping Pyrophosphatases Of The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$664,604.00
Summary
Malaria is an infectious disease caused by a single-celled parasite. The disease kills up to 2 million people each year and the parasite is becoming increasingly resistant to available drugs. This work focuses on the mechanisms by which the parasite controls its internal ion concentrations. These mechanisms may be new drug targets, and they may also play a role in antimalarial drug resistance. For both of these reasons it is important that we understand them.
In 2013 there were ~200 million clinical cases of malaria, causing ~600,000 deaths. All antimalarial drugs are now associated with malaria parasite resistance. Thus, new therapies are urgently needed, including new drugs to prevent this disease. We have made the exciting discovery that an existing antimalarial drug can kill malaria parasites in a unique, previously unknown, manner. Here, we will investigate how this occurs and develop new drug candidates for malaria prevention.