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.
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.
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.
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.
Investigating The Therapeutic Potential Of FTY720 For Human African Trypanosomiasis
Funder
National Health and Medical Research Council
Funding Amount
$653,736.00
Summary
FTY720, is a drug currently used to treat multiple sclerosis, which we have shown is also be able to kill the parasite responsible for African sleeping sickness, Trypanosomes. We aim to identify the target the drug acts on in the parasite to have its affect. Our objective is to improve the activity further by chemical modification to produce a potent, orally available and well characterised, non-toxic drug suitable for preclinical development.
The WHO estimates there were ~189 million clinical cases & 584,000 malaria-related deaths in 2013. This translates to ~1,600 child deaths daily. There is no licensed malaria vaccine & all available drugs are associated with resistant parasites. This enormous health issue is driving the search for new therapies. We address this issue by identifying new drug candidates for malaria prevention, with unique modes of action to treatment drugs in order to overcome issues of parasite drug resistance.
New Antimalarial Drug Leads Targeting Multiple Species And Life Cycle Stages
Funder
National Health and Medical Research Council
Funding Amount
$818,477.00
Summary
Malaria causes ~200 million clinical cases and >430,000 deaths annually. Prevention and treatment relies on drugs, however malaria parasite drug resistance is an enormous problem. To address this issue, and aim towards eliminating malaria, we need to develop new drugs. This project addresses this important health need by investigating the ability of new chemical compounds, developed at CSIRO, to kill human-infecting malaria parasites during different parts of their complicated lifecycles.
Metabolomic Analysis Of Plasmodum Falciparum And Mode Of Action Of Antimalarial Compounds
Funder
National Health and Medical Research Council
Funding Amount
$917,196.00
Summary
There is an urgent need to develop new drugs to treat malaria, one of the most important diseases to afflict humanity. We have developed new analytical approaches for measuring parasite metabolism while they live inside host cells. These approaches will be used to identify metabolic pathways that are essential for parasite infectivity and to understand the mode of action of new classes of antimalarial compounds
Targeting Schistosome Calcium Signalling To Improve And Broaden Praziquantel Efficacy
Funder
National Health and Medical Research Council
Funding Amount
$481,661.00
Summary
Schistosomiasis is caused by parasitic worms, treatment relies solely on praziquantel (PZQ). Schistosomes respond and recover from PZQ exposure through modulation of the gene CamKII. We will target this gene to both increase and extend the efficacy of PZQ in both adult parasites and in refractory juvenile parasites. Research will expand into assaying CamKII inhibitors to maximise effectiveness and take this work into animal models of this disease.
Chromatin Dynamics During Sexual Differentiation In The Malaria Parasite P. Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$535,858.00
Summary
Inhibiting malaria transmission is a critical step towards global eradication of this deadly disease. This proposal aims to understand the mechanisms regulating the expression of genes which control the differentiation of the transmission stages of malaria parasites. Such pathways are prime targets for novel anti-malarial drugs.