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.
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.
Defining The Mechanisms Of Action For Ozonide Antimalarials
Funder
National Health and Medical Research Council
Funding Amount
$668,152.00
Summary
Deadly malaria parasites have emerged that are resistant to all classes of approved drugs. Ozonides are a new class of medicines recently approved for malaria, and provide a much-needed treatment option for multi-drug resistant infections. However, the mode of action and potential for cross-resistance is poorly understood. This project will use modern analytical techniques to measure the impact of ozonides on parasite biochemistry to reveal mechanisms involved in drug action and resistance.
Validation Of Formyl Peptide Receptor (FPR)2 As A Target For New Anti-cancer Drugs
Funder
National Health and Medical Research Council
Funding Amount
$588,529.00
Summary
Treatment of breast and other cancers is making incremental improvements, but premature death from this disease and its recurrence in some women after a long period of remission are not adequately treated by current drugs. New work has identified a target called FPR2 that could be used to guide the development of novel drugs. The current project seeks to validate the new drug target, before resource intensive efforts are made to find suitable drugs.
Discovery Of Active Metabolic Pathways Suitable For Drug Targeting In Trypanosoma Brucei
Funder
National Health and Medical Research Council
Funding Amount
$485,517.00
Summary
Sleeping Sickness is a parasitic disease affecting many of the world’s poorest countries, and is fatal if left untreated. The aim of this project is to identify new metabolic pathways in the parasite that causes Sleeping Sickness, and to investigate how drugs interfere with parasite metabolism. This will provide the basis for new drug discovery efforts and facilitate the development of new medicines for Sleeping Sickness.
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.
Stimulant laxatives are widely used and usually very effective in the short term, but how they work is very poorly understood. Our recent work has shown that they selectively excite sensory pathways from the colon which then trigger defaecation. This points to an undiscovered mechanism that potently affects colonic sensation and motility. This is likely to be a target for new treatments for other colonic disorders such as Irritable bowel syndrome and faecal incontinence.
Melanotransferrin: A “Missing Link” And A Novel Pharmacological Target For Treatment
Funder
National Health and Medical Research Council
Funding Amount
$613,848.00
Summary
Despite >30 years of research, the precise function of the protein, melanotransferrin (MTf), is unknown. However, we have breakthrough evidence that MTf stimulates WNT signalling as a major driver in cancer progression. We will investigate this hypothesis, which will underpin new cancer therapies. Indeed, we designed a new class of drugs that target the WNT pathway via up-regulating the WNT inhibitor, NDRG1. This drug (DpC) inhibits MTf expression to block tumour cell growth and metastasis.
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.