Biochemical Investigation Of Ubiquitination By The Fanconi Anaemia Pathway
Funder
National Health and Medical Research Council
Funding Amount
$603,447.00
Summary
Fanconi anaemia is an inherited disorder with greatly elevated risk of leukaemia and cancers. The causal genes are ‘tumour suppressors’ that protect us from cancer by a complex function in repair of damage to our DNA. This study aims to understand how this DNA repair function protects us from cancer, and may influence some forms of new forms of cancer treatment.
Targeting Cancer-initiating Cells With DNA Methyltransferase Inhibitors: Single-cell Analysis To Decipher Molecular Mechanisms And Improve Efficacy.
Funder
National Health and Medical Research Council
Funding Amount
$175,000.00
Summary
Certain cancer cells, termed cancer-initiating cells (CICs), have special properties allowing them to drive cancer growth and disease progression. These cells are particularly sensitive to low-dose treatment with drugs called DNA methyltransferase inhibitors. Using cutting-edge "single-cell" technologies this project will determine how these drugs target CICs and identify new ways to increase treatment efficacy. This work will identify new clinical opportunities for prevention of cancer relapse.
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.
Dissecting The Pathogenic Triad Of Enteric Pathogens: Assembly, Structure And Function Of Autotransporter Proteases
Funder
National Health and Medical Research Council
Funding Amount
$639,428.00
Summary
SPATEs are proteases secreted by many enteric bacteria that contribute to their pathogenic potential by damaging host tissues and evading the host immune response. We aim to study the structural basis of their assembly and biological function. The information we gain will assist the development of new diagnostics and improved therapies for enteric infections.
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.
Octapeptin-based Antibiotics Against Multi-drug Resistant Gram-negative Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$767,504.00
Summary
Infectious disease is a leading cause of death, and the emergence of "superbugs" in the community and hospitals is of grave concern. We have resurrected a ‘forgotten’ antibiotic from the 1970s that kills superbugs causing pneumonia, skin and urinary track infections; diseases that cause death and discomfort for thousands of Australians today. We will determine how the original antibiotic works against superbugs, and use this information to design better drugs for the future.
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.
Potent Lipoglycopeptide Antibiotics Against C. Difficile
Funder
National Health and Medical Research Council
Funding Amount
$750,411.00
Summary
In some people C. difficile bacteria naturally reside in the gut. Other people accidentally ingest spores of the bacteria while they are patients in a hospital or nursing home. Sometimes, broad-spectrum antibiotics used to treat an infection also kill healthy gut bacteria. The gut then becomes overrun with C. difficile, causing diarrhoea and pain, and sometimes death. We will investigate the use of a new potent antibiotic, vancapticin, to kill C. difficle and prevent relapse of infection.
Lipidomic Analysis Of The FIELD Trial: Mechanism Of Action And Prediction Of Response To Fenofibrate Treatment In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$643,323.00
Summary
Patients with type 2 diabetes have abnormal blood lipids leading to an increased risk of cardiovascular disease. This risk can be decreased by fenofibrate treatment. However, not all patients show the same response to fenofibrate and so it is not clear who will benefit and who will not benefit from treatment. In this project we will develop a test to identify those patients who respond to and benefit from fenofibrate treatment. This will lead to the better outcomes for patients.
Development Of New Anticancer Drugs Using Sortase-mediated Ligation
Funder
National Health and Medical Research Council
Funding Amount
$618,274.00
Summary
There is a great need for new cancer treatments. We are developing cyclic peptides as the next generation of safe and effective cancer drugs. Cyclic peptides, unlike their linear counterparts, display high stability and oral bioavailability, as well as high solubility and negligible immune response. One of the hurdles is the cyclisation process and we aim to develop enzyme-mediated cyclisation as a convenient and cost effective method for cyclic peptide production.