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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.
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.
The body’s normal function depends upon maintaining energy balance matching demand and supply. The body senses its energy status by monitoring metabolite concentrations. I have discovered a metabolite that controls multiple enzymes critical for energy homeostasis and appetite in the body that may provide new approaches to tackle obesity related disease. I have found the metabolite-binding pocket in many proteins and it may represent a major new regulatory network.
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.
Preventing The Evolution Of Transmissible Nitroimidazole Resistance In Mycobacterium Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$664,463.00
Summary
Tuberculosis kills more people than any other infectious disease. Unfortunately, the drugs available to us to treat TB are losing their efficacy due to the evolution of drug resistance. A new class of drugs, nitroimidazoles, has been developed, but there is a risk that the bacterium that causes TB will develop resistance to these compounds too. We will identify resistance mutations before they occur in the wild, to help identify them and find new compounds for which resistance cannot develop.
Discovering How A Novel Anti-malarial Drug Series Rapidly Kills Parasites
Funder
National Health and Medical Research Council
Funding Amount
$672,971.00
Summary
We have developed a new set of highly potent anti-malarial drugs but we do not know how they work. Identifying how these compounds work is important for improving their effectiveness and safety. We will discover how these drugs kill parasites by using a number of cutting edge methods that could also be useful for discovering how other drugs work. Data generated will progress these compounds along the drug development pipeline which urgently needs a constant supply of new antimalarials.
DsbA Foldases From Multidrug Resistant Pathogens As Targets For New Antimicrobials
Funder
National Health and Medical Research Council
Funding Amount
$743,401.00
Summary
Bacteria that cause common human infections, such as cystitis and diarrhoea, are now resistant to many antibiotics. If no action is taken, by 2050 antibiotic resistant infections will kill more people each year than cancer. This project aims to address this global public health crisis by characterising promising new bacterial targets and inhibitors designed to disarm multidrug resistant pathogens. Longer term this work could provide new infection therapies that are urgently needed.