Improving the function of GABA-A receptors is a key property of several classes of clinically important drugs including benzodiazepines and many anticonvulsants. However, the binding sites and molecular mechanisms of these drugs remain poorly understood. Using compounds similar to those in green tea, we will determine the molecular mechanism of these drugs. This understanding will lead to the development of better drugs for treatment of anxiety, depression, epilepsy, insomnia & schizophrenia.
Developing Species-specific, Structure-targeting Peptides As A Novel Class Of Antibiotics
Funder
National Health and Medical Research Council
Funding Amount
$607,967.00
Summary
Multidrug, antibiotic resistance is a serious global threat. It is a real possibility that in the absence of new antibiotics, common infections could soon become untreatable. This project will develop a novel class of antibiotics that target the core structures of essential bacterial proteins. The successful outcome of this work will also aid the development of specific peptide-based inhibitors for numerous additional diseases, including viral and fungal infections and cancer.
Repurposing Amiloride Into Breast Cancer Drugs With A Dual-Targeting Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$611,966.00
Summary
This project aims to transform a diuretic drug (amiloride) into a breast cancer drug that acts via a novel molecular mechanism. The science of medicinal chemistry will be used to remove amiloride's diuretic effects whilst gaining potent dual-activity against two breast cancer targets, uPA and NHE1. Our study will validate a new pharmacological approach in cancer treatment and produce patented drugs suitable for development into first-in-class breast cancer drugs.
A Novel Mechanism For Therapeutically Modulating Neurotransmitter-activated Ion Channels
Funder
National Health and Medical Research Council
Funding Amount
$667,529.00
Summary
This project aims to elucidate the mechanisms by which macrocyclic lactones bind to brain ion channel receptors. This will reveal fundamental new insights into the operation of these receptors and will have important implications for the design of novel treatments for a variety of central nervous system disorders.
Structural Biology Of Bacterial Lipid II-glycopeptide Antibiotic Interactions
Funder
National Health and Medical Research Council
Funding Amount
$605,190.00
Summary
Drug resistant bacteria are threatening our ability to successfully treat serious life-endangering infections, with many common antibiotics no longer effective. We will study in atomic detail how one class of antibiotics interacts with bacteria in order to design new members of this group that can overcome resistance.
We aim to develop a new class of cholesterol-lowering drugs by blocking the interaction between a protein in the blood called PCSK9 and its receptor, which is implicated in cholesterol absorption. We will do this by designing small stable peptides (mini proteins) that mimic part of the receptor and have the potential to interfere with the normal PCSK9 binding process. These drugs should be less expensive and potentially less immunogenic than competing therapies based on antibodies.
Design And Delivery Of Peptide-based Anti-cancer Grb7 Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$603,126.00
Summary
The Grb7 protein is overproduced in many types of cancer cells and plays a role in cancer cell growth and spread. The current proposal builds upon the discovery of a peptide-based Grb7 inhibitor that has anti-cancer activity. This proposal is to prepare more potent inhibitor molecules that can efficiently reach the target cancer cells. Such molecules will be used for the study of Grb7 and for the development of a new Grb7-based anti-cancer drug therapy.
Development Of Peptide-based Scaffolds For Intracellular Cancer Targets
Funder
National Health and Medical Research Council
Funding Amount
$1,479,836.00
Summary
The overall aim of this project is to develop peptide-based drugs that are able to cross cell membranes and inhibit specific targets inside cells leading to more effective, safer and cost effective drugs for cancer. One potential outcome of the project will be new drug leads to treat melanoma and leukemia that are likely to be less toxic, more potent and less likely to develop resistance than current treatments.
Molecular Epidemiology And High Resolution Surveillance Of Salmonella Enterica Serovar Typhimurium In Australia
Funder
National Health and Medical Research Council
Funding Amount
$583,180.00
Summary
Salmonella typhimurium is a leading cause of the food-borne disease – salmonellosis. It is responsible for considerable morbidity and has an enormous economic cost. Molecular typing is the key to rapidly identify and control outbreaks. This project will employ next generation sequencing technology to develop a new molecular typing scheme. A surveillance system that integrates molecular typing data and epidemiological data will be developed for outbreak investigation and disease prevention.
Epigenetic Determination Of Neuronal Vulnerability And Neurodegenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$617,857.00
Summary
Neurons are faced with diverse forms of stress everyday. Neural diseases exacerbate this stress, causing interference to genes that normally allow neurons to function correctly. As a result, neurons die, and severe loss can result in diseases such as dementia. We have discovered new molecular factors in neurons that insulate their genes from stress, thereby protecting neuron function and health. The proposed research will exploit these mechanisms to better protect neurons from disease.