Epilepsy is one of the most common chronic neurological disorders; it affects 1% of the world’s population, yet about 1 in 3 patients fail to achieve seizure control with current drugs. We will improve the properties of small molecules (drugs) that specifically target the GTPase activity of the enzyme dynamin, to reduce seizure effect in the brain by a novel mechanism. We will optimize and pre-clinically test these future chemical entities as potential anti-epileptic drugs.
Structure-based Design Of Novel Therapeutics For Multi-drug Resistant Neisseria Gonorrhoeae
Funder
National Health and Medical Research Council
Funding Amount
$669,148.00
Summary
Multiple drug resistance (MDR) in bacteria represents one of the most intractable problems facing modern medicine. The recent superbug, MDR-Neisseria gonorrhoeae (MDR-Ng), causes the sexually transmitted infection gonorrhoeae. A multi disciplinary team with expertise in structural biology, medicinal chemistry and bacteriology will establish a comprehensive knowledge base aimed at developing new antibiotics to treat MDR-Ng by targeting a bacterial protein virulence factor.
Development Of Small Molecule Modulators Of Apoptosis
Funder
National Health and Medical Research Council
Funding Amount
$621,558.00
Summary
Cancers rely on the deregulation of key cellular pathways. Along with biological and genetic tools, small molecules are powerful probes to understand these mechanisms. During the course of this research program, we will develop new and drug-like molecules that reinstate the cell death process to combat malignancies. This research will bring important advances for potential chemotherapies and create probes to better understand the biology of programmed cell death processes.
Unraveling Fibrosis By Pharmacological Targeting Of The G Protein-coupled Receptor, RXFP1
Funder
National Health and Medical Research Council
Funding Amount
$798,618.00
Summary
Peptides, with their high specificity and low toxicity profiles, are highly attractive alternatives to small molecule drugs. H2 relaxin, a peptide hormone, has a strong potential for treating fibrosis. However, the large size of H2 relaxin makes it difficult and expensive to manufacture. Once administered to patients, it is also quickly degraded. We have developed a small anti-fibrotic relaxin peptide, and propose to understand its mechanism of action and improve its therapeutic indices.
Modulation Of Feeding Through Pharmacological Targeting Of The Relaxin-3 Receptor RXFP3
Funder
National Health and Medical Research Council
Funding Amount
$584,955.00
Summary
Relaxin-3 is a neuropeptide that regulates a number of physiological processes, including food intake, suggesting that the relaxin-3 receptor RXFP3 may be a new target for treatment of eating disorders such as obesity. This project will develop new selective and high-affinity ligands for RXFP3, which will be critical pharmacological tools for the preclinical studies and evaluation of this system.
Antibiotic resistance is a looming public health crisis. New antibiotics with new mechanisms of action are desperately needed. The long-term goal of this research is to develop new drugs that disarm bacteria to overcome the problem of antibiotic resistance.
DYRK1A As A Novel Target For Glioblastoma Therapies
Funder
National Health and Medical Research Council
Funding Amount
$620,294.00
Summary
Glioblastoma is a form of brain cancer that is currently incurable. We have discovered that switching-off an enzyme called DYRK1A (using ‘DYRK1A inhibitors’) kills glioblastoma cells. This therapeutic advantage is even greater when combined with drugs approved for other cancers. This project will develop new DYRK1A inhibitors and examine a novel combination treatment for glioblastoma patients. This could initiate a novel therapy that could significantly extend patients’ lives.
Malaria is a major global health problem. The protein AMA1 plays a key role in the invasion of host cells by malaria parasites, and agents that inhibit this interaction prevent host cell invasion and thus represent leads for the development of anti-malarial drugs. We have identified a number of chemical scaffolds that target a key site on AMA1. In this project we will optimize these leads to generate potent ligands for this site and evaluate the efficacy of these ligands as anti-malarial agents.
Structural Studies On The Immune Effector Perforin: Developing Mechanism-based Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$1,116,594.00
Summary
Perforin is an essential weapon deployed by the human immune cells in order to destroy virally infected or cancerous cells. Despite this key role, unwanted or excessive perforin function can result in disease and can severely impact on successful treatment of leukaemia through bone marrow transplantation. This application aims to understand the molecular details of perforin function, and to apply this knowledge to develop perforin inhibitors.
Many of the most serious diseases of Western societies including obesity, Type 2 diabetes, cancer growth and metastasis and cardiovascular disease have metabolic dimensions. The enzyme AMPK regulates cellular and whole body energy homeostasis by coordinating metabolic pathways to balance energy demand with nutrient supply. We are studying the structure and function of AMPK with the aim of better treating metabolic diseases.