Neuropathic pain is particularly difficult to treat and existing medications have considerable side effects. This project will develop a new set of glycine transport inhibitors that have the potential to provide pain relief without side effects.
Resolving And Targeting The Complex Molecular Mechanisms Underlying GPCR Signalling
Funder
National Health and Medical Research Council
Funding Amount
$1,071,370.00
Summary
Receptors are located on the surface of all human cells to allow our cells to respond to their environment. Over 30% of prescription drugs act through particular receptors called GPCRs, however effective drugs without side effects are difficult to develop because we do not have a deep understanding of how GPCRs transmit complex signals. In this proposal we seek to resolve the atomic-level details of GPCR signalling to assist in the development of better drugs for a diverse range of diseases.
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.
UGT Enzymes In Chemotherapeutic Drug Metabolism: New Avenues To Improve Drug Response And Overcome Resistance
Funder
National Health and Medical Research Council
Funding Amount
$610,005.00
Summary
Tumours treated by chemotherapy often become resistant to the drugs, leading to relapse and reduced chance of survival. We will study one of the main pathways leading to drug resistance, which could lead to the development of new ways to overcome resistance and improve cancer treatment outcomes.
Pharmacological Targeting Of Integrated Oncogenic And Tumour Suppressive Pathways Using Novel Therapeutics.
Funder
National Health and Medical Research Council
Funding Amount
$510,953.00
Summary
We will investigate NDRG1, a novel molecular target that has been demonstrated to inhibit the progression of numerous cancers. We aim to better understand the underlying function of NDRG1 in pancreatic cancer and how we can potentially target this gene with novel therapeutics being developed in our lab. We hope that this new approach will lead to promising treatments and a better outcome for those suffering from pancreatic cancer.
A Novel Metabolic Role For UDP Glycosyltransferase 8 (UGT8)
Funder
National Health and Medical Research Council
Funding Amount
$419,144.00
Summary
The UDP glycosyltransferases (UGTs) are a family of enzymes that remove drugs and toxins from the human body as well as control levels of naturally produced molecules such as bile acids and hormones. We found that a new member of this family called UGT8 processes bile acids in the kidney and intestine and can affect how bile acids act to regulate metabolism. Our studies uncover new roles for bile acids in liver, kidney and gut health and in metabolic disorders such as diabetes and obesity.
Allosteric Modulation And Biased Signalling At The Calcium-sensing Receptor
Funder
National Health and Medical Research Council
Funding Amount
$636,242.00
Summary
The calcium-sensing receptor is a major target for the treatment of endocrine and bone disorders. However, the development of drugs for this receptor is challenging due to limited understanding of potential sites of drug interaction and how individual drugs may differentially change signalling from the receptor. This project will address these critical knowledge gaps, which may allow for improved therapeutic outcomes.
Rational Co-targeting Of G Protein-coupled Receptors As A Novel Approach Towards Treating Neuropsychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$620,399.00
Summary
Schizophrenia is a common mental disorder with multiple symptoms. Current therapeutics only treat some of these symptoms. This project will focus on two important brain proteins implicated in schizophrenia. With the hypothesis that the rational targeting of these two proteins will lead to the design of more effective medicines for treatment of schizophrenia we will develop novel methods to selectively and simultaneously and target these two proteins.
A New Therapeutic Target For Stress-related Relapse
Funder
National Health and Medical Research Council
Funding Amount
$685,266.00
Summary
Relapse and hazardous drinking represent the most difficult clinical problems in treating patients with alcohol use disorders. We have identified a novel system in the brain for the regulation of stress-induced relapse. Successful completion of this project will indicate improved pharmacotherapeutic strategies for the treatment of alcoholism and drug abuse. Given the scale and costs of substance abuse disorders, improved therapeutic approaches will have immediate and sustained impact.
Novel Treatments Of Fibrosis For Hypertensive Heart Disease
Funder
National Health and Medical Research Council
Funding Amount
$912,536.00
Summary
A recognised risk factor for cardiovascular disease is high blood pressure which contributes to a stiffer heart that can ultimately lead to heart failure. There are very few treatments that can reduce heart stiffening, called fibrosis. This project is focused on the preclinical testing of novel compounds that we have developed to reverse the build-up of fibrosis in the heart, which will lead to better treatment of elderly patients with high blood pressure and poorly-functioning hearts.