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.
Pharmacological Targeting Via AKT, PTEN, And TGF-beta Pathway Integration Using Novel Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$634,875.00
Summary
We have identified potentially important interactions of cellular pathways that vary between individual sufferers, but which also provide common molecular targets for novel drug development. Our suite of novel and potent drugs that markedly and selectively inhibit cancer cell growth will be studied to determine if these pharmaceutical agents act to inhibit tumour cell proliferation by targeting common effector molecules of integrated cellular pathways.
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.
Research Fellowship: Understanding G Protein-coupled Receptors (GPCRs)
Funder
National Health and Medical Research Council
Funding Amount
$444,177.00
Summary
This project focuses on drug action at G protein-coupled receptors (GPCRs), the largest class of drug targets. It builds on key discoveries by the applicant that novel sites on GPCRs can be targeted by small molecules in a selective manner, thus minimizing side effects and maximizing therapeutic efficacy. Because this approach can work across most GPCR families, the relevance to the pharmaceutical industry and GPCR-related diseases, such as schizophrenia and diabetes, is very high.
Dementia is the third leading cause of death in Australia and the single greatest cause of disability in the elderly. Current therapies for Alzheimer’s disease (AD), the most common form of dementia, are inadequate and fundamentally new treatment approaches are required. The aim of this proposal is to develop novel drug candidates for the treatment and prevention of AD and other neurodegenerative disorders by targeting a class of cell-surface receptors called G protein-coupled receptors (GPCRs).
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.
G protein-coupled receptors are proteins that exist on every human cell, where they sense, and respond to environmental stimuli. Because of their importance they are targeted by drugs to treat many diseases. However little is known about how drugs activate these receptors and this has hindered new drug development. I use state-of-the-art technology to determine how drugs activate receptors and develop new methods for drug discovery. This work will have major impact on the Pharmaceutical industry
Bitopic Ligands As A Novel Approach To G-protein-coupled Receptor Selectivity
Funder
National Health and Medical Research Council
Funding Amount
$540,356.00
Summary
This project will focus on two important types of brain proteins that have been implicated in various symptoms associated with schizophrenia. The aim is to exploit a new paradigm of drug action that we have discovered, whereby novel compounds can be utilized to simultaneously target multiples sites on these brain proteins, in an effort to discover new mechanisms that can promote more selective signalling and, ultimately, can be used to design safer and more effective medicines.