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Targeted Development Of AMPK Β2-isoform Allosteric Activators
Funder
National Health and Medical Research Council
Funding Amount
$898,147.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to dramatic increases in the incidence of diseases associated with metabolic dysregulation e.g. type 2 diabetes. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as a cellular fuel gauge. We have discovered a new drug that crucially activates the form of AMPK found in metabolically active organs. We aim to develop this drug to unlock new therapeutic opportunity.
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.
Metabolic Stress Sensing By AMPK: Implications For Energy Balance And Isoform-targetting Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$632,188.00
Summary
Metabolic diseases such as obesity, type 2 diabetes and cardiovascular disease impose enormous medical and economic burdens on Western societies. Our research is focussed on the enzyme AMP-activated protein kinase (AMPK) which acts as the fuel gauge of the cell and is a promising drug target for combating metabolic diseases. Our discoveries provide critical insight on how AMPK is switched on by both energy demand and drugs, and will greatly assist development of AMPK-targetted therapeutics.
Cytokine Signalling And Insulin Resistance In Obesity.
Funder
National Health and Medical Research Council
Funding Amount
$512,065.00
Summary
Western communities are experiencing an epidemic of obesity that is contributing to diabetes, heart disease, and premature death. This project is investigating why being overweight and obese causes diabetes. Improved understanding about how hormones regulates the body's storage and breakdown of fat and responsiveness to insulin will enable the development of new medicines for the treatment of obesity and the prevention of diabetes.
Understanding The Function And Regulation Of G Protein-coupled Receptor Signalosomes And Their Role As High Resolution Signalling Platforms
Funder
National Health and Medical Research Council
Funding Amount
$566,588.00
Summary
G protein-coupled receptors are specialised proteins located on the surface of cells. They are the targets of 50% of currently available pharmaceuticals, but these drugs are derived from limited knowledge of only a fraction of proteins. This proposal will examine exciting and novel properties of receptors that only occur following the assembly of the proteins into specialised networks within cells. The new information will expand our current knowledge, and facilitate future targeted drug design.
Signalosomes And Compartmentalisation In Cellular Homeostasis And Disease
Funder
National Health and Medical Research Council
Funding Amount
$473,646.00
Summary
G protein-coupled receptors are specialised proteins on the surface of cells. They are the targets of 30% of currently available pharmaceuticals. This proposal will examine exciting and novel properties of these proteins that only occur following their assembly into specialised networks in cells. The use of cutting-edge technology will allow us to understand the role of these networks in many diseases. The new information will expand our current knowledge, and facilitate targeted drug design.
An Integrated Systems Biology Approach For The Development Of New Therapeutic Strategies For The Treatment Of High Grade Glioma
Funder
National Health and Medical Research Council
Funding Amount
$696,404.00
Summary
Glioma, the most common adult brain cancer, is incurable. Recent advances now allow us to grow glioma cells directly from patients in the laboratory in a way that preserves the features of the original tumor. In this proposal we will systematically analyze such cells using state-of-the-art technologies to identify new processes important to glioma, which in turn should facilitate the identification of innovative therapeutic approaches.
Targeting Necroptosis Signalling To Counter Stroke-induced Brain Injury
Funder
National Health and Medical Research Council
Funding Amount
$605,809.00
Summary
The origins of the brain injury that arises from stroke remain a matter of enormous interest. Our work suggests that a poorly understood form of cell death, termed necroptosis, contributes to injury to the brain following stroke. In addition to developing an advanced understanding of this process, we will use drugs developed at the Walter and Eliza Hall Institute to test whether blocking this process might be a plausible therapeutic strategy in stroke patients.
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.
Directed Molecular Evolution Of G Protein-coupled Receptors For Stable And Functional Expression In Escherichia Coli
Funder
National Health and Medical Research Council
Funding Amount
$383,479.00
Summary
Approximately half of all prescription drugs on the market act on G protein coupled receptors (GPCRs). The mechanisms underlying GPCR function are mainly unknown due to a lack of structural information. No solved structures exist for any of the estimated 800 human GPCRs, making it difficult to design new drugs. By applying advanced protein engineering techniques I aim to produce human GPCRs in bacteria to ultimately acquire structural information, which will enable novel drug development.