Dissecting Rapamycin Sensitive And Insensitive Effects Of MTOR
Funder
National Health and Medical Research Council
Funding Amount
$1,183,241.00
Summary
All cells possess machinery that can sense nutrient availability and trigger cell growth and nutrient storage pathways. However, nutrient oversupply is detrimental to health. Recently, it was shown that drugs that inhibit the nutrient sensors have life extending effects. Our laboratory has discovered a novel mechanism by which these drugs might be mediating these beneficial effects that could change the way we think about the beneficial effects of these drugs and their mode of action
Regulation Of Ca2+/calmodulin Dependent Protein Kinase Kinase-2 By Phosphorylation
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
This project will study the regulation of an enzyme called CaMKK2, which plays a pivotal role in controlling a number of important biological functions including brain development, regulation of appetite, energy metabolism and blood pressure. Understanding how this enzyme is regulated may open new avenues for treating Type 2 diabetes, obesity, and cardiovascular disease.
New Insights Into Mechanisms That Coordinate Kinase Signalling And Molecular Motors In Mitosis: A Novel Role For The Protein Scaffold WD-repeat Protein 62 (WDR62).
Funder
National Health and Medical Research Council
Funding Amount
$529,122.00
Summary
Proteins perform all functions within a cell. Commonly, different proteins are assembled into large complexes to carry out processes, such as cell division, with significant implications for human health. Scaffold proteins facilitate the proper assembly of large complexes but are a poorly understood protein class. We will perform molecular analysis of a newly discovered scaffold, WDR62, to define how it drives cell division and reveal how this can be exploited to develop new anti-cancer drugs.
Molecular Regulation Of The Serine-Threonine Kinase ULK1 In Autophagy
Funder
National Health and Medical Research Council
Funding Amount
$299,431.00
Summary
Autophagy or self eating is a basic cellular process and can have either beneficial or adverse effects in cancer. It is essential to determine the status of autophagy in patients before considering drugs that block autophagy for therapy. A protein called ULK1 is needed for autophagy and may emerge as a pathological marker for autophagy in cancer as well as a potential drug target. This grant proposal will study ULK1 regulation and will lay the scientific foundation for its medical application.
Biochemical And Molecular Dissection Of The Mechanisms Controlling Ribosome Biogenesis By The PI3K/AKT/mTOR/MYC Network
Funder
National Health and Medical Research Council
Funding Amount
$545,180.00
Summary
Ribosome synthesis and function are critical for normal cell growth and division and hence this process is exquisitely regulated. Conversely, de-regulated cell growth can lead to cancer. We have identified new roles for the AKT and SGK families of kinases in controlling this process. This proposal aims to establish the mechanisms by which these enzymes control ribosome synthesis to better understand growth control and to provide insight for targeting these pathways in growth driven cancers.
Dissecting The Role Of Selective Insulin Resistance In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$980,624.00
Summary
Insulin resistance is a clinical condition where insulin, secreted from the pancreas in response to meals, is unable to fulfill its normal function. It is intimately linked to obesity and associated diseases - type 2 diabetes, cancer and cardiovascular disease. This proposal examines mechanisms contributing to insulin resistance and how insulin resistance leads to disease. We will identify drug targets with improved specificity and lead to novel insight into the risks of current treatments.
Dissecting The Role Of Insulin-regulated Phosphorylation Of Rab Guanine Nucleotide Exchange Factors In GLUT4 Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$628,459.00
Summary
Diabetes and obesity are epidemic in the developed world. Impaired insulin action is a major cause. A key contributor is reduced glucose uptake into muscle and fat driving the pancreas to overproduce insulin. We have recently discovered three new molecules that we believe hold the secret to how insulin regulates the removal of the glucose from the blood stream after a meal. This proposal focuses on these three molecules and their regulation.
An AMPK Myristoyl Switch Controls AMP Mediated Metabolic Stress Signaling
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
This project is investigating an enzyme called AMP-activated protein kinase that plays a pivotal role in controlling how our bodies regulate energy metabolism in response to exercise and diet. Improved understanding of how this enzyme is regulated may provide new therapeutic methods for mimicking the beneficial effects of diet and exercise to treat multiple metabolic diseases including obesity, Type 2 diabetes and cardiovascular disease.
The Regulation Of Pleiotropic Responses By Bidentate Motifs Embedded In The Fibroblast Growth Factor Receptors
Funder
National Health and Medical Research Council
Funding Amount
$489,336.00
Summary
Cells in our bodies are able to accomplish an impressive array of functions. Diffusible factors (called growth factors) are important in regulating diverse cellular functions. We have identified a new molecular switch inside cells that acts as a master controller of cellular functions. This molecular switch relays information to instruct specific cellular functions. We have shown that these molecular switches are short-circuited in breast cancer promoting cell growth and survival.
Skeletal Muscle Signal Transduction Related To Exercise, Metabolic Disease And Human Health
Funder
National Health and Medical Research Council
Funding Amount
$557,298.00
Summary
Exercise is one of the best prevention and treatment strategies for all major human diseases. Despite these well documented advantages, we still do not know exactly how exercise produces these benefits at the molecular level. A comprehensive understanding of this will lead to new avenues to treat many diseases. This project will monitor thousands of molecular changes that occur in human muscle biopsies following exercise and create the world’s first molecular blueprint of exercise.