Role Of Sphingolipid Signalling In Hepatic Insulin Resistance And Its Application In Prediction Of Risk For Type 2 Diabetes And Prediabetes
Funder
National Health and Medical Research Council
Funding Amount
$563,305.00
Summary
Type 2 diabetes is expected to reach epidemic proportions in the coming decades. Prediabetes is usually unrecognized and constitutes a major public health concern that needs earlier interventions, because the majority of prediabetic subjects proceed to T2D. We have identified an enzyme that plays an important role in insulin signalling. The possibility is that the level or activity of this enzyme is a potential biomarker of the prediabetes state and could be also used as a target
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.
Do Synaptic-like Mechanisms Control Insulin Secretion?
Funder
National Health and Medical Research Council
Funding Amount
$593,235.00
Summary
An estimated 415 million people world-wide were diagnosed with diabetes in 2015. One of the causal factors in disease is the dysregulation of insulin secretion. We have developed new techniques to study insulin secretion that has led us to propose a new model for secretory control. This proposal sets out experiments to critically test this model. The outcomes could have wide-reaching impact on understanding and for future treatment and prevention of the diabetes.
Characterisation Of Autophagy Deficiency In Skeletal Muscle Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$956,237.00
Summary
Defects in skeletal muscle are a cause of muscle disease, and also have broad health implications for diabetes, obesity and liver disease. As such, it is important to understand the processes required for healthy muscle and how signals communicate from muscle to the liver and fat, which integrate whole body metabolism. This application examines how the cellular degradation process known as autophagy integrates these important processes by investigating a novel gene regulator of this pathway.
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
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.
Control Of The Ras/Erk Signaling Pathway By The Brahma Chromatin-remodeling Complex
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
Hormones bind and initiate molecular signals within cells to proliferate or change into specific cell types. This is important for growth and development of different tissues. A pathway which is critical for transmitting the effects of hormones in cells is the Ras pathway. New studies by the applicants indicate that the Brahma complex, a molecule important in controlling the levels of proteins in cells, activates the Ras pathway. This project will define how Brahma controls the Ras pathway.
Only recently has it emerged that our cells have a built-in backup mechanism that instructs cells to die in extreme cases, such as when viruses have hijacked a cell. A misfiring backup mechanism is thought to underlie a number of human diseases, including inflammatory disease. Our investigation will establish a starting point for the development of novel anti-inflammatory drugs.
Characterising The Novel Signalling Mechanism For A New Interferon
Funder
National Health and Medical Research Council
Funding Amount
$525,485.00
Summary
We have discovered a new regulatory protein called interferon epsilon, made in the female reproductive tract and is crucial for protection against bacterial( Chlamydia) and viral (Herpes Simplex Virus) infections. However, we are yet to understand how it interacts with target cells. This grant will study how IFN? binds to cells and the nature of the signals it transmits. This will help us understand its role in disease and its clinical potential
SETD7-dependent Regulation Of Hippo/YAP And Wnt/beta-catenin Pathways In The Intestine
Funder
National Health and Medical Research Council
Funding Amount
$601,950.00
Summary
Colon cancer accounts for approximately 10% of all cancer-related deaths in Australia. One of the most common causes of colon cancer is a mutation in a signalling pathway called the Wnt/beta-catenin pathway. Despite this knowledge, there are currently no drugs that directly target this pathway to treat colon cancer. We have now identified a new way to control this pathway and have developed a potent and specific drug to block activation of this pathway.