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The Differential Innervation Of Fat - Potential To Target Visceral Adiposity
Funder
National Health and Medical Research Council
Funding Amount
$486,818.00
Summary
Levels of abdominal fat are closely correlated with metabolic syndrome. We propose experiments to identify unique characteristics (neurotransmitters or receptors) of neurons deep in the brain that project specifically to this type of fat or other less harmful subcutaneous fat. We can then test the functional significance of these unique elements in animal experimets involving gene knockdown or pharmacological approaches to modify their function and test the effect on fat distribution
In men, oestrogen may be important for strong bones and maintaining a healthy weight. Men with prostate cancer are given medical castration treatment to decrease testosterone, because testosterone is required for prostate cancer growth. Because oestrogen is derived from testosterone, they also have very low oestrogen levels. We want to conduct a trial in these men to find out whether giving back oestrogen will prevent bone loss and weight gain, among other health benefits.
Unravelling The Mechanisms By Which Insulin Hypersecretion Is Detrimental To ß-cell Function And Survival In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$727,758.00
Summary
Type 2 diabetes is associated with reduced levels of the hormone insulin that results in an increase in blood sugar. Evidence suggests that when the cells that make insulin are overworked they fail to produce the right amount of this hormone to keep blood sugar levels normal. In this proposal we will determine how overworking the insulin producing cells damages them and assess whether reducing the need to overwork is beneficial and thus lead to reduced blood sugar levels in Type 2 diabetes.
Novel Metabolic Actions Of HDL With Potential Therapeutic Implications For Type 2 Diabetes And The Metabolic Syndrome.
Funder
National Health and Medical Research Council
Funding Amount
$349,683.00
Summary
There are currently in excess of 170 million patients diagnosed with type 2 (late onset) diabetes in the world and this figure is expected to double by 2030. Almost one in four Australians 25 years and over has either diabetes or a condition of impaired glucose metabolism. These conditions pose significant problems in terms of both individual suffering and economic burden. Poor diet, sedentary lifestyles with resultant weight gain and increased obesity rates underlie the escalating prevalence of ....There are currently in excess of 170 million patients diagnosed with type 2 (late onset) diabetes in the world and this figure is expected to double by 2030. Almost one in four Australians 25 years and over has either diabetes or a condition of impaired glucose metabolism. These conditions pose significant problems in terms of both individual suffering and economic burden. Poor diet, sedentary lifestyles with resultant weight gain and increased obesity rates underlie the escalating prevalence of type 2 diabetes. Our proposal investigates a novel approach to treat these conditions. We have identified an important link between HDL (good) cholesterol and glucose and fat metabolism in human muscle cells. We have shown that HDL increases glucose uptake into muscle cells. This process would be expected to remove glucose from blood vessels where it causes damage which ultimately contributes to heart attack and stroke. Furthermore, we have shown that HDL increases the amount of fat the body uses. HDL may therefore not only remove damaging fat from blood vessels, but also help to reduce body weight. Our study seeks to determine the relevance of these mechanisms in both healthy individuals and patients with type 2 diabetes. At the conclusion of this grant we expect to understand whether HDL raising strategies may be a an effective new therapy for type 2 diabetes. Specifically, we will understand: 1. how HDL exerts its beneficial effects and 2. whether acute and chronic HDL elevation using drugs improves glucose and fat metabolism in humans.Read moreRead less
Novel Interplay Of Oestrogen And Growth Hormone In Regulating Lipid Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$673,045.00
Summary
These studies provide insights into the mechanisms and role of oestrogen in regulating whole body and liver fat metabolism. Oestrogen-related medications that modify the action or tissue availability of oestrogen are widely used therapeutics and can predispose to obesity and fat accumulation in the liver. Whether the effect is direct or through interplay with other metabolic hormones is unknown. This proposal examines their metabolic consequences and impact on obesity and liver health.
Genomic And Non-genomic Actions Of Androgens In Regulation Of Fat Mass And Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$395,421.00
Summary
Men have lower amounts of body fat than women, but are more likely to deposit fat around the stomach and abdominal region than women. This increased abdominal fat in men significantly increases the risk of developing type 2 diabetes and heart disease. The differences between men and women suggest that there is hormonal control of fat development; however, little is known regarding how male sex hormones, androgens, control these processes. We will investigate how androgens control fat formation, ....Men have lower amounts of body fat than women, but are more likely to deposit fat around the stomach and abdominal region than women. This increased abdominal fat in men significantly increases the risk of developing type 2 diabetes and heart disease. The differences between men and women suggest that there is hormonal control of fat development; however, little is known regarding how male sex hormones, androgens, control these processes. We will investigate how androgens control fat formation, and the response of fat and muscle tissue to glucose and insulin, using mutant mouse strains. These mouse strains have a mutation in the androgen receptor, a protein which acts as a key-lock mechanism to allow tissues to respond to androgens. This mutation stops the androgen receptor from functioning, so these mice can be used to determine the function of androgens acting through the androgen receptor. We will study three strains of mutant mice: (i) in which the androgen receptor is non-functional in all tissues of the body; (ii) in which the androgen receptor is non-functional only in fat tissue, but normal in all other tissues; and (iii) in which the androgen receptor is non-functional only in skeletal muscle, but is normal in all other tissues. The aim of our research is to determine the effect of the mutations in these three different mouse lines on paramateres including the amount of fat formed, the site of fat deposition, the levels of lipids and insulin in the blood and their response to glucose. The androgen receptor is a master switch that turns on or off other genes. Therefore, we also aim to identify which genes are controlled by the androgen receptor in fat and muscle. This research will identify how androgens control fat development and function, and will identify genes that mediate these actions in fat and muscle. This will provide potential molecules that could be used therapeutically to treat obesity and prevent type 2 diabetes and heart disease.Read moreRead less
Dietary Fats As Drivers Of Obesity-related Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$336,767.00
Summary
Obesity leads to diabetes and heart disease but not all body fat seems to be bad. Increased fat around the waist (especially the visceral fat around the intestine and internal organs) is particularly bad. Visceral fat secretes a lot of inflammatory molecules. This research aims to understand how visceral fat becomes inflamed and how we might use diet and other methods to reduce both the amount of visceral fat and its level of inflammation; thus reducing both obesity and its health consequences.
Transforming Mealtime Insulin Dosing Using An Innovative New Bolusing Calculator To Optimise Glycaemic Control In Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
People with type 1 diabetes require life-long insulin injections to maintain their blood glucose levels in the optimal range. Mealtime dose estimations based solely on carbohydrate have limited efficacy as they fail to take fat and protein into account. The aim of this project is to develop an evidence-based insulin bolusing calculator integrated into a smartphone app to enhance blood glucose control and reduce the daily burden of disease and the risk of life-threatening complications.