Effects Of Replacement And Withdrawal Of Testosterone In Human Males On Muscle, Bone And Fat
Funder
National Health and Medical Research Council
Funding Amount
$156,682.00
Summary
Male sex hormone or androgen deficiency (AD) is a common, but under-diagnosed condition. AD decreases well being and contributes to muscle weakness, bone fragility and weight gain. Cutting edge technology will be used to help explain how AD may relate to these negative effects, particularly on muscle function. Given the importance of aging, frailty, osteoporosis and obesity, understanding the role of hormones in these conditions may have major implications for prevention and treatment.
Determining Fundamental Mechanisms Compromised In Kir-linked Disease States
Funder
National Health and Medical Research Council
Funding Amount
$600,040.00
Summary
The human nervous system and organs are reliant on precisely controlled transmission of electrical currents through sodium and potassium channels. Their core functions are compromised when currents fail to switch on and off normally. Faulty potassium channels are implicated in diabetes, epilepsy and heart failure. This project re-examines the mechanisms controlling potassium channels, with a view to scientific and therapeutic discrimination between the different classes present in human cells.
A Novel Lipid Sensitive Kinase And Its Role In Obesity-induced Inflammation And Insulin Resistance.
Funder
National Health and Medical Research Council
Funding Amount
$560,045.00
Summary
It is now apparent that obesity leads to chronic low grade inflammation which results in insulin resistance or pre-diabetes. The mechanisms that link obesity-induced inflammation to insulin resistance are not well understood, but involve lipid oversupply. We have preliminary data identifying that a protein, not known to previously play a role in metabolic diseases, is a critical mediator of lipid-induced inflammation. We will investigate the clinical potential of blocking this protein.
Reducing the fat burden: Identification of novel cellular and molecular targets for alleviating skeletal muscle insulin resistance. Insulin resistance and the associated consequences are a major public health problem in Australia and cost the healthcare system >$1.1 billion/year. Exercise training and thiaziolidinedione (TZD) treatment are therapies that partially ameliorate insulin resistance through distinct and independent mechanisms. However, neither intervention represents a viable long-ter ....Reducing the fat burden: Identification of novel cellular and molecular targets for alleviating skeletal muscle insulin resistance. Insulin resistance and the associated consequences are a major public health problem in Australia and cost the healthcare system >$1.1 billion/year. Exercise training and thiaziolidinedione (TZD) treatment are therapies that partially ameliorate insulin resistance through distinct and independent mechanisms. However, neither intervention represents a viable long-term strategy: exercise training has low compliance, while chronic TZD use is associated with several adverse side effects (edema, weight gain etc.). We will investigate the metabolic, cellular and molecular mechanisms by which these therapies each exert their positive effect on insulin action with the aim of identifying novel targets for future drug interventions. Read moreRead less
Programming of appetite and bodyweight by the interaction of maternal diet and angiotensin during peri-natal life. The project describes a phenotype for appetite and body weight that can be altered by maternal dietary omega-3 PUFA (environmental factors), at a critical period during peri-natal life (developmental phase) and that the effect on body weight is opposite when endogenous angiotensin is increased (hormonal factor). The project aims to discover how these different factors interact to p ....Programming of appetite and bodyweight by the interaction of maternal diet and angiotensin during peri-natal life. The project describes a phenotype for appetite and body weight that can be altered by maternal dietary omega-3 PUFA (environmental factors), at a critical period during peri-natal life (developmental phase) and that the effect on body weight is opposite when endogenous angiotensin is increased (hormonal factor). The project aims to discover how these different factors interact to produce the phenotype by defining the critical period and systematically identifying genes that are expressed during this period. The effect of manipulating maternal dietary omega-3 PUFA and the role of angiotensin will then be examined. The project will discover how genetic, hormonal and environmental factors interact during the perinatal period of life to program food intake and body weight in adult life. Read moreRead less
Exploring The Therapeutic Potential Of TRAIL In Diabetes And The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$446,374.00
Summary
TNF-related apoptosis-inducing ligand (TRAIL) is a protein with potentially useful actions in human health and disease. TRAIL is able to prevent atherosclerosis, the cause of heart attacks and strokes. In addition, we have recently shown that its actions on fat and the pancreas may prevent the development of the metabolic syndrome and type 2 diabetes. These studies will explore the therapeutic potential of TRAIL for the prevention of diabetes and heart disease in a range of animal models.
Enzymatic synthesis, microencapsulation and biological evaluation of a new class of omega-3 derived functional food ingredients. Inflammatory mediated diseases such as cardiovascular disease, type-2 diabetes, metabolic syndrome and Alzheimer's disease are major causes of death in Australia. Rates of these diseases are rising over time, partly due to poor diet including low consumption levels of healthy omega-3 fatty acids from fish. This project aims to develop healthy food ingredients from natu ....Enzymatic synthesis, microencapsulation and biological evaluation of a new class of omega-3 derived functional food ingredients. Inflammatory mediated diseases such as cardiovascular disease, type-2 diabetes, metabolic syndrome and Alzheimer's disease are major causes of death in Australia. Rates of these diseases are rising over time, partly due to poor diet including low consumption levels of healthy omega-3 fatty acids from fish. This project aims to develop healthy food ingredients from naturally occurring omega-3 fatty acid derivatives that are more stable to oxidation and more biologically active than fish derived omega-3 fatty acids. The development of these omega-3 derivatives as functional food ingredients could provide an additional strategy for helping to prevent the rapid increase in inflammatory mediated diseases in the Australian population.Read moreRead less
The Role Of Myo18b In Myopathies And Sarcomere Assembly
Funder
National Health and Medical Research Council
Funding Amount
$860,776.00
Summary
Muscle force is provided by a specific structure within the muscle cell termed the sarcomere. Sarcomeres are the engine-room of muscle cells, that act as complex cellular machines to controls muscle contraction. Many muscle degenerative disorders are caused by defects within the sarcomeres, but how this occurs is not well understood. This grant examines how one such muscle waiting disease, or myopathy, results from mutations in a gene encoding a component of the sarcomere called Myo18b.
We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.