Using Gene Delivery Technologies To Define Novel Mechanisms Of Skeletal Muscle Adaptation, And Develop Muscle-directed Interventions For Frailty And Serious Illness
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
The focus of my research is to investigate the cellular mechanisms underlying regulation of skeletal muscle size and function in health and disease. By defining these processes we can establish the events contributing to muscle wasting and frailty commonly associated with serious illness and advancing age, and develop interventions to prevent/overcome this important contributor to poor health prospects and reduced survival.
REGULATION OF LIPID METABOLISM IN SKELETAL MUSCLE BY IDOL – A Novel Degrader Of The Very Low Density Lipoprotein Receptor
Funder
National Health and Medical Research Council
Funding Amount
$557,162.00
Summary
More than 1 in 5 Australians are estimated to have increased levels of fats (triglycerides; TGs) in the blood, commonly due to excess dietary intake or genetics. The excess TGs are deposited in skeletal muscle where they can cause insulin resistance, increasing the risk of developing diabetes, the fastest growing chronic condition in Australia. I will examine whether a recently identified protein, IDOL, can reduce accumulation of TGs in skeletal muscle and protect against insulin resistance.
Muscle Thermogenesis In Models Of Predisposition To Obesity
Funder
National Health and Medical Research Council
Funding Amount
$469,289.00
Summary
Obesity is a major health crisis, but effective treatments remain elusive. Body weight is determined by a balance of food intake and energy expenditure. Understanding both sides of this equation is essential to combating obesity. This project will show that the rate at which muscle uses energy is an important determinant of energy balance and contributes to the propensity to become obese. The work will define muscle as a target for developing anti-obesity therapies.
The CDP Ethanolamine Pathway: A New Player In Obesity Induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$652,372.00
Summary
Insulin resistance, a characteristic of type 2 diabetes, is linked to abnormal metabolism of lipid (fat) in tissues such as liver and muscle. This project aims to identify a novel pathway which may promote a build up of lipids in muscle and therefore leads to the development of type 2 diabetes. This work may provide a basis for understanding and optimizing treatment of insulin resistance by regulating the control of fat metabolism in muscle.
An Integrated Approach To Identify The Molecular Mechanisms Contributing To The Pathogenesis Of Insulin Resistance: Targeting The Liver And Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$415,218.00
Summary
The inability of muscle and liver to utilise sugar from the blood is a major problem that contributes to the development of obesity and diabetes. How these problems occur is unknown. The goal of my research is to identify what causes the muscle and liver problem, and whether fixing these problems will reduce obesity and diabetes. Since the number of people with obesity and diabetes is predicted to double over the next decade, we need to understand the cause of these diseases.
The nuclear hormone receptors (NRs) translate hormonal, metabolic & pathophysiological signals into gene regulation, and several NRs are very important in human health. NRs are important therapeutics targets in the treatment of dyslipidemia, insulin insensitivity and breast cancer. Our data identifies new and novel NR targets that can be therapeutically/pharmacologically exploited in the context of exercise capacity, metabolic disease and breast cancer.
Understanding The Metabolic Consequences Of Impaired AMPKa2 And NNOS� In Skeletal Muscle: Implications For The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$575,527.00
Summary
The inability of muscle to utilise sugar from the blood is a major problem that contributes to obesity and Type 2 diabetes. Since the number of people with these diseases will at least double by 2030, we need to find out what causes this problem. We will examine whether two muscle proteins that are impaired in obesity and Type 2 diabetes are also responsible for impaired sugar utilisation. We think that increasing these muscle proteins will fix the _sugar problem�, and remedy these diseases.
Influence Of In Utero Environment On Diaphragm Structure And Function
Funder
National Health and Medical Research Council
Funding Amount
$494,966.00
Summary
The diaphragm is the major muscle involved in breathing. Normal function of the diaphragm is essential to survival. Preterm babies may be exposed to infection and other agents that interfere with diaphragm development and make breathing efforts weaker after birth, potentially leading to respiratory failure. This study will study diaphragms of preterm lambs to determine how fetal exposure to infection and steroids affect fetal diaphragm development, and if adverse effects are prevented by fetal t ....The diaphragm is the major muscle involved in breathing. Normal function of the diaphragm is essential to survival. Preterm babies may be exposed to infection and other agents that interfere with diaphragm development and make breathing efforts weaker after birth, potentially leading to respiratory failure. This study will study diaphragms of preterm lambs to determine how fetal exposure to infection and steroids affect fetal diaphragm development, and if adverse effects are prevented by fetal treatment with blocking agents.Read moreRead less
Preclinical Testing Of 3 Cysteine-related Drugs For Reducing Dystropathology In The Mdx Mouse Model Of Duchenne Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$378,564.00
Summary
Duchenne muscular dystrophy (DMD) is devastating disease that affects young boys. We propose testing 3 cysteine related drugs which show promise in ameliorating the severity of the disease. The drugs are of particular interest because they are relatively inexpensive, can be taken orally, have few side effects and are already approved for human use. These drugs will tested in an animal model of DMD to test their efficacy.
Intrinsic Response Of Airways To Cyclical Dilation And Elongation In Breathing
Funder
National Health and Medical Research Council
Funding Amount
$355,014.00
Summary
Variations in lung pressures during breathing produce cyclical expansion of the airway tubes. These respiratory movements provide one of the most powerful protective mechanisms for the lung. The protective mechanism fails in asthma so that cyclical expansion of the airway tubes can make breathing more difficult. Current belief is that protective and harmful effects of lung expansion occur by either relaxation or contraction of the muscles lining the airway tubes. Findings from this laboratory su ....Variations in lung pressures during breathing produce cyclical expansion of the airway tubes. These respiratory movements provide one of the most powerful protective mechanisms for the lung. The protective mechanism fails in asthma so that cyclical expansion of the airway tubes can make breathing more difficult. Current belief is that protective and harmful effects of lung expansion occur by either relaxation or contraction of the muscles lining the airway tubes. Findings from this laboratory suggest that the above dogma needs reconsideration. The project will utilize a novel model of the lung to enable us to determine the mechanisms producing both the protective effect, and in asthmatics the harmful effects of cyclical lung expansion. Once the part of the lung that 'fails' in this aspect of asthma has been detected then therapeutic strategies can be put in place to reverse the defect.Read moreRead less