Regulation Of Skeletal Muscle AMP-activated Protein Kinase By Glycogen
Funder
National Health and Medical Research Council
Funding Amount
$561,558.00
Summary
The enzyme AMP protein kinase has three parts (subunits) and is central to controlling the body's metabolism. We have discovered that one subunit is essential for tightly associating the enzyme with muscle glycogen which is a source of high energy and efficient metabolism. We will identify where the enzyme attaches to glycogen, and how diet and exercise alter this association. Understanding this could lead to new approaches for treating Type 2 diabetes where energy metabolism is disrupted.
The Putative Drug Metabolising Enzyme SULT4A1 Is A Sulfotransferase Inhibitor
Funder
National Health and Medical Research Council
Funding Amount
$467,851.00
Summary
The sulfotransferase SULT4A1 is a novel protein found predominantly in neurons but its function is unknown. This project will investigate the mechanisms that the body uses to regulate the levels of this protein and how it may interfere with other enzymes essential for metabolising hormones and neurotransmitters.
Structure And Function Of The AMPK Glycogen-binding Domain
Funder
National Health and Medical Research Council
Funding Amount
$538,764.00
Summary
The AMP-activated protein kinase (AMPK) is an enzyme responsible for coordinating metabolism in response to energy supply (diet) and energy demand (exercise). Research into this kinase can increase our understanding of how diet and exercise are so important for maintaining health. The kinase acts either by sensing when cellular energy levels become too low for normal functioning or when the body tells it by sending a chemical messenger (hormone) that overall energy levels are low. This results i ....The AMP-activated protein kinase (AMPK) is an enzyme responsible for coordinating metabolism in response to energy supply (diet) and energy demand (exercise). Research into this kinase can increase our understanding of how diet and exercise are so important for maintaining health. The kinase acts either by sensing when cellular energy levels become too low for normal functioning or when the body tells it by sending a chemical messenger (hormone) that overall energy levels are low. This results in activation of energy-producing pathways and inhibition of energy-consuming pathways, allowing cells to match supply with demand to ensure their survival. The AMPK comprises of three proteins that together form a functional enzyme. I have previously found that AMPK localizes to a source of cellular energy called glycogen (sugar stores) via one part that I have called the glycogen-binding domain. In this application I aim to obtain a thorough understanding of the molecular basis of how the glycogen-binding domain affects AMPK function in muscle and heart following exercise. In addition this research may lead to the identification of new molecules, similar to glycogen, that are important for AMPK regulation and may lead to the development of a new class of drugs for Type 2 Diabetes. Research into AMPK promises to dramatically increase our knowledge of how to reduce the risk of cardiovascular and neurodegenerative diseases, diabetes and obesity and provide an understanding of the reasons these diseases develop.Read moreRead less
Adipose Triglyceride Lipase: Regulation And Implications For The Aetiology Of Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$323,453.00
Summary
Obese individuals have elevated fat levels in the blood and muscle, which contributes to the development of other diseases such as type 2 diabetes. A newly discovered protein named adipose triglyceride lipase (ATGL) is essential for fat breakdown. This project aims to identify how ATGL operates and determine whether defective ATGL function leads to type 2 diabetes. These studies will assist in the development of strategies aimed at reducing fatty acids in blood and muscle.
The Role Of Dietary Protein On Weight Loss And Body Composition In Men And Women With Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$208,055.00
Summary
Obesity is an increasing problem in the community and is associated with an increased incidence of high blood pressure, high cholesterol and triglycerides, diabetes, heart disease and cancer. Although conventional dietary advice for weight loss is a low fat high carbohydrate and high fibre diet there is a very strong interest in the media and the general population in alternative diets that feature reduced carbohydrate with the remainder of the diet either protein or a mixture of protein and fat ....Obesity is an increasing problem in the community and is associated with an increased incidence of high blood pressure, high cholesterol and triglycerides, diabetes, heart disease and cancer. Although conventional dietary advice for weight loss is a low fat high carbohydrate and high fibre diet there is a very strong interest in the media and the general population in alternative diets that feature reduced carbohydrate with the remainder of the diet either protein or a mixture of protein and fat. Unfortunately there is very little published data to guide the decisions of health professionals in this area and there is a strong demand for such information. We plan to perform 2 large weight loss studies which focus on high protein diets with one exchanging protein for carbohydrate and keeping fat constant and the second exchanging protein for fat keeping carbohydrate constant. We will assess whether the high protein diets blunt the decrease in metabolic rate that occurs with weight loss, and whether it spares some of the inevitable loss of muscle mass. We will also measure whether high protein diets improve glucose metabolism in people already at risk of diabetes and heart disease because of their obesity and high insulin levels.Read moreRead less
Understanding And Controlling PAS Domain Interactions In Basic Helix-loop-helix Transcription Factors
Funder
National Health and Medical Research Council
Funding Amount
$599,918.00
Summary
We want to understand how particular proteins control the activity of genes that are a crucial part of the body's ability to respond to environmental stresses, such as low oxygen, seizure and environmental pollutants. The knowledge gained will help decipher the events that result in correct function in the cell, and the misregulation that leads to toxic outcomes and disease states. We will search for new compounds with potential application as therapeutics for cancer, heart disease and stroke.
Protein Networks Mediating Copper Balance And Their Break-down In Disease.
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Neurological disorders (eg. Alzheimer s, Parkinson s and prion diseases) impose a growing health burden on society. Exciting new therapeutic possibilities stem from the discovery that copper (Cu) plays a central role in the disease process. Our research will help foster a holistic understanding of the protein network regulating copper balance, particularly in the brain, and where it breaks down in disease. Clinical benefits include new targets for diagnosis and treatment of Cu-related diseases.
Understanding The Importance Of Lipid Metabolism In Mediating The Anti-diabetic Effects Of Metformin
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
Obesity is a major cause of adult onset Type 2 diabetes. This project is investigating the mechanism of action of the glucose lowering drug metformin on fat metabolism. We are investigating whether the regulation of two enzymes, involve in fat synthesis and the burning of fat respectively that are important for metformin�s action. Through this research we hope to improve on the treatment of Type 2 diabetes and cardiovascular disease.
Regulation Of Protein Kinases And Their Substrates
Funder
National Health and Medical Research Council
Funding Amount
$553,197.00
Summary
Our research is concerned with the control of the body's energy metabolism via an enzyme called AMPK. This enzyme is at the hub of metabolic control in response to diet and exercise. AMPK controls energy expenditure in response to demand as well as appetite. It is well recognized that diet and sedentary life-styles are major contributors to obesity and cardiovascular disease. We are testing how a new drug activates AMPKand how energy expenditure can be increased.
Mosiquite bourne viruses like dengue fever and West Nile virus are responsible for many deaths each year, with little prophylatic treatments available. We want to look at how these viruses can replicate in cells and hide from our immune system. We have found that cholesterol plays a major role in efficient virus replication and is crucial for us to fight infections. Our studies have indicated that West Nile virus can alter cholesterol metabolism and concentration within our bodies.