Impact Of Advanced Glycation On Anti-atherogenic Properties Of High Density Lipoprotein
Funder
National Health and Medical Research Council
Funding Amount
$372,471.00
Summary
Type 2 diabetes is a rapidly growing medical problem in Australia and around the world. Diabetes affects human health through its complications and the cardiovascular complications are a cause for major concern. One of the complications is the effect on plasma lipids: it makes cholesterol carrying particles to accumulate in the blood vessels, causing atherosclerosis. We intend to investigate how diabetes modify these particles making them atherogenic.
Sphingosine Kinase: A Target For Obesity-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$626,845.00
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 liver 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 liver.
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.
Many heart diseases are associated with impairment of energetics of the heart. Improving the heart's energetics can lead to improved survival and long-term outcomes. Perhexiline is a heart medication that works by improving the way the heart uses energy. Although effective, it is associated with long-term toxicities. Better understanding of this medication may lead to less adverse effects and also provide a basis for further investigation of drug development in the future.
Functional Effects Of Polymorphic Variation Of The Aromatase (CYP19) Gene On Enzyme Activity:relationship To Disease
Funder
National Health and Medical Research Council
Funding Amount
$237,708.00
Summary
After menopause, oestrogen synthesis changes from an ovarian to an adipose source by concersion of androgens to estrogens, a process catalyzed by aromatase, the product of the CYP19 gene. We will generate mutants of the CYP19 gene that we have previously found in humans by site-directed mutagenesis and observe the effects of these mutants on aromatase function. This research will help with diagnosis and treatment of breast and other cancers and osteoporosis in humans .
Are Oligodendrocytes The Missing Link In Amyotrophic Lateral Sclerosis Pathogenesis?
Funder
National Health and Medical Research Council
Funding Amount
$1,054,405.00
Summary
Amyotrophic Lateral Sclerosis (ALS) is a debilitating and progressive neurodegenerative disease. Recent research suggests important cells of the central nervous system called glia play a role in disease onset and progression. We are interested in a type of glia called oligodendrocytes; they are crucial for supporting the survival of the cells that die in ALS. Only through understanding the underlying biology of ALS can we aim to identify effective therapies that will benefit patients.
Signaling Pathways To Enhance Potency Of AMPK-targeting Drugs
Funder
National Health and Medical Research Council
Funding Amount
$661,966.00
Summary
Sedentary lifestyles and consumption of high energy foods has led to epidemics of obesity-related metabolic diseases that place enormous financial and medical burden on the Australian economy. An attractive drug target to treat these diseases is AMP-activated protein kinase (AMPK) which functions as both a cellular fuel gauge and co-ordinator of whole-body metabolism. Our goal is to improve AMPK drug potency by identifying novel processes that sensitize AMPK to drugs.
The Role Of The AMPK-ACC2 Signaling Axis In Metabolic Control During Exercise And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$540,973.00
Summary
Australian society is experiencing an epidemic of obesity that is contributing to diabetes, cardiovascular disease and premature death. This project is investigating how exercise might prevent obesity and type 2 diabetes by examining the major pathways that regulate fat metabolism.
This research proposal will identify changes in liver-secreted proteins during the development of fatty liver, and in the transition from fatty liver to the more advanced form of liver disease, non-alcoholic steatohepatitis (NASH). Understanding the differences in protein secretion between NASH patients and patients with normal/fatty liver will provide the opportunity to identify disease biomarkers that could be determined from a blood sample. This will provide a major shift in clinical care.
Regulation Of Ca2+/calmodulin Dependent Protein Kinase Kinase-2 By Phosphorylation
Funder
National Health and Medical Research Council
Funding Amount
$570,334.00
Summary
This project will study the regulation of an enzyme called CaMKK2, which plays a pivotal role in controlling a number of important biological functions including brain development, regulation of appetite, energy metabolism and blood pressure. Understanding how this enzyme is regulated may open new avenues for treating Type 2 diabetes, obesity, and cardiovascular disease.