Identifying A Novel Role For Pigment Epithelium-derived Factor In Obesity-related Metabolic Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$361,637.00
Summary
Obesity is an important factor contributing to insulin resistance and type 2 diabetes; however, the factors linking these disorders are not well defined. A protein called PEDF is elevated in obesity and type 2 diabetes. This project will examine how PEDF causes insulin resistance and whether blocking PEDF's actions prevents insulin resistance. Successful completion of this project may lead to therapeutics that reduce the risk of developing type 2 diabetes.
Role Of FoxO Proteins In The Regulation Of Skeletal Muscle Anabolism, Catabolism And Insulin Sensitivity
Funder
National Health and Medical Research Council
Funding Amount
$503,426.00
Summary
Loss of muscle tissue or muscle wasting is a hallmark of many common health problems including diabetes, cancer, Cushing's syndrome, sepsis, HIV-Aids and renal failure. In the past 2-3 years important progress has been made in understanding the molecular regulation of both catabolism (muscle wasting) and anabolism (muscle growth) within mammalian skeletal muscles. It has been known for some time that a certain family of transcription factors, known as FoxO proteins, activate catabolic pathways. ....Loss of muscle tissue or muscle wasting is a hallmark of many common health problems including diabetes, cancer, Cushing's syndrome, sepsis, HIV-Aids and renal failure. In the past 2-3 years important progress has been made in understanding the molecular regulation of both catabolism (muscle wasting) and anabolism (muscle growth) within mammalian skeletal muscles. It has been known for some time that a certain family of transcription factors, known as FoxO proteins, activate catabolic pathways. However, recently, we have shown that FoxO proteins also cause muscle wasting by blocking anabolic pathways. Our new data heighten the importance of targeting FoxO proteins are therapeutics for human diseases where muscle tissue wasting occurs. This proposal will investigate methods that will allow for blocking the action of FoxO proteins in the hope that muscle wasting can be prevented.Read moreRead less
The Role Of Protein Kinase C Epsilon In The Generation Of Lipid-Induced Insulin Resistance In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$474,750.00
Summary
Insulin normally reduces blood sugar levels by increasing glucose uptake and storage in certain tissues, especially muscle. Type 2 diabetes is characterized by a failure of these tissues to respond adequately to insulin. This loss of sensitivity to the hormone is known as insulin resistance, and has been strongly linked to increases in the availability of fat, although the reasons for this are not clear. Certain fat molecules are able to cause the activation of pathways within cells which can in ....Insulin normally reduces blood sugar levels by increasing glucose uptake and storage in certain tissues, especially muscle. Type 2 diabetes is characterized by a failure of these tissues to respond adequately to insulin. This loss of sensitivity to the hormone is known as insulin resistance, and has been strongly linked to increases in the availability of fat, although the reasons for this are not clear. Certain fat molecules are able to cause the activation of pathways within cells which can interfere with the normal signalling of insulin. We have recently found that mice lacking an enzyme thought to be involved in such negative pathways are less susceptible to insulin resistance caused by high-fat feeding. The aim of this project is to investigate the mechanism by which this enzyme contributes to inhibition of insulin action. We will determine the step in normal insulin signalling which is blocked by the activation of the enzyme upon increased fat supply. This will help us to determine the pathway leading from the enzyme to insulin signalling. We will also identify the particular form of fat which leads to activation of the enzyme. This work will lead to a better understanding of the mechanisms by which fats can play a role in the generation of insulin resistance, so that they can be targeted both for the development of new and more effective treatments for the disorder and for prevention of its onset.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775746
Funder
Australian Research Council
Funding Amount
$102,000.00
Summary
GC/MS facility for medical, bioanalytical and environmental research. The research will contribute to the bioremediation of heavily polluted sites in Sydney and the knowledge gained and the technology developed will be applicable to sites all over the world. Fundamental knowledge in Systems Biology will have applications to advance Australian export industries based on fermentation. Advances in chemical ecology and biotechnology will impact in areas such as contact lenses, implants, therapeutics ....GC/MS facility for medical, bioanalytical and environmental research. The research will contribute to the bioremediation of heavily polluted sites in Sydney and the knowledge gained and the technology developed will be applicable to sites all over the world. Fundamental knowledge in Systems Biology will have applications to advance Australian export industries based on fermentation. Advances in chemical ecology and biotechnology will impact in areas such as contact lenses, implants, therapeutics and water treatment. Probing pituitary hormone action will lead to greater understanding of health issues such as abnormal body composition, obesity and diabetes.Read moreRead less
Discovery and development of novel insulin sensitising compounds for the treatment of Type 2 diabetes. Diabetes is one of the major health problems facing Australia today, and current treatments are proving inadequate to combat this disease. We previously discovered a new drug with potential for development for the treatment of diabetes. In this project, we will identify how this drug works to combat diabetes in cell and animal models, and use novel chemistry approaches to modify the drug to imp ....Discovery and development of novel insulin sensitising compounds for the treatment of Type 2 diabetes. Diabetes is one of the major health problems facing Australia today, and current treatments are proving inadequate to combat this disease. We previously discovered a new drug with potential for development for the treatment of diabetes. In this project, we will identify how this drug works to combat diabetes in cell and animal models, and use novel chemistry approaches to modify the drug to improve its properties and reduce potential side-effects. The outcomes of this project will be understanding of a new biological process that contributes to the development of diabetes, and the discovery and characterisation of new chemical compounds that could be developed as drugs to treat diabetes.Read moreRead less
Genome wide screening for gene products that regulate the celluar dynamics of lipid droplets. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also provide novel ta ....Genome wide screening for gene products that regulate the celluar dynamics of lipid droplets. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also provide novel targets and strategies for treating obesity. The proposed study will also benefit Australian agriculture by providing strategies to improve oil production from plant seeds. Read moreRead less
Use of a cell based assay to identify novel insulin-sensitising agents. Diabetes and obesity are currently escalating to epidemic proportions in Australia and there is an urgent need to develop new therapeutics. A major feature of these disorders is impaired insulin action. We have recently developed and validated an exciting new assay for insulin action in fat cells. In this project we propose an exciting research program encompassing major research and biotechnology groups in Australia to u ....Use of a cell based assay to identify novel insulin-sensitising agents. Diabetes and obesity are currently escalating to epidemic proportions in Australia and there is an urgent need to develop new therapeutics. A major feature of these disorders is impaired insulin action. We have recently developed and validated an exciting new assay for insulin action in fat cells. In this project we propose an exciting research program encompassing major research and biotechnology groups in Australia to utilise this technology to identify novel insulin-sensitising agents. These agents will be used for drug discovery purposes by our industry partner ChemGenex and as novel tools to dissect the mechanism of insulin action.Read moreRead less
The cellular dynamics of lipid droplets: implications for obesity and biodiesel production. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also identify novel com ....The cellular dynamics of lipid droplets: implications for obesity and biodiesel production. Obesity is a pandemic that if not stopped, will lead to huge social and economic problems in Australia. In essence, the hallmark of human obesity is the accumulation of cellular lipid droplets. This research will benefit Australia by providing a fundamental understanding of how lipid droplets are formed. This will have immediate international impact at the scientific level and will also identify novel compounds and strategies for treating obesity. The proposed study will also benefit Australian agriculture and energy industry by providing strategies to improve the production of plant oil and biodiesel. Read moreRead less
Characterisation of the novel mitochondrial protein (CABC1/ADCK3) and its role in protecting against oxidative stress. This is the first detailed characterisation and mechanistic study on a protein that protects against oxidative stress and neurodegeneration. Demonstrating the basis for this oxidative stress and its possible contribution to the cellular phenotype will be of benefit in understanding the disease process and ultimately designing approaches to minimise oxidative stress. An investiga ....Characterisation of the novel mitochondrial protein (CABC1/ADCK3) and its role in protecting against oxidative stress. This is the first detailed characterisation and mechanistic study on a protein that protects against oxidative stress and neurodegeneration. Demonstrating the basis for this oxidative stress and its possible contribution to the cellular phenotype will be of benefit in understanding the disease process and ultimately designing approaches to minimise oxidative stress. An investigation of this protein presents an opportunity for the investigator to work at the forefront in this field adding to Australia's scientific leadership in the area. It also represents an ideal project for post-graduate training and is a collaboration between groups in Brisbane and Melbourne. Read moreRead less