Activated Protein C As A Promoter Of Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$391,650.00
Summary
The healing of wounds is a complex process involving a number of stages, including coagulation, inflammation, remodelling and finally development of full strength skin. Impaired wound healing and-or skin ulcers occur in patients with peripheral arterial occlusive disease, deep vein thrombosis, diabetes, pressure sores and burns. Despite intense investigation, the precise mechanisms associated with impaired healing are poorly understood. APC is a serine protease that plays a central role in physi ....The healing of wounds is a complex process involving a number of stages, including coagulation, inflammation, remodelling and finally development of full strength skin. Impaired wound healing and-or skin ulcers occur in patients with peripheral arterial occlusive disease, deep vein thrombosis, diabetes, pressure sores and burns. Despite intense investigation, the precise mechanisms associated with impaired healing are poorly understood. APC is a serine protease that plays a central role in physiological anticoagulation. APC potently activates gelatinase A, an enzyme that plays a prominent role during the remodelling phase of wound healing and angiogenesis. Our preliminary experiments provide very strong evidence that APC accelerates wound healing using both cultured cells and a rat skin wounding model. There are three aims to this study. The first will use cell culture techniques to investigate the mechanisms of action of APC during wound healing. Secondly, we will expand our pilot studies on the effect of APC as a promoter of wound healing in vivo. These studies will examine the exact dosing and timing regime for APC, using a rat wound healing model. In addition, we will test the effect of APC on slow healing wounds, present in diabetic rats. Thirdly, we will determine whether APC is quantitatively or functionally deficient in human wound fluid derived from slow-healing wounds compared to wounds that heal normally. This is the first time that APC has been implicated in wound healing. It is envisaged that this work will ultimately lead to a novel topical treatment of APC to accelerate slow-healing wounds.Read moreRead less
Neuroprotective Functions Of Autophagy Regulators In Alzheimer's Disease
Funder
National Health and Medical Research Council
Funding Amount
$434,644.00
Summary
The accumulation of the beta amyloid protein has a central role in AD and enhancing its removal improves memory loss in animal AD models. This project builds on my recent finding of regulators of a cell housekeeping system, “autophagy” which accelerate removal of beta amyloid in cells. This study will advance knowledge into the protective functions of the autophagy regulators in reducing AD symptoms. Findings from this work might provide the basis for developing effective anti-AD therapeutics.
Inhibition Of AMPK Signalling As A Strategy For Decreasing Appetite
Funder
National Health and Medical Research Council
Funding Amount
$644,266.00
Summary
The enzyme AMP-activated protein kinase (AMPK) has previously been implicated in mediating increased food intake in response to fasting and the appetite-inducing hormone ghrelin. In this study we propose to investigate whether inhibition of AMPK has promise as a strategy to reduce hunger in the context of dietary restriction and increases in energy expenditure, such as exercise. We will also test whether a new AMPK inhibitor has the potential to reduce appetite signalling in cells and in mice.
Alteration Of Glucose Metabolism By GPCR Activation
Funder
National Health and Medical Research Council
Funding Amount
$444,796.00
Summary
In type 2 diabetes the effect of insulin to stimulate glucose transport in fat cells and skeletal muscle is impaired so there is great interest in identifying insulin-independent mechanisms that increase glucose transport. Several G protein-coupled receptors (GPCRs) regulate glucose transport independently of insulin but the mechanisms involved in these effects are largely unknown. This project investigates how GPCRs regulate glucose homeostasis and will evaluate them as potential treatments.
Site-specific Tau Phosphorylation To Treat And Understand Alzheimer’s Disease
Funder
National Health and Medical Research Council
Funding Amount
$943,902.00
Summary
Alzheimer’s disease (AD) is the most common form of dementia. Unfortunately, current therapies are ineffective. Our laboratory has made an important contribution to understanding the events that lead to brain cell malfunction in AD. I recently found a novel concept that changes the view of AD completely. In the next 3 years, I aim to develop therapeutic tools based on this novel concept and find out more about how it can protect brains from AD.
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.
Physiological Effects Of Manipulating AMP-activated Kinase Genes
Funder
National Health and Medical Research Council
Funding Amount
$351,110.00
Summary
The AMP-activated protein kinase is a metabolic stress sensing protein kinase responsible for matching the supply of energy to the body's functions. During vigorous exercise it senses metabolic stress (reduction in energy) caused by muscle contraction and stimulates glucose uptake and burning of fat to provide energy. The AMP-activated protein kinase also regulates the production of nitric oxide that is important in controlling blood pressure and blood clotting. Reduced caloric intake activates ....The AMP-activated protein kinase is a metabolic stress sensing protein kinase responsible for matching the supply of energy to the body's functions. During vigorous exercise it senses metabolic stress (reduction in energy) caused by muscle contraction and stimulates glucose uptake and burning of fat to provide energy. The AMP-activated protein kinase also regulates the production of nitric oxide that is important in controlling blood pressure and blood clotting. Reduced caloric intake activates the AMP-activated protein kinase to suppress energy consuming activities and modify the expression of genes. Many of the conditions that activate the AMP-activated protein kinase (exercise, reduced caloric intake) are associated with a healthy life style, increased longevity and resistance to age onset diseases including cardiovascular disease (atherosclerosis, hypertension), obesity, neurodegeneration and diabetes. By manipulating the gene for the AMP-activated protein kinase in mice we expect to learn more about its key physiological roles and give new insight into the control of age onset diseases.Read moreRead less