The Role Of Androgens In Osteoblast Development And Bone Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
Male hormones are essential for the growth and maintenance of bone in men, but exactly how and when they act on the bone forming cells is unclear. We aim to find out what happens when the target for male hormones (receptor) is removed in the bone forming cells at different stages of their development. This project will increase our understanding of how male hormones regulate bone formation and may assist in the design of new therapies for osteoporosis.
The Effect Of Overexpression And Underexpression Of Beacon In Transgenic Mice
Funder
National Health and Medical Research Council
Funding Amount
$316,540.00
Summary
Overweight and Obesity are very prevalent in our society. Obesity is the cause of many medical problems including type 2 diabetes, high blood pressure, abnormal lipids, sleep apnoea, arthritis and some cancers. The idea that individuals can freely choose whether they eat or not eat is only true in the short term. Recent work has clearly shown that the desire to eat (hunger) and the decision to stop eating (satiety) are determined by the net level of many chemicals (neurotransmitters) in an area ....Overweight and Obesity are very prevalent in our society. Obesity is the cause of many medical problems including type 2 diabetes, high blood pressure, abnormal lipids, sleep apnoea, arthritis and some cancers. The idea that individuals can freely choose whether they eat or not eat is only true in the short term. Recent work has clearly shown that the desire to eat (hunger) and the decision to stop eating (satiety) are determined by the net level of many chemicals (neurotransmitters) in an area of the brain called the hypothalamus. Malfunction in some of these neurotransmitters has been shown to cause severe obesity in both animals and humans. A clear understanding of how the hypothalamus regulates body weight may lead to treatments for both severe obesity and anorexia. This project deals with investigating the role of a new hypothalamic protein in body weight regulation. This protein called beacon was discovered by one of the chief investigators (GC) who has shown that when it is injected in the brain it causes rats to overeat and put on excess weight. The aim of this project is to produce mice in which the amount of beacon is increased in the brain and other mice who do not have beacon and then to study the impact onthe regulation of body weight.Read moreRead less
The Effect Of PKC Epsilon On The Insulin Receptor And Whole Body Glucose Homeostasis.
Funder
National Health and Medical Research Council
Funding Amount
$82,261.00
Summary
Increased fat availability is strongly associated with insulin resistance and type 2 diabetes. Data from this lab has shown animals lacking a particular enzyme (Protein Kinase C epsilon) are able to compensate for this insulin resistance and maintain normal blood glucose levels by elevating insulin availability, with a major site of action being the liver. This project therefore aims to examine the action of PKC epsilon on insulin clearance by the liver.
Distinct Populations Of Arc NPY Neurons Control Different Aspects Of Energy Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$843,340.00
Summary
Obesity is caused by an imbalance of energy intake and energy expenditure both of which are controlled by specific neurons in the brain. While different types of neurons important in these processes have been identified how they are organised and work in fulfilling the different functions is unclear. Here we aim to identify subpopulations of neurons that are responsible for specific tasks that would make them more specific targets for drug intervention with a reduced risk of side effects.
Investigation Of Transgenic Mouse Models Of Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$412,200.00
Summary
Type 2 diabetes is a common condition characterised by high blood glucose, that afflicts 700,000 Australians. It causes blindness, kidney failure and an increased risk of heart attack and stroke. despite intensive study over many years, the reasons for the elevated blood glucose in this condition are not fully understood. Several abnormalities can contribute to the high glucose and different researchers have proposed different defects as the initial cause. It has proven difficult to unravel the ....Type 2 diabetes is a common condition characterised by high blood glucose, that afflicts 700,000 Australians. It causes blindness, kidney failure and an increased risk of heart attack and stroke. despite intensive study over many years, the reasons for the elevated blood glucose in this condition are not fully understood. Several abnormalities can contribute to the high glucose and different researchers have proposed different defects as the initial cause. It has proven difficult to unravel the sequence of events in the evolution of the syndrome because high glucose can cause insulin resistance and a defect in insulin secretion, both of which can lead to high blood glucose. One approach to study the consequences of specific defects is to genetically engineer them. The aims of this project are to: 1. make a mouse with reduced ability to store glucose in muscle. 2. test the metabolic consequences of a defect in the manufacture of glycogen (starch) in muscle. 3. study the effects of combining a defect in glucose storage with one that results in an oversupply of glucose. 4. study the effects on a mouse with a genetic predisposition for failure of beta cells (insulin making cells) of a defect in muscle glucose storage and over production of glucose. A successful completion of this grant will greatly enhance our understanding of how blood glucose is increased in Type 2 diabetes.Read moreRead less
TGF-beta Receptor Type III In Normal And Malignant Liver Growth: Modulation Of TGF-beta Activity
Funder
National Health and Medical Research Council
Funding Amount
$361,527.00
Summary
The transforming growth factor-beta (TGF-beta) family is a group of multifunctional growth factors which regulates a number of important cellular functions, including proliferation, differentiation, and survival. Therefore, the proper functioning of this system is critical for the normal development and maintenance of most tissues. Dysregulation of this system is implicated in many pathological conditions, including cancer. The actions of TGF-beta are mediated by three cell surface proteins, ter ....The transforming growth factor-beta (TGF-beta) family is a group of multifunctional growth factors which regulates a number of important cellular functions, including proliferation, differentiation, and survival. Therefore, the proper functioning of this system is critical for the normal development and maintenance of most tissues. Dysregulation of this system is implicated in many pathological conditions, including cancer. The actions of TGF-beta are mediated by three cell surface proteins, termed the type I, II and III TGF-beta receptors. The type I and II receptors are required for transmitting the TGF-beta signal to the nucleus of the cell. Existing data suggest that the type III receptor is not required in TGF-beta signaling but is required for the regulation of TGF-beta levels at the cell surface. However, the function of this receptor and its role in TGF-beta mediated regulation of cell growth and survival is poorly understood. Our earlier work indicated that the TGF-beta type III receptor is particularly important for limiting TGF-beta activity during normal liver development. The currently proposed research will examine the effects of type III receptor deficiency on liver cells in the adult mouse in order to determine whether alterations in cell growth and survival occur in the absence of this receptor. Becauses TGF-beta is a key regulator of liver growth and altered levels of TGF-beta in liver have been demonstrated to lead to liver cancer in mice, we anticipate that targeting the deletion of the type III gene to liver cells will provide a system in which to study compromised regulation of cell growth. This work is therefore expected to yield information relevant to the role of this receptor in TGF-beta regulated processes in normal and cancerous growth. Because the type III receptor appears to control the level of TGF-beta activity, this work will allow further evaluation of the potential for therapeutic uses for type III receptor-like agents.Read moreRead less