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GLUCOCORTICOID EFFECTS ON BONE: THE ROLE OF THE OSTEOBLAST
Funder
National Health and Medical Research Council
Funding Amount
$464,520.00
Summary
Glucocorticoids (usually referred to as cortisone) are used as therapeutic agents in almost all fields of medicine, where they have been proven to be of great benefit to countless patients suffering from diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and malignancies. Glucocorticoids are also of live saving benefit to patients who have undergone organ transplantation. It is, however, well known that glucocorticoids may also exert deleterious effects on bone, muscle, ca ....Glucocorticoids (usually referred to as cortisone) are used as therapeutic agents in almost all fields of medicine, where they have been proven to be of great benefit to countless patients suffering from diseases such as rheumatoid arthritis, asthma, inflammatory bowel disease and malignancies. Glucocorticoids are also of live saving benefit to patients who have undergone organ transplantation. It is, however, well known that glucocorticoids may also exert deleterious effects on bone, muscle, cartilage and skin, causing osteoporosis, muscle wasting and skin damage. As a matter of fact, cortisone-induced muscle and bone disease is one of the most frequent and serious side effects associated with glucocorticoid treatment, and substantially affects quality of life and co-morbidity in many patients. In the present project, we aim to develop new strategies for the understanding and prevention of costisone-induced bone disease. The first step is to investigate the mechanisms of actions of glucocorticoids in bone. To this aim, we have generated a model in which a cortisone- inactivating enzyme is produced in excess in the bone forming cells (osteoblasts). Previous studies have shown that these cells are protected against the effects on cortisone, while other cells not producing this enzyme remained vulnerable. We now intend to use this model to study the mechanisms of glucocorticoid action on bone and muscle under normal and diseased conditions (e.g. in a model of glucocorticoid excess and in a model of rheumatoid arthritis). We also intend to study how internal glucocorticoids affect the development of bone forming cells. Our long-term aim is to uncover new ways to target drug action to the desired tissues and cells, while protecting other tissues and cells from deleterious side effects.Read moreRead less
The Role Of Circadian Rhythm Genes In The Regulation Of Energy Balance And Substrate Metabolism In Muscle And Liver
Funder
National Health and Medical Research Council
Funding Amount
$349,263.00
Summary
Obesity is increasing at an alarming rate worldwide and as the standard of living increases in developing countries such as India and China, the incidence of obesity and its related diseases of diabetes, cardiovascular disease and cancer will become the major health problem of the 21st century. The epidemic of obesity appears to be due to a complex interaction between genetic background and changes in the environment such as reduced physical activity and increased availability and consumption of ....Obesity is increasing at an alarming rate worldwide and as the standard of living increases in developing countries such as India and China, the incidence of obesity and its related diseases of diabetes, cardiovascular disease and cancer will become the major health problem of the 21st century. The epidemic of obesity appears to be due to a complex interaction between genetic background and changes in the environment such as reduced physical activity and increased availability and consumption of high energy food. The accumulation of excess body fat in most individuals is not a precipitous event that occurs over a few days or weeks. Obesity actually occurs insidiously over a period years and is essentially the cumulative result of small differences in daily energy balance. In humans and animals energy balance is subject to diurnal or day-night variations in body temperature, feeding behaviour and physical activity (sleep-wake cycles). Recent research has determined that all tissues in the body have the same genes that regulate circadian (daily) rhythms in the brain. It has also become clear that the expression of these gene cycles over 24 hours in muscle liver and fat tissue the same way that they do in the brain. What is not understood is the extent to which these circadian genes control energy metabolism pathways such as glucose and fat utilisation and storage in liver and muscle. The aim of this grant is to test the effects of changing diet, feeding times and circulating hormones on metabolism and gene expression in muscle and liver to determine the extent to which circadian rhythm genes regulate the normal diurnal metabolism of glucose and fat and whether dysregulation of these systems contributes to metabolic disease.Read moreRead less
Determinants Of Brown Adipose Tissue Activation - Implication For The Regulation Of Energy Balance And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$617,192.00
Summary
One of the most important recent findings in the biology of obesity has been the revelation that brown adipose tissue (BAT) is present and functional in adult humans. Even more important, the amount of BAT seems to be related to the extent of obesity. The challenge now is to harness the means by which BAT is activated. Understanding the central neural control pathways and the rate limiting steps in the BAT itself will pave the way for new anti-obesity strategies.
Improving Successful Long-term Weight Loss By Deactivating The Human Famine Reaction
Funder
National Health and Medical Research Council
Funding Amount
$799,102.00
Summary
There are more than 7 million overweight or obese adults in Australia. With conventional methods of weight loss, only 5% of these people will be able to achieve permanent weight reduction of any significance to health outcomes. This project aims to develop more effective and permanent methods of weight management through comparing effectiveness of continuous versus intermittent dieting; and determining what metabolic, hormonal and behavioural factors predict weight regain.
I am a reproductive biologist whose research is focussed around understanding how the early events of conception and embryo development are controlled. Critical aspects of my research are to determine the consequences to pregnancy and adult health if the
Charting The Interface Between Cellular Metabolic States And Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$653,196.00
Summary
The research successes of Molecular Biology and Biochemistry have given us detailed pictures of the regulatory and metabolic states of cells and tissues, yet we know little about how these states affect each other. We hypothesise the existence of regulatory interactions between ribonucleic acids, enzymes and metabolites to connect gene expression and metabolism. We will employ novel RNA Biology methods to discover such regulatory interactions in medically important cellular contexts.
Carnitine Acetyltransferase (CrAT) Regulates Appetite And Body Weight Through The Melanocortin System
Funder
National Health and Medical Research Council
Funding Amount
$547,087.00
Summary
Carnitine metabolism in peripheral tissues, such as muscle, maintains appropriate cellular metabolism and function. Little is known about carnitine metabolism in specific populations of brain cells regulate food intake and appetite. This project aims to understand how carnitine metabolism affect brain cells that regulate food intake and body weight.