Age-Related Changes In Body Composition And Fuel Metabolism: The Role Of Glucocorticoid Signalling In Osteoblasts
Funder
National Health and Medical Research Council
Funding Amount
$820,528.00
Summary
Our previous studies suggest that age related changes in fat tissue could be due to an increased level of glucocorticoids within bone forming cells (osteoblasts). Mice in which the level of glucocorticoids in osteoblasts is selectively decreased were no different from normal mice at a young age but with ageing were protected against development of obesity and diabetes. This project will examine how bone influences age related changes in fat mass and examine ways in which this might be prevented.
Are Chondrocytes The Target Cells Of Glucocorticoid Therapy In Autoimmune Arthritis?
Funder
National Health and Medical Research Council
Funding Amount
$544,619.00
Summary
Glucocorticoids (GCs) are widely used for their potent anti-inflammatory and immunomodulatory effects due to the effects GCs on immune cells or synovial fibroblasts. Recently, we have made the exciting discovery that arthritis mice with glucocorticoid receptor knock-out in chondrocyte are completely resistant to glucocorticoid treatment. This study will identify the mechanisms underlying these hormonal effects with the aim to find new targets for efficient treatments for arthritis.
The Role Of Endogenous Glucocorticoids In The Pathogenesis Of Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$587,697.00
Summary
Osteoarthritis (OA) is a degenerative joint disease and a leading cause of disability. Recently, we found that the development of experimental OA in mice can be slowed if the effects of the body’s own (=endogenous) glucocorticoids were blocked locally. This project will determine how endogenous glucocorticoids accelerate the development of OA. We will further test whether treatment with drugs that block the actions of endogenous glucocorticoids can slow or prevent the development of OA.
How Does Osteocalcin Reverse Glucocorticoid-Induced Dysmetabolism?
Funder
National Health and Medical Research Council
Funding Amount
$635,038.00
Summary
The benefits of glucocorticoids (GCs) are often compromised by adverse effects such as bone loss, diabetes & obesity. There is now evidence that osteocalcin regulates fuel metabolism. Osteocalcin may therefore be a potential target to prevent the adverse metabolic effects of GC therapy. We aim to determine how osteocalcin regulates energy metabolism in adipose tissue and the liver under conditions of GC excess, and whether and how osteocalcin acts through a G-protein coupled receptor.
Obesity ensues when calorie intake exceeds energy expended. Hitherto, up-regulating energy expenditure is a relatively unexplored avenue. This project will address 3 facets of energy expenditure (fat, muscle and neural control). Understanding how sex and steroids act in concert to regulate energy expenditure will pave the way towards developing novel anti-obesity agents. This work will delineate mechanisms that underpin gender differences in the regulation of body weight.
Viral Infection And TGFbeta Impair Glucocorticoid Activity In Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$617,699.00
Summary
Chronic inflammatory lung diseases like asthma and smokers lung are treated with combinations of anti-inflammatory drugs. Powerful anti-inflammatory types of steroid drugs are used in more severe disease. Even these powerful drugs are sometimes not effective enough. Our work is developing an understanding of how inflammation limits the anti-inflammatory effects of steroids and we are devising ways to overcome this with new drugs. We aim to improve treatment of chronic inflammatory diseases, espe ....Chronic inflammatory lung diseases like asthma and smokers lung are treated with combinations of anti-inflammatory drugs. Powerful anti-inflammatory types of steroid drugs are used in more severe disease. Even these powerful drugs are sometimes not effective enough. Our work is developing an understanding of how inflammation limits the anti-inflammatory effects of steroids and we are devising ways to overcome this with new drugs. We aim to improve treatment of chronic inflammatory diseases, especially those affecting the lung.Read moreRead less
Optimising Lung Surfactant Protein Production In The IUGR Fetus At Risk Of Preterm Delivery
Funder
National Health and Medical Research Council
Funding Amount
$463,853.00
Summary
Pregnant women at risk of preterm labour after 24 weeks gestation are increasingly administered glucocorticoids in Australian hospitals in order to promote fetal lung maturation and a successful transition to extrauterine life. Antenatal glucocorticoid treatment reduces overall neonatal mortality, the risk of respiratory distress syndrome and the need for respiratory support. Babies that are born small may not benefit from this treatment in the same way that average size babies benefit.
Glucocorticoid Resistance In Paediatric Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$394,721.00
Summary
Glucocorticoids are among the most effective drugs used in the treatment of many haematological malignancies, including leukaemia, lymphoma and multiple myeloma. However, the development of tumour cell resistance to these drugs remains a significant problem, and clinically relevant mechanisms of glucocorticoid resistance remain poorly understood. This project aims to define mechanisms of resistance to glucocorticoids and develop new drugs to reverse resistance.
Influence Of In Utero Environment On Diaphragm Structure And Function
Funder
National Health and Medical Research Council
Funding Amount
$494,966.00
Summary
The diaphragm is the major muscle involved in breathing. Normal function of the diaphragm is essential to survival. Preterm babies may be exposed to infection and other agents that interfere with diaphragm development and make breathing efforts weaker after birth, potentially leading to respiratory failure. This study will study diaphragms of preterm lambs to determine how fetal exposure to infection and steroids affect fetal diaphragm development, and if adverse effects are prevented by fetal t ....The diaphragm is the major muscle involved in breathing. Normal function of the diaphragm is essential to survival. Preterm babies may be exposed to infection and other agents that interfere with diaphragm development and make breathing efforts weaker after birth, potentially leading to respiratory failure. This study will study diaphragms of preterm lambs to determine how fetal exposure to infection and steroids affect fetal diaphragm development, and if adverse effects are prevented by fetal treatment with blocking agents.Read moreRead less