The Regulation Of Insulin Action In Liver And Skeletal Muscle By Protein Kinase C Epsilon
Funder
National Health and Medical Research Council
Funding Amount
$647,604.00
Summary
We have identified an enzyme, protein kinase C epsilon, which has a major negative impact on the control of blood glucose levels. We will now examine the mechansisms by which it affects insulin action in liver and muscle, two major target tissues of the hormone responsible for glucose disposal. This work is expected to validate PKCepsilon or its downstream effectors as therapeutic targets in the treatment of the insulin resistance which accompanies obesity and Type 2 diabetes.
The Role Of Liver Fructose-1,6-phosphatase (FBPase) In Body Weight Regulation
Funder
National Health and Medical Research Council
Funding Amount
$494,718.00
Summary
We have shown that fructose-1,6-bisphosphatase (FBPase), an enzyme important in producing sugar from the liver and one that is connected to Type 2 diabetes, does not cause an increase in sugar production when there is more of the enzyme in mouse livers. It does, however, lower both body weight and the amount of food the mice consume. We therefore hypothesise that liver FBPase is important in controlling body weight in humans and our project aims to find out exactly how and why this happens.
I am a scientist with a background in molecular and cellular pathology. My research relates to studies of animals models of diabetic kidney and heart disease focusing on the discovery of novel treatments.
Reversal Of Diabetes In Pigs Using Liver-directed Gene Therapy
Funder
National Health and Medical Research Council
Funding Amount
$573,807.00
Summary
Type I diabetes mellitus is caused by the autoimmune destruction of the beta cells of the pancreas that secrete insulin. We have shown that we can cure diabetes in spontaneously diabetic mice by delivery of the insulin gene to the liver using a non-pathogenic viral delivery system. The study aims to repeat this work in pigs which have similar physiology to humans. If successful this would be proof-of-principle that we could theoretically control blood glucose levels in humans.
Mineralocorticoid Receptor Co-regulator Recruitment Determines Ligand Specific Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$491,530.00
Summary
Heart disease is a major cause of death and economic burden in Australia and throughout the world. The steroid hormone aldosterone controls salt and water balance,blood pressure and hasa significant role in heart failure. Although drugs that block the aldosterone receptor significantly help patients with heart failure, their use is limited by side effects. This work will identify the profile of proteins that promote aldosterone effects and enable the development of heart-specific blockers.
Characterisation Of The Molecular Mechanisms Mediating Aldosterone-induced Epithelial Electrolyte Transport
Funder
National Health and Medical Research Council
Funding Amount
$488,386.00
Summary
The steroid hormone aldosterone regulates blood pressure by controlling sodium retention. The importance of this role is underlined by the fact that all known mongenetic hypertensive conditions involve aldosterone or sodium retention. Aldosterone mediates this effect by activating an intracellular receptor protein that in turn switches on specific genes. This study seeks to identify the genes that are switched on (or off) by aldosterone and to characterise the region of the gene that interacts w ....The steroid hormone aldosterone regulates blood pressure by controlling sodium retention. The importance of this role is underlined by the fact that all known mongenetic hypertensive conditions involve aldosterone or sodium retention. Aldosterone mediates this effect by activating an intracellular receptor protein that in turn switches on specific genes. This study seeks to identify the genes that are switched on (or off) by aldosterone and to characterise the region of the gene that interacts with the receptor. Both cell and gene specific factors are thought to be important in defining the nature of this interaction; these factors will also be sought. This information will enhance our understanding of the basic biology of sodium transport in the colon and the kidney which in turn will clarify the role of aldosterone in high blood pressure, cardiac disease and perhaps even stress.Read moreRead less
Novel Actions Of Leptin In Implantation And Placental Function
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
The establishment, growth and function of the placenta is of critical importance to the successful maintenance and completion of pregnancy. The placenta is effectively the lifeline of the growing fetus through its supply of nutrients, removal of wastes and coordination of hormone signals that regulate fetal growth and development. Among these signals the hormone leptin, which is produced primarily by fat cells and regulates food intake, has been identified as a crucial player in the control of f ....The establishment, growth and function of the placenta is of critical importance to the successful maintenance and completion of pregnancy. The placenta is effectively the lifeline of the growing fetus through its supply of nutrients, removal of wastes and coordination of hormone signals that regulate fetal growth and development. Among these signals the hormone leptin, which is produced primarily by fat cells and regulates food intake, has been identified as a crucial player in the control of fetal growth. In human pregnancy, the placenta becomes an additional major source of leptin, and this is secreted into the mother and the fetus. Recent work in animal models also indicates that the process of implantation, whereby the embryo embeds itself in the lining of the uterus and establishes a placenta, cannot proceed in the absence of leptin. But how leptin exerts these critical effects on the implantation process and placental function is not known. In this study we will explore several potential actions of leptin in the uterus and placenta, and examine whether the leptin signaling system is aberrant in cases where the fetus does not grow normally. Of particular interest is the possible interaction of leptin with another group of important signaling molecules called the peroxisome proliferator-activated receptors, or PPARs. One of these, PPAR-gamma, plays an indispensable role in the establishment of the placenta, particularly in relation to the formation of blood vessels, a process that is also a target for leptin action. Several lines of evidence, most notably in fat cells, suggest that both PPAR-gamma and leptin regulate common aspects of cell function. Such interactions provide us with important clues as to how leptin and the PPARs could work together to promote the optimal establishment, growth and function of the placenta, and these will be explored in this project.Read moreRead less
Characterisation Of Alterations In The Androgen Signalling Axis That Contribute To Treatment Failure In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$559,157.00
Summary
Prostate cancer is a major health problem in Western Countries including Australia, where it is the most common newly diagnosed invasive cancer and the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis of prostate cancer, many men are still diagnosed with disease that already has or will spread to other sites such as bone (ie metastatic disease). For those men with metastatic disease, reduction in testicular androgens by surgical or medical mean ....Prostate cancer is a major health problem in Western Countries including Australia, where it is the most common newly diagnosed invasive cancer and the second leading cause of cancer deaths in men. Although there have been improvements in the diagnosis of prostate cancer, many men are still diagnosed with disease that already has or will spread to other sites such as bone (ie metastatic disease). For those men with metastatic disease, reduction in testicular androgens by surgical or medical means (ie androgen ablation) is the only effective treatment option available. While androgen ablation is initially effective, treatment failure is common, resulting in a very poor overall survival rate. Evidence from our studies and others suggest that, the androgen receptor, which mediates the growth regulatory effects of androgens is often defective in prostate tumour cells. These altered or mutant receptors are activated inappropriately by other sex hormones such as estradiol and even agents used in the treatment of prostate cancer whereas the normal receptor is activated only by testicular androgens. This mechanism may explain why treatment fails in a subset of men with advanced prostate cancer. The major objective of our current studies is to define how these mutant androgen receptors cause treatment failure and facilitate prostate tumour growth. In addition, the current studies will evaluate a novel approach to treatment of prostate cancer which, based upon our preliminary results, has the potential to be effective even if alterations are present in the androgen receptor. The current studies therefore will provide a better understanding of factors controlling the growth of prostate tumours, and develop improved treatment approaches for advanced prostate cancer.Read moreRead less
This study is investigating an autoimmune disease called lymphocytic hypophysitis, involving the master gland in the body, the pituitary. It often affects pregnant women and is under diagnosed. The aim of our study is to determine the cause of this disease and its unexplained link with pregnancy. We are also working on a new diagnostic test which will enable doctors to confirm the diagnosis by serological means. At present, invasive pituitary biopsy is needed. Whilst developing this new test, we ....This study is investigating an autoimmune disease called lymphocytic hypophysitis, involving the master gland in the body, the pituitary. It often affects pregnant women and is under diagnosed. The aim of our study is to determine the cause of this disease and its unexplained link with pregnancy. We are also working on a new diagnostic test which will enable doctors to confirm the diagnosis by serological means. At present, invasive pituitary biopsy is needed. Whilst developing this new test, we have identified three proteins and their genes. This information may have major implications for the study of pituitary gland function.Read moreRead less