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.
Transcriptome Landscape Of Brown/beige Adipogenesis In Humans
Funder
National Health and Medical Research Council
Funding Amount
$393,369.00
Summary
There are three kinds of fat in the body: white, brown and beige. While excess white fat results in obesity, brown fat is associated with leanness and lowers blood glucose levels. Recent animal experiments show that under certain conditions, white fat can be transformed into beige fat, leading to benefits such as weight loss. The current project grant involves examination of human fat cells grown in the laboratory and investigation on the genetics of brown and beige fat.
Structural Studies Of Thyroid Peroxidase, An Autoantigen In Autoimmune Thyroid Disease
Funder
National Health and Medical Research Council
Funding Amount
$386,423.00
Summary
This proposal is aimed at determining the three dimensional structure of Thyroid Peroxidase, a protein found in the human thyroid gland that is important in the production of the hormone thyroxine. Thyroxine is involved in controlling the rate of metabolic processes in the body and influencing physical development.
Type 2 diabetes is a health crisis in Australia. In this project, we will investigate the mechanisms whereby high glucose and fat impair pancreatic beta-cell function leading to type 2 diabetes. We will establish how endoplasmic reticulum stress and the protein Id1 are linked with loss of beta-cell gene expression and function. The information gained will further our understanding of the basic mechanisms regulating insulin secretion and provide new therapeutic targets for diabetes treatment.
Reversal Of Diabetes In A Humanised Mouse Using A Clinically Applicable Vector System
Funder
National Health and Medical Research Council
Funding Amount
$842,173.00
Summary
Somatic gene therapy is one of the strategies that is being considered to cure Type I diabetes. Specifically, we wish to engineer liver cells to replace beta cell function. The aim of this project is to design a clinically-applicable protocol for the reversal of diabetes using a recombinant adeno-associated vector that delivers genes to human livers with high efficiency showing long term expression without pathogenicity and immunogenicity following a simple intra-peritoneal injection.
Determing Whether Breast Stem Cells Mediate The Risk Of Developing Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$433,894.00
Summary
Whilst the outcomes for women with breast cancer have improved significantly, the incidence of breast cancer continues to increase. Research needs to focus on prevention now to try to stop the increase. Apart from age, our reproductive behaviour is the largest risk factor for breast cancer. If a woman does not bear children, or has them after 35 years of age, she is at 25-50% increased risk of breast cancer. We would like to determine whether the breast stem cells play a role in this and why.
Hypospadias, is a common defect, in which the urethra opens abnormally along the shaft of the penis not at the tip. It affects 1 in every 125 boys born in Victoria each year. However, the cause(s) of over two-thirds of these cases cannot be explained. Our studies using marsupials show that this process is mediated by a hormone (5alpha-androstanediol), with previously undetermined physiological function. This study will provide novel data on the interactions of the genes and hormones that result ....Hypospadias, is a common defect, in which the urethra opens abnormally along the shaft of the penis not at the tip. It affects 1 in every 125 boys born in Victoria each year. However, the cause(s) of over two-thirds of these cases cannot be explained. Our studies using marsupials show that this process is mediated by a hormone (5alpha-androstanediol), with previously undetermined physiological function. This study will provide novel data on the interactions of the genes and hormones that result in defects of penile development.Read moreRead less
Role Of The Adaptive Unfolded Protein Response In Beta-cell Compensation
Funder
National Health and Medical Research Council
Funding Amount
$581,715.00
Summary
Obesity is a strong risk factor for type 2 diabetes. Obese subjects with “robust” pancreatic beta-cells can sustain a compensatory response. Type 2 diabetes arises in subjects with beta-cells that are “susceptible” to dysfunction and death. We will investigate the role of the adaptive unfolded protein response in beta-cell compensation for obesity-associated insulin resistance. Findings will help explain why some individuals but not others develop type 2 diabetes.
Disorders of sexual development are amongst the most common birth defects in humans. These conditions have profound consequences for the physical and psychological health of affected individuals. The incidence of these disorders is on the rise, and this has been linked to our increased exposure to chemicals in the environment that affect how our hormones function. This project will investigate how these chemicals affect hormonal pathways that control early development.
Monitoring Bone Loss And Response To Therapy Through Bone Material And Structural Composition
Funder
National Health and Medical Research Council
Funding Amount
$696,111.00
Summary
Millions of scripts are filled for treatment of osteoporosis. However, there is no way of knowing if these drugs are right for these individuals, if it improves bone strength or are actually doing harm. Bone density measurement is of limited value. We have developed a new analysis method that measures changes in bone structure that tell us if the treatment is or is not working so alternative treatment can be used. The aim of this study is to test this new method.