Neurotransmitter transporters are very good drug targets because modulation of their activity can lead to up and down regulation of neurotransmitter concentrations and thereby influence signalling pathways in the brain. This can be very useful in treating various neurological disorders and also altering normal brain functions such as learning and memory. In this project we will develop a detailed understanding of how glutamate transporters work and in so doing will be in a better position to des ....Neurotransmitter transporters are very good drug targets because modulation of their activity can lead to up and down regulation of neurotransmitter concentrations and thereby influence signalling pathways in the brain. This can be very useful in treating various neurological disorders and also altering normal brain functions such as learning and memory. In this project we will develop a detailed understanding of how glutamate transporters work and in so doing will be in a better position to design subtype and transporter-specific compounds. These compounds will be very useful in defining the role of glutamate transporter subtypes in normal and pathological states and may be useful in treating neurological disorders such as Alzheimer's disease, schizophrenia, ishaemia following a stroke, and motor neurone disease.Read moreRead less
Role Of Conformational Change In Activation Of The Growth Hormone Receptor
Funder
National Health and Medical Research Council
Funding Amount
$242,545.00
Summary
Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its role as an anabolic agent. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and of course, ageing. This project seeks to find out how growth hormone sends its signal into the target cell through its surface receptor. It is believed that ....Growth hormone is an important hormone therapeutic for treating dwarfism. Recently, many new therapeutic applications for growth hormone have been discovered, particularly in relation to its role as an anabolic agent. These include post surgery recovery, enhanced bone fracture healing, Crohns disease, dilated cardiomyopathy, infertility and of course, ageing. This project seeks to find out how growth hormone sends its signal into the target cell through its surface receptor. It is believed that the primary event in signalling is the ability of the hormone to bring two receptors together (receptor dimerization). However, it may be that the receptor already is dimerized, and the role of the hormone is to induce a specific change in shape of the receptor, which transfers the signal of hormone binding into the cell to initiate signalling to the genome. We have good evidence that a specific shape change is required for activation of an important signalling pathway by growth hormone, and the closely structurally related receptor for erythropoietin is already dimerized before hormone binds. We want to find out exactly how the shape change acts, and whether the receptor is predimerized. This information is vital for designing small orally active mimics of growth hormone which could be of great value as an anabolic supplement for the frail elderly.Read moreRead less
This project will test the proposal that rising follicle-stimulating hormone (FSH) levels in ageing females directly accelerate reproductive failure and bone loss , major public health issues due to delayed childbearing and our rising ageing population. We have developed a unique mouse model with elevated FSH levels that cause premature female infertility. We will now use this model to determine the direct effects of high FSH upon ovarian and uterine function, as well as bone loss with age.
Body Mass Index And Mortality In Aboriginal Australians In Northern Territory: A Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$136,220.00
Summary
The ultimate goal of this study is to define a healthy weight range for Aboriginal people. To fulfil this goal, we will investigate the health implications of body weight and weight change in Aboriginal communities. We will assess the association between body weight (as measured by body mass index) and the risk of death by examining how the death rate changes with body weight. The findings will have important implications for health professionals to provide adequate advice to Aboriginal Australi ....The ultimate goal of this study is to define a healthy weight range for Aboriginal people. To fulfil this goal, we will investigate the health implications of body weight and weight change in Aboriginal communities. We will assess the association between body weight (as measured by body mass index) and the risk of death by examining how the death rate changes with body weight. The findings will have important implications for health professionals to provide adequate advice to Aboriginal Australians, and for Aboriginal people to adopt a healthy life style in relation to body weight. Due to the differences in body shape and physiological and environmental factors between Aborigines and other populations, the optimal body weight obtained from other populations may not be applicable to Aboriginal communities. Do males and females have different optimal body weights? Do old and young people have different optimal body weights? This study will provide evidence for answering various questions like these. Individuals with different characteristics may have different optimal body weight values. Such information is useful for the development and modification of dietary guidelines for Aboriginal Australians. The results on the health impact of weight change are important for guiding weight control programs in Aboriginal communities.Read moreRead less
Novel Approach And Insights Into Muscle Stem Cell Transplantation
Funder
National Health and Medical Research Council
Funding Amount
$642,401.00
Summary
The successful use of stem cell therapy absolutely requires the longterm intergration of the therapeutic cells into the target tissue. This application will adapt a chemotherapy-based strategy to drive the successful incorporation and growth of healthy muscle stem cells into diseased muscle. This study will both enhance our understanding of muscle stem cells and provide proof-of-principle for a universal approach to the uptake of stem cells by a target tissue.
IGF-1 AS A THERAPEUTIC AGENT: HOW DOES IGF-1 AFFECT OXIDATIVE STRESS IN DYSTROPHIC AND AGED SKELETAL MUSCLE?
Funder
National Health and Medical Research Council
Funding Amount
$545,243.00
Summary
Loss of skeletal muscle mass (wasting) and function occurs in many clinical conditions, including muscular dystrophy, neuromuscular and inflammatory disorders, and also normal ageing. A growth factor (IGF-1) is a promising therapeutic as it increases protein synthesis. Muscle wasting (loss of protein) is also associated with increased oxidative stress. The project will evaluate the impact of IGF-1 on oxidative stress using genetically engineered mouse models of muscular dystrophy and ageing.