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
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
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.
A Prospective Study Of The Effects Of Early Life Growth On Adult Mammographic Density
Funder
National Health and Medical Research Council
Funding Amount
$460,517.00
Summary
It is now well-known that a woman's breast density, as measured by a breast scan, is a predictor of her future risk of breast cancer. It is also known that women who are heavier as babies and grow rapidly before age 7 are more likely to develop breast cancer in adult life. The effects were strongest in women who had early puberty. It has been suggested that there are critical points in early life growth that contribute to higher breast density in middle-age. Population-based surveys with early l ....It is now well-known that a woman's breast density, as measured by a breast scan, is a predictor of her future risk of breast cancer. It is also known that women who are heavier as babies and grow rapidly before age 7 are more likely to develop breast cancer in adult life. The effects were strongest in women who had early puberty. It has been suggested that there are critical points in early life growth that contribute to higher breast density in middle-age. Population-based surveys with early life growth data on large numbers of women that span birth to adulthood are necessary to estimate accurately the association between early life growth and breast density in middle age. Few such studies exist; Tasmanian Asthma Study is one of them. In 1968, all 4,194 female Tasmanian school children born in 1961 were surveyed and height and weight measured. Subsequently, weight and height measurements were carried out on samples of this cohort. We are currently conducting the 37-year follow-up of the TAS and to date have traced 87% and achieved a response rate of 77% (2,850) for a postal survey. This included self-reported weight and height measurements and detailed information reproductive history and the use of hormones. Weight, height and waist to hip ratio are currently measured on 600 of these respondents. We have access to school medical records of the full cohort, which have weight and height data measured at school medical inspections throughout school years, and maternal records so far for half of the total cohort, which have information on birth weight and length, and period of gestation. Hence, TAS now provides an ideal opportunity, unique within Australia, to investigate prospectively the association between early life growth and mammographic density in middle-age women. We will measure breast density in these women now they are in their late 40s, using the Australian Mammographic Density Research Facility at The University of Melbourne.Read moreRead less
DNA Damage Induced By UVA And UVB In Squamous Cell Carcinoma Progression
Funder
National Health and Medical Research Council
Funding Amount
$65,000.00
Summary
Australia has the highest incidence of skin cancer in the world. This results from immigration of individuals with fair skin to Australia. Skin cancer is three times as common as all other cancers combined. Overall, the incidence of skin cancer continues to rise in Australia and it will be several years before the true effectiveness of preventative programs are known. In the meantime, 1000 Australians die each year from skin cancer. Modern sunscreens, even those with high SPF and labelled as bro ....Australia has the highest incidence of skin cancer in the world. This results from immigration of individuals with fair skin to Australia. Skin cancer is three times as common as all other cancers combined. Overall, the incidence of skin cancer continues to rise in Australia and it will be several years before the true effectiveness of preventative programs are known. In the meantime, 1000 Australians die each year from skin cancer. Modern sunscreens, even those with high SPF and labelled as broad spectrum do not protect very well from UVA, though they are very effective UVB filters. Most sunscreens absorb or reflect only about 50% as much UVA as UVB. Thus sunscreen use alters the spectrum of UV received. This is an important issue, because if sunscreens are used to prolong sun exposure they will selectively increase the amount of UVA reaching the skin, and the sun contains a lot more UVA than UVB. There is only limited evidence to suggest they protect from skin cancer in humans whereas there is good evidence that they protect from precursor lesions. We have developed a new hypothesis, that UVB is primarily responsible for development of preneoplastic lesions (solar keratosis and dysplastic nevi) whereas UVA plays a relatively more important role in their progression to malignancy. This hypothesis would explain why sunscreens are more effective at preventing nevi and solar keratosis formation than they are at preventing melanoma and squamous cell carcinoma. Until the action spectrum defining the wavelengths responsible for skin cancer induction is known, the optimal methods for protection from skin cancer will be difficult if not impossible to design. That different wavelengths may be involved in different phases of skin cancer development in humans is a novel hypothesis: if it is correct it will have profound implications for both the design of sunscreens and our current public health programmes for skin cancer prevention.Read moreRead less
Clarifying Molecular Role Of IGF-1:Ea Isoforms In Skeletal Muscle Hypertrophy And Atrophy
Funder
National Health and Medical Research Council
Funding Amount
$394,718.00
Summary
The growth factor IGF-1 is proposed as a therapeutic agent to increase muscle mass and to reduce muscle wasting resulting from denervation, disuse, ageing and dystrophy. Understanding the precise mechanisms of IGF-1 action is essential for the potential therapeutic use of this factor. This research is focused on the molecular role of IGF-1 in healthy muscle and in the conditions of muscle wasting and degeneration.