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.
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.
The Molecular Mechanisms Of Anabolic Androgen Actions In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$487,500.00
Summary
We are studying the role of male sex hormones, androgens, in controlling muscle function. Muscle wasting occurs in a variety of disorders, including cancer, burns and trauma, and also during normal ageing. Treatment with androgens helps prevent muscle wasting, and causes increased muscle size, although current therapies can also have side effects. Little is known about how androgens prevent wasting and promote muscle growth. Therefore, we propose to study the actions of male sex hormones in musc ....We are studying the role of male sex hormones, androgens, in controlling muscle function. Muscle wasting occurs in a variety of disorders, including cancer, burns and trauma, and also during normal ageing. Treatment with androgens helps prevent muscle wasting, and causes increased muscle size, although current therapies can also have side effects. Little is known about how androgens prevent wasting and promote muscle growth. Therefore, we propose to study the actions of male sex hormones in muscle. We will study the growth of mouse muscle cells in culture, and measure their rate of growth when treated with androgens. All cells contain certain factors that control their growth and replication, and we will test whether androgens activate these factors to increase growth. We will also study the effect of androgens on muscle in mice, to investigate complex effects that only occur in real muscle. We will neuter male mice, which causes muscle wasting. Neutered mice will then be treated with androgens or placebo, and we will compare the muscle growth effect of androgen treatment versus placebo. We will measure muscle strength, size, and the number of muscle cells in treated and placebo mice. We will also see if the effects of androgen require a particular protein, the androgen receptor, which acts as a lock-key mechanism in cells, to allow them to respond to androgens. We will make a strain of mouse with a non-functional version of the androgen receptor only in muscle cells. This will determine if the muscle growth effects of androgens occur through a direct action on muscle, or indirectly through acting on other tissues in the body. This information will ultimately allow us to design more targeted androgen therapies for muscle wasting, that act only on muscle.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
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