Vitamin D Synthesis Within Osteoblasts Increases Bone Mineral By Regulating Remodelling: Is This The Link Between Vitamin D Status And Fractures?
Funder
National Health and Medical Research Council
Funding Amount
$627,082.00
Summary
This project will contribute to understanding mechanism of vitamin D action within bone to modulate bone resorption and offers the exciting prospect of identifying the mechanism by which an adequate vitamin D status can reduce the risk of osteoporotic hip fractures. Thus, this project has great potential to improve community health by being able to recommend vitamin D supplementation made on the basis of maintaining normal bone cell function with psarticular reference to modulating bone resorpti ....This project will contribute to understanding mechanism of vitamin D action within bone to modulate bone resorption and offers the exciting prospect of identifying the mechanism by which an adequate vitamin D status can reduce the risk of osteoporotic hip fractures. Thus, this project has great potential to improve community health by being able to recommend vitamin D supplementation made on the basis of maintaining normal bone cell function with psarticular reference to modulating bone resorption.Read moreRead less
A Transgenic Mouse Model For Studying The Role Of Human Chymase In Regulating Tissue Angiotensin II Formation
Funder
National Health and Medical Research Council
Funding Amount
$536,063.00
Summary
Cardiac hypertrophy or heart enlargement is an important risk factor in the eventual development of heart failure. It is now well known that heart enlargement can be produced by pressure overload of hypertension and-or by increased hormonal inputs directly to the heart. Angiotensin II, a hormone that produces hypertension and heart enlargement, was previously thought only to be produced by the enzyme ACE. Although ACE inhibitors are widely used in treatment of hypertension and heart failure seve ....Cardiac hypertrophy or heart enlargement is an important risk factor in the eventual development of heart failure. It is now well known that heart enlargement can be produced by pressure overload of hypertension and-or by increased hormonal inputs directly to the heart. Angiotensin II, a hormone that produces hypertension and heart enlargement, was previously thought only to be produced by the enzyme ACE. Although ACE inhibitors are widely used in treatment of hypertension and heart failure several studies now show that ACE inhibition only partially reduces angiotensin II levels in humans. Our recent studies suggest that the novel enzyme human chymase may be involved in regulating angiotensin II levels in human tissues including the heart and blood vessels. By introducing a gene for human chymase in mice we plan to create a mouse model that allows us to understand the importance of human chymase in cardiovascular physiology and disease. This mouse model would not only show the involvement of human chymase in regulating heart and vessel angiotensin II levels and in the development of hypertension and heart enlargement but also will provide an animal model essential for the development of human chymase inhibitors.Read moreRead less
The Role Of Neuronal Nicotinic Receptor Subunits In The Self-Administration And Relapse To Alcohol Seeking:Treatments For Alcohol Dependence
Funder
National Health and Medical Research Council
Funding Amount
$531,787.00
Summary
The World Health Organization reports that alcohol causes almost two million deaths every year and results in physical disability or shortened life span for at least 58 million others. Despite the fact that addiction represents more than 40% of brain-related illnesses, there is a dearth of innovative treatments. The overall goal of my research is to develop more effective medications for the treatment of alcohol use disorder by targeting the neuronal nicotinic receptor subtypes that have been sp ....The World Health Organization reports that alcohol causes almost two million deaths every year and results in physical disability or shortened life span for at least 58 million others. Despite the fact that addiction represents more than 40% of brain-related illnesses, there is a dearth of innovative treatments. The overall goal of my research is to develop more effective medications for the treatment of alcohol use disorder by targeting the neuronal nicotinic receptor subtypes that have been specifically altered by heavy alcohol intake.Read moreRead less
The cross-disciplinary team performing this research will examine how mobile DNA elements found in brain cells move in response to learning and memory exercises in mice, and whether these changes generate an address system for parts of the brain to be turned on by specific experiences. This work has major implications for our fundamental understanding of how the brain works in healthy individuals, as well as people affected by neurodevelopmental and neurodegenerative conditions.
Defining The Cellular Basis For Therapeutic Angiogenesis: Characterisation Of Endothelial Progenitor Cell Populations
Funder
National Health and Medical Research Council
Funding Amount
$100,943.00
Summary
Cardiovascular disease is the leading cause of death in the Australia. Endothelial progenitor cells (EPCs), similar to stem cells, have strong self-renewal capabilities and the ability to mature further. There has been immense interest in using EPCs as they are believed to have a role in the growth and repair of blood vessels. This research systematically studies two candidate EPCs, the early EPC and the outgrowth EPC (OEC), and potentially paves the way for using EPCs to treat heart disease.
Development Of Therapeutically Useful Human Artificial Chromosomes For Gene Delivery And Optimal Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$496,986.00
Summary
Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in ....Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in terms of infection, immune response, and germline modification. We have developed the first stage of a new technology for gene delivery that does not require the use of viruses. This technology is based on the generation of human artificial chromosomes, which are smaller versions of the naturally occurring chromosomes that carry all the genes inside our cells. Safety in these artificial chromosomes comes from the use of entirely human materials for their engineering. These artificial chromosomes also have other advantages over the viral approaches, including allowing large genes to be carried, and providing a permanent cure in a single treatment. We have already successfully constructed, published, and patented a number of first-generation human artificial chromosomes. The current project aims to complete the next proof-of-concept milestone towards the further development of this technology. Specifically, we propose to demonstrate the ability of the artificial chromosomes to carry genes and provide sustainable expression of these genes in cells and in animal models. Success in this study will allow the technology to proceed rapidly into commercialisation and clinical trial as a new improved tool for gene delivery and gene therapy.Read moreRead less
Mechanisms Of Ataxia In Spinocerebellar Ataxia Type 1 Transgenic Mice
Funder
National Health and Medical Research Council
Funding Amount
$361,158.00
Summary
Degeneration of the coordination part of the brain (cerebellum) causes ATAXIA. There are many types, but few can be cured. The majority, affecting ~ 3,000 Australians, are progressive, and can only be helped by physical therapies. We are searching for a drug to improve the SYMPTOMS of ataxia, by analysing the chemical transmitters in the cerebellum in genetically ataxic mice. If we find an imbalance, we will trial appropriate drugs to try to correct this and lessen ataxia.