The discoveries made to date and the proposed studies point to an intrinsic role for vitamin D compounds in skin in providing protection from sun damage. As a result of sun exposure, increased concentrations of vitamin D compounds in skin will be generated and this is likely to provide protection against further UV damage, in much the same way as increased pigmentation and increased thickness of the outer layer of skin. Furthermore, the studies are designed to test whether vitamin D compounds wh ....The discoveries made to date and the proposed studies point to an intrinsic role for vitamin D compounds in skin in providing protection from sun damage. As a result of sun exposure, increased concentrations of vitamin D compounds in skin will be generated and this is likely to provide protection against further UV damage, in much the same way as increased pigmentation and increased thickness of the outer layer of skin. Furthermore, the studies are designed to test whether vitamin D compounds which have minimal effects on serum calcium, could nevertheless be used topically in association with a sunscreen or moisturizer to add to sun protection. As Australia has the highest skin cancer rates in the world, this would be of significant health and economic value.Read moreRead less
Mechanisms Of Photoprotection By Vitamin D And Analogs
Funder
National Health and Medical Research Council
Funding Amount
$438,186.00
Summary
Our discoveries have clearly shown that vitamin D compounds produced in skin due to UV exposure, have a role in protecting skin from further UV damage. The studies are designed to further examine the mechanism of this photoprotective effect, as it appears to be novel. This will aid in the developmentof agents, which could be used as an after-sun lotion to gain some protection. As Australia has the highest skin cancer rates in the world, this would be of significant health and economic value.
Mechanisms Defining Microfibril And Elastic Fibre Assembly, Structure And Function.
Funder
National Health and Medical Research Council
Funding Amount
$619,721.00
Summary
Elastic fibres are important in tissues such as arteries, lung and skin where they provide elasticity. Disruption of their normal structure and function is a major aspect of common diseases such as atherosclerosis, aneurisms, heart valve prolapse, emphysema, and the congenital disorder, Marfan syndrome. Elastic fibres consist of a core of the protein elastin surrounded by 12 nm glycoprotein microfibrils. During development the microfibrils always appear before the elastin and seem to act as a sc ....Elastic fibres are important in tissues such as arteries, lung and skin where they provide elasticity. Disruption of their normal structure and function is a major aspect of common diseases such as atherosclerosis, aneurisms, heart valve prolapse, emphysema, and the congenital disorder, Marfan syndrome. Elastic fibres consist of a core of the protein elastin surrounded by 12 nm glycoprotein microfibrils. During development the microfibrils always appear before the elastin and seem to act as a scaffold for the deposition of its precursor, tropoelastin. However knowledge of the role of each glycoprotein in the assembly, architecture, function and cell biology of microfibrils and elastic fibres is still very limited. Our laboratory has identified, cloned and characterised several microfibrillar proteins and we are uniquely placed to exploit our expertise and unique range of research tools to elucidate the mechanisms involved in the above processes. The Specific Aims are to determine a) the roles of individual components and associated proteins in microfibril and elastic fibre biology b) the architecture of microfibrils and the relationship of their structural heterogeneity to function during tissue development, c) the mechanisms responsible for microfibril and elastic fibre assembly, and other microfibril interactions with the cell surface, d) the gene regulatory mechanisms controlling expression of individual microfibrillar proteins and e) causative mutations of non-fibrillin genes in Marfan-like congenital disorders. The research will greatly increase our fundamental knowledge of the factors controlling the complex molecular mechanisms involved in microfibril assembly and elastic fibre formation, including the roles of individual microfibril-associated proteins, cell surface receptors, cellular processing, and gene regulation of these processes during normal development, which is essential before the full role of elastic fibres in major diseases can be understood.Read moreRead less
NEURAL MODULATION OF HEARING LOSSES INDUCED BY LOUD SOUND
Funder
National Health and Medical Research Council
Funding Amount
$290,500.00
Summary
Loud sounds, from occupational and recreational sources, are the most common threat to hearing and can result in temporary hearing losses (as might be experienced after an evening at a noisy pub or concert) or permanent hearing losses (after prolonged or multiple loud sounds, as for example in a noisy work environment). Noise reduction programs are either not always possible or effectively applied. A parallel strategy is the study of biological mechanisms that may ameliorate hearing damage, with ....Loud sounds, from occupational and recreational sources, are the most common threat to hearing and can result in temporary hearing losses (as might be experienced after an evening at a noisy pub or concert) or permanent hearing losses (after prolonged or multiple loud sounds, as for example in a noisy work environment). Noise reduction programs are either not always possible or effectively applied. A parallel strategy is the study of biological mechanisms that may ameliorate hearing damage, with a view to optimising such mechanisms. I propose to build on seminal Australian work to examine how one such system, nerves from the brain to the inner ear (the site of most damage from loud sounds), modulates hearing losses caused by loud sounds. Early studies indicated these nerves could protect from damage induced by short-lasting loud sound and this has led to international interest in functional applications of such protection to reduce hearing damage suffered by humans. However, my recent work indicates the nerves exert complex protective and exacerbative effects to loud sounds similar to common trauma or occurring under conditions similar to common trauma. They even exacerbate hearing losses due to loud sound, especially when there is an imbalance in hearing sensitivity in the two ears (bilateral) similar to what is common in humans. These findings make it critical that functional application be delayed until the full range of effects exerted by the nerves is understood. I propose to elucidate the novel complex effects of these nerves to loud sound. Specific aims are: (1) To understand effects of these pathways to loud sounds like those encountered by humans, (2) To investigate how chronic imbalanced bilateral hearing sensitivity, like that common in humans, alters effects of the nerves and when they change from being protective to exacerbative, (3) To adduce how an atraumatic sound affects hearing losses due to later loud sound and the role played by these nerves.Read moreRead less
Identification Of A Gene That Increases Risk Of MS Via A Pathway Involving UV Exposure
Funder
National Health and Medical Research Council
Funding Amount
$111,000.00
Summary
Multiple sclerosis (MS) is an auto-immune disease of the central nervous system that affects over 10 000 Australians. It is a progressive debilitating disease that affects predominantly young adults and current therapies are expensive, only moderately effective and are associated with significant side effects. The biological processes leading to this disease are not well understood and there is a need to identify new ways of treating the disease or preventing it. One of the known factors associa ....Multiple sclerosis (MS) is an auto-immune disease of the central nervous system that affects over 10 000 Australians. It is a progressive debilitating disease that affects predominantly young adults and current therapies are expensive, only moderately effective and are associated with significant side effects. The biological processes leading to this disease are not well understood and there is a need to identify new ways of treating the disease or preventing it. One of the known factors associated with MS is the striking association of increased MS incidence with cooler climates and reduced sun exposure. A study conduced by the Menzies Centre has recently provided evidence that increased childhood sun exposure is significantly associated with reduced risk of MS. This project aims to study those genes involved in the body's response to sun exposure as we propose that if sun exposure influences risk of MS then those genes may interact with sun exposure to modify risk of MS.Read moreRead less