It has become increasingly evident that damage to the genetic material in cells (DNA) is a fundamental initiating cause of cancer and accelerated ageing. Furthermore it has been shown recently that moderate deficiencies of certain vitamins and minerals can cause damage to DNA at a level that is observed for carcinogenic doses of radiation and toxic chemicals. In addition studies have shown that supplementation with certain vitamins resulted in a reduction of damage to DNA. The aims of this resea ....It has become increasingly evident that damage to the genetic material in cells (DNA) is a fundamental initiating cause of cancer and accelerated ageing. Furthermore it has been shown recently that moderate deficiencies of certain vitamins and minerals can cause damage to DNA at a level that is observed for carcinogenic doses of radiation and toxic chemicals. In addition studies have shown that supplementation with certain vitamins resulted in a reduction of damage to DNA. The aims of this research is to determine whether daily intake of a pill containing certain vitamins and minerals causes a reduction in DNA damage in blood cells. The expected ultimate outcome is a cancer prevention strategy based on reducing the risk of damage to DNA.Read moreRead less
FHA Domain-dependent Functions Of Cell Cycle Checkpoint Kinases
Funder
National Health and Medical Research Council
Funding Amount
$235,500.00
Summary
Human chromosomes as carriers of the genetic information are constantly subjected to DNA damage. This usually occurs spontaneously, simply as a result of oxidation of DNA residues as a byproduct of cellular energy consumption or as a result of errors during chromosome duplication in growing cells, and is compounded by chemical or physical agents, for example carcinogens, UV rays or X-rays. DNA damage can have severe consequences if not properly repaired, leading to genomic instability with loss ....Human chromosomes as carriers of the genetic information are constantly subjected to DNA damage. This usually occurs spontaneously, simply as a result of oxidation of DNA residues as a byproduct of cellular energy consumption or as a result of errors during chromosome duplication in growing cells, and is compounded by chemical or physical agents, for example carcinogens, UV rays or X-rays. DNA damage can have severe consequences if not properly repaired, leading to genomic instability with loss of vast tracts of DNA or inappropriate genome rearrangements, that may ultimately give rise to cancer. To prevent such dire consequences, all organisms from yeast to man contain molecular checkpoints that sense the presence of DNA damage and then activate a cellular response program that includes damage repair and prevention of cell division while damage persists. These molecular checkpoints are highly conserved throughout evolution which allows us to analyse the details involved in simple organisms such as yeast, to draw general conclusions on their function in more complex human cells. Along these lines, we are studying the function of two yeast proteins that are similar to the human Chk2 protein, a tumour suppressor that is mutated in a subset of families suffering from the Li-Fraumeni multi-cancer syndrome. We have identified new pathways by which these proteins contribute to the survival of cells after treatment with DNA damaging agents and will further charaterise these in the present proposal.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
A Novel Strategy For The Treatment Of Chronic Skeletal Joint Defects
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Skeletal joint injuries often heal poorly with current treatment approaches and lead to the onset of osteoarthritis. This project will produce a synthetic graft with unique properties to mimic the complex structure of joint tissues, and high bioactivity to induce optimal healing of the joint. This graft will constitute a viable alternative for the treatment of skeletal joint defects, resulting in significant healthcare benefits and improved long-term outcomes.
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.
Improving Patient Outcome Following Arthroscopic Autologous Chondrocyte Implantation
Funder
National Health and Medical Research Council
Funding Amount
$345,591.00
Summary
Autologous chondrocyte implantation (ACI) is the ‘gold standard’ for treating knee cartilage defects. Traditionally, ACI was performed through open surgery. However, ACI can now be performed through ‘keyhole’ surgery, decreasing the co-morbidity of open surgery. Furthermore, optimal patient outcome is limited by a lack of knowledge in effective post-operative rehabilitation. This project will evaluate outcomes following ACI performed through keyhole surgery, in conjunction with 'accelerated' reh ....Autologous chondrocyte implantation (ACI) is the ‘gold standard’ for treating knee cartilage defects. Traditionally, ACI was performed through open surgery. However, ACI can now be performed through ‘keyhole’ surgery, decreasing the co-morbidity of open surgery. Furthermore, optimal patient outcome is limited by a lack of knowledge in effective post-operative rehabilitation. This project will evaluate outcomes following ACI performed through keyhole surgery, in conjunction with 'accelerated' rehabilitation.Read moreRead less
IRON IN DISEASES OF THE AGEING BRAIN: From Bench To Clinic
Funder
National Health and Medical Research Council
Funding Amount
$1,814,215.00
Summary
I aim to achieve a deeper understanding of the causes, detection and treatment of incurable neurological diseases of advancing age - Alzheimer’s disease, Parkinson’s disease and Motor Neuron Disease. Iron needlessly accumulates in brain tissue with age. I will pursue studies of ageing worms, cells in culture, mice, human brain tissue, brain imaging and clinical trials, to determine whether the problem of iron accumulation is a drug target for these diseases.