Deregulation Of DNA Hydroxymethylases Tet1/ Tet2 Compromises Skeletal Integrity During Ageing And Bone Disease
Funder
National Health and Medical Research Council
Funding Amount
$850,229.00
Summary
Epigenetic modifications of DNA and associated proteins regulate gene expression. A greater understanding of the molecular pathways and associated epigenetic changes that regulate bone cell commitment under normal and pathological conditions will help enhance our ability to diagnose and treat disorders/ diseases that effect skeletal tissues through the pharmacological manipulation of epigenetic modifiers and their gene targets.
Web Based Study Of Risk Factors For Pain Exacerbation In Knee Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$408,501.00
Summary
While much is known about the risk factors for radiographic knee OA, the risk factors for symptoms emanating from joints affected by OA remain unclear. Identifying modifiable methods for alleviating pain and or avoiding risk factors for exacerbations of pain could have tremendous public health importance. In the proposed study we will use the Internet to facilitate data collection to test a set of risk factors for knee pain fluctuation among subjects with symptomatic radiographic knee OA.
Novel Insights Into The Mechanisms Of How Chikungunya Virus Cause Disease In Humans
Funder
National Health and Medical Research Council
Funding Amount
$554,808.00
Summary
Many of the most dangerous and easily transmitted infectious agents are viruses. The emergence of chikungunya virus globally and the recognition of this pathogen in the aetiology of chronic diseases show the need for a better understanding of how the virus cause disease. The expected outcomes are a better understanding of human alphaviral diseases, with a view to improving prevention and treatment strategies to reduce the disease burden of CHIKV and related viruses.
Glycomic Control Of Cartilage Extra Cellular Matrix Turnover
Funder
National Health and Medical Research Council
Funding Amount
$706,289.00
Summary
Small, naturally occurring glycomic molecules control cartilage matrix turnover. We have synthesised small synthetic analogues of the naturally occurring molecules, and demonstrated their ability to regulate signalling pathways. This project will test and mathematical model the synthetic molecules in cell and tissue assays to define their properties and tissue effects, and assess their suitability as a drug delivery system. The results will be an important step towards designing new ways of trea ....Small, naturally occurring glycomic molecules control cartilage matrix turnover. We have synthesised small synthetic analogues of the naturally occurring molecules, and demonstrated their ability to regulate signalling pathways. This project will test and mathematical model the synthetic molecules in cell and tissue assays to define their properties and tissue effects, and assess their suitability as a drug delivery system. The results will be an important step towards designing new ways of treating osteoarthritis and other cartilage diseases.Read moreRead less
Targeting GDNF Family Ligand (GFL) Signalling To Treat Inflammatory Bone Pain
Funder
National Health and Medical Research Council
Funding Amount
$329,285.00
Summary
Pain associated with bone marrow oedema syndromes, osteomyelitis, osteoarthritis, fractures and bone cancer causes a major burden on individuals and health care systems in Australia and worldwide. In this application, we will explore specific signalling pathways that we have identified in nerves that code bone pain. This will provide an opportunity for the rational design of highly specific drugs capable of interacting exclusively with molecules that drive pain in these conditions.
The Role Of EphrinB1 Reverse Signalling In Osteogenic Differentiation During Skeletal Development And Osteoporosis
Funder
National Health and Medical Research Council
Funding Amount
$567,292.00
Summary
The present proposal will identify the importance of ephrinB1 during the deregulation of bone remodelling that occurs in osteoporosis, by deleting ephrinB1 in committed osteoblast precursor cells in a mouse model of osteoporosis. Knowledge gained from this proposal could potentially translate into alternative therapeutic treatment strategies for patients with osteoporosis with the use of Eph/ephrin targeted drugs currently being developed for cancer treatment.
Many human muscle diseases are caused by mutations in genes encoding skeletal muscle actin. Actin is a major building block of the sarcomere, the engine of muscle contraction. Our studies have identified a mutation in chaperonin, the main protein-folding complex responsible for actin folding, which results in a muscle defect. These results have led to a novel hypothesesis, which we test in this grant, namely that as the chaperonin complex can act as a modulator of of muscle disease.
A Randomised Controlled Trial Of Exercise Programs For Preventing Knee Injuries
Funder
National Health and Medical Research Council
Funding Amount
$1,160,491.00
Summary
The promotion of physical activity, either through organised sport or active recreation, is a key public health strategy in this country. However, there is a risk of injury during this participation and efforts need to be undertaken to reduce this risk so that spor is safe for all. Sports injury prevention efforts to date in Australia have been severely hampered by a lack of evidence supporting currently advocated countermeasures. This concern has been recognised by both the NHMRC and the Common ....The promotion of physical activity, either through organised sport or active recreation, is a key public health strategy in this country. However, there is a risk of injury during this participation and efforts need to be undertaken to reduce this risk so that spor is safe for all. Sports injury prevention efforts to date in Australia have been severely hampered by a lack of evidence supporting currently advocated countermeasures. This concern has been recognised by both the NHMRC and the Commonwealth Department of Health and Ageing. It is imperative that we formally evaluate the effectiveness of sports injury countermeasures in the context of broad community level participation in sport, in contrast to previous research focussed on professional sport, and begin to deliver the preventive measures to the community. Australian football is a popular sport throughout Australia and it is associated with more medically-treated injuries than any other sport. Knee injuries are particularly common and can have severe consequences. One of the most commonly recommended knee injury prevention strategies is a well-designed exercise training program. Despite their potential to significantly reduce injury rates, the effectiveness of exercise training programs to prevent knee injuries in football, and indeed in most other sports, has not previously been assessed but has been identified as a priority research area by the NHMRC. This project will determine the effectiveness of exercise training programs for preventing knee injuries in community-level football players by monitoring injury rates, player behaviours and player attitudes before and after the training programs are implemented.Read moreRead less
Understanding Persistent Low Back Pain Where It Resides, In The Brain
Funder
National Health and Medical Research Council
Funding Amount
$848,972.00
Summary
Low back pain is a leading cause of disability amongst Australians. A critical question is why some people get better after hurting their back while others do not. This project examines whether changes in the brain predict low back pain outcome. This information will rapidly advance our understanding of low back pain and has the potential to facilitate the development of novel therapies.
Histone Demethylase KDM6A Is A Novel Target For Treating Craniosynostosis In Children With Saethre-Chotzen Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$548,854.00
Summary
Children with Saethre-Chotzen syndrome exhibit premature fused coronal sutures, and other skull/ skeletal malformations. Surgical intervention is the only treatment option to ensure optimal cognitive and skeletal development. Our studies have identified a candidate molecular pathway that regulates bone formation by cranial bone cells from these patients. Targeting this key molecular regulator with chemical inhibitors will help prevent the premature fusion of cranial sutures.