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.
The Calcium Channel TRPV4 In Skeletal Development And Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$683,069.00
Summary
We have discovered that mutations in a calcium channel gene, TRPV4, cause an inherited osteoarthritis in the hands and feet. This work suggests that TRPV4 may be important in osteoarthritis and suggests the exciting possibility that modulating TRPV4 activity may provide a new therapeutic approach for arthritis. We will study how and why the mutations disrupt channel function and study mouse models to see if they are more or less susceptible to arthritis.
Fibre-Polymer Composites With Graded Microstructure. This project concerns the development of a novel fibre-polymer functionally graded composite material that mimics the structure of the spinal disk. The spinal disk comprises a soft core (nucleus) and a tough fibrous periphery (annulus). The graded composite approach of this proposal represents a significant advance over spinal fusion, and over the current generation of spinal disk protheses (metal plates with springs/polymers as shock absorber ....Fibre-Polymer Composites With Graded Microstructure. This project concerns the development of a novel fibre-polymer functionally graded composite material that mimics the structure of the spinal disk. The spinal disk comprises a soft core (nucleus) and a tough fibrous periphery (annulus). The graded composite approach of this proposal represents a significant advance over spinal fusion, and over the current generation of spinal disk protheses (metal plates with springs/polymers as shock absorbers). Chronic back pain affects a significant proportion of the population and is primarily caused by failure of the spinal disk. Therefore a strong social and economic imperative exists to develop engineering solutions to this problem.Read moreRead less
Patient-specific biomechanical modelling for improved treatment of spinal deformity. Spinal deformities negatively affect social acceptance, physical and mental wellbeing in children and adolescents. The direct costs of spinal deformity surgery are approximately $30 million per year in Australia, yet poor treatment outcomes due to post-operative complications incur a much higher cost as patients with persistent pain and disability face a lifetime of dependency and reduced ability to work. The pa ....Patient-specific biomechanical modelling for improved treatment of spinal deformity. Spinal deformities negatively affect social acceptance, physical and mental wellbeing in children and adolescents. The direct costs of spinal deformity surgery are approximately $30 million per year in Australia, yet poor treatment outcomes due to post-operative complications incur a much higher cost as patients with persistent pain and disability face a lifetime of dependency and reduced ability to work. The patient-specific biomechanical modelling techniques developed in this project will reduce complications and improve correction for Australian children who undergo spinal deformity surgery. Better treatment outcomes will ensure quality of life, health and productivity for spinal deformity patients throughout their entire lives.Read moreRead less
The virtual human knee. This project aims to investigate the Virtual Human Knee (VHK) which provides a baseline knowledge about knee mechanics in healthy individuals and a tool for studying knee mechanics in silico. The new knowledge can be used for identifying individuals most at risk for injury, developing solutions for preventing injury and for assessing knee reconstruction and implantation methods. As such, VHK will mitigate the burden of knee injury to Australia and worldwide by progressing ....The virtual human knee. This project aims to investigate the Virtual Human Knee (VHK) which provides a baseline knowledge about knee mechanics in healthy individuals and a tool for studying knee mechanics in silico. The new knowledge can be used for identifying individuals most at risk for injury, developing solutions for preventing injury and for assessing knee reconstruction and implantation methods. As such, VHK will mitigate the burden of knee injury to Australia and worldwide by progressing disciplines including anatomy, bio-mechanics, sport science, rehabilitation, surgery and medical devices.Read moreRead less
Inter-fragmentary movement in callus formation in the early phase of fracture healing. Computational models of the early phase of bone fracture healing can provide the means to characterise the biochemical factors that control this process, and subsequently influence successful healing outcomes, with or without surgical intervention. This unique approach, incorporating soft tissue and fixation device contributions to fracture healing, will ultimately provide a sound basis for clinical decision-m ....Inter-fragmentary movement in callus formation in the early phase of fracture healing. Computational models of the early phase of bone fracture healing can provide the means to characterise the biochemical factors that control this process, and subsequently influence successful healing outcomes, with or without surgical intervention. This unique approach, incorporating soft tissue and fixation device contributions to fracture healing, will ultimately provide a sound basis for clinical decision-making, implant design and future experimental studies. Facilitating treatment optimisation, the outcomes of this project will create opportunities to reduce healthcare costs, physical impairment, and productivity losses for the 150,000 Australian patients hospitalised annually with fractures.Read moreRead less
Formation of bone-like materials for bone repair and regeneration. A successful outcome for this project would lead to the production and application of new bone-like calcium phosphate materials. Enhanced bioactivity of this material would lead to higher but controlled rates of calcium phosphate release. An understanding of the formation process of these materials and the controlled release of calcium phosphates has the potential to slow the development of metabolic diseases such as osteoporosis ....Formation of bone-like materials for bone repair and regeneration. A successful outcome for this project would lead to the production and application of new bone-like calcium phosphate materials. Enhanced bioactivity of this material would lead to higher but controlled rates of calcium phosphate release. An understanding of the formation process of these materials and the controlled release of calcium phosphates has the potential to slow the development of metabolic diseases such as osteoporosis. The WHO reports that osteoporosis is the second largest health care problem world-wide. In 2002, 44 million people in the USA were estimated to be at risk. This and similar figures in Australia and around the world emphasize the urgency of understanding and appropriately combating weak bone degenerative diseases.Read moreRead less
Targeting Calcineurin For Improving Muscle Regeneration In Skeletal Muscle Disease
Funder
National Health and Medical Research Council
Funding Amount
$303,000.00
Summary
Muscular dystrophy is a term that covers a diverse group of inherited disorders characterised by progressive muscle weakness and wasting. Duchenne muscular dystrophy (DMD) is the most severe form, caused by a lack of a protein called dystrophin, which renders muscles fragile, susceptible to damage, and with a compromised ability to regenerate or repair after injury. The disease progresses to all muscles and DMD patients are dependent on a wheelchair before their early teens and die in their twen ....Muscular dystrophy is a term that covers a diverse group of inherited disorders characterised by progressive muscle weakness and wasting. Duchenne muscular dystrophy (DMD) is the most severe form, caused by a lack of a protein called dystrophin, which renders muscles fragile, susceptible to damage, and with a compromised ability to regenerate or repair after injury. The disease progresses to all muscles and DMD patients are dependent on a wheelchair before their early teens and die in their twenties. There is a profound need for treatments that can ameliorate the dystrophic condition and improve patient quality of life. Restoring or increasing a muscle's capacity to regenerate would help improve muscle function. We have convincing evidence that the calcineurin signal transduction pathway is important for successful muscle regeneration in mice with muscular dystrophy. There is growing excitement worldwide that stimulating calcineurin could attenuate the dystrophic pathology, however, little is known about the role of calcineurin signalling in human muscle disease. Our goals are to investigate the role of calcineurin signalling in muscular dystrophy and to examine its therapeutic potential for enhancing muscle regeneration. Our aim is to better understand the mechanisms controlling calcineurin signalling in muscles of dystrophic mice and in muscles of patients with DMD. A comprehensive series of physiological, molecular, biochemical, and immunohistochemical experiments will be performed to rigorously test our research aim. Understanding the role of the calcineurin pathway in muscle regeneration is important for the development of novel therapeutic strategies to delay the onset or slow the progression of muscle wasting and weakness. The findings will have broad clinical application for our understanding of muscular dystrophy with relevance to other conditions including ageing, AIDS, burns, cancer cachexia, and disuse atrophy, where muscle wasting occurs.Read moreRead less
Advanced micro-architecture and nanotopography for enhanced tissue growth in scaffolds. Tissue engineering scaffolds offer an urgently needed synthetic biomaterials solution to overcome disease transmission from donor transplants. This work will combine biomaterial chemistry and designed surface topography to trigger bone formation within a scaffold for the first time in the world. Collaboration with national research leaders on stem cell and animal testing of the new scaffolds will provide the ....Advanced micro-architecture and nanotopography for enhanced tissue growth in scaffolds. Tissue engineering scaffolds offer an urgently needed synthetic biomaterials solution to overcome disease transmission from donor transplants. This work will combine biomaterial chemistry and designed surface topography to trigger bone formation within a scaffold for the first time in the world. Collaboration with national research leaders on stem cell and animal testing of the new scaffolds will provide the necessary interdisciplinary approach to generate a new product for patients in need of bone regeneration. Australia will benefit from the contribution to medical science, the development of a new device for rapid prototyping tissue engineering scaffolds, retain biomaterials research expertise, and generate new biomedical products.Read moreRead less
Molecular Genetic Characterisation Of A Novel X-linked Skeletal Myopathy
Funder
National Health and Medical Research Council
Funding Amount
$158,104.00
Summary
This project aims to identify the genetic basis of a new disease that is characterised by episodes of muscular weakness. This disease only affects males. The signficance of the project is that this is the first description of such a disorder and gives us an opportunity to study a previously unsuspected aspect of human muscle function.