The Role Of SOX14 In Limb Development And Human Limb Defects.
Funder
National Health and Medical Research Council
Funding Amount
$257,606.00
Summary
Little is known about the mechanisms that control limb development. We have discovered a new gene which is active in the developing limb of the embryo. This study will provide information on how this new gene controls the development of the limb. Limb defects occur in 1 in 1,000 new-born babies. We believe the absence of our newly discovered gene may be responsible for some of these limb defects. Ultimately, this fundamental knowledge may lead to improved pre-natal diagnosis and better treament ....Little is known about the mechanisms that control limb development. We have discovered a new gene which is active in the developing limb of the embryo. This study will provide information on how this new gene controls the development of the limb. Limb defects occur in 1 in 1,000 new-born babies. We believe the absence of our newly discovered gene may be responsible for some of these limb defects. Ultimately, this fundamental knowledge may lead to improved pre-natal diagnosis and better treament for limb abnormalities.Read moreRead less
Dissecting The Role Of Hedgehog Signalling In Chondrogenesis And Skeletal Disease
Funder
National Health and Medical Research Council
Funding Amount
$408,739.00
Summary
There are close to 400 inherited disorders that affect how the skeleton develops, as well as a range of injury and age-related skeletal defects. There is much interest in treating such abnormalities with artificial bone grown outside the body. In order to achieve this aim we must understand all of the processes involved in producing and maintaining bone within the body. We are using both mouse and cell culture models of skeletal development to increase our understanding of these processes.
Hedgehog Signalling In Limb And Craniofacial Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$494,544.00
Summary
Anomalies of the face and limbs are amongst the most common features of human birth defects, and their frequent association suggests that the same genes are involved in governing the development of the limbs and face during embryogenesis. We have used a genomics-based approach to identify genes involved in limb development based on their alteration in a mouse model which develops extra fingers and toes. Defects in this mouse result from changes in Gli3, a gene which is known to be important in b ....Anomalies of the face and limbs are amongst the most common features of human birth defects, and their frequent association suggests that the same genes are involved in governing the development of the limbs and face during embryogenesis. We have used a genomics-based approach to identify genes involved in limb development based on their alteration in a mouse model which develops extra fingers and toes. Defects in this mouse result from changes in Gli3, a gene which is known to be important in both limb and face development. Based on the organs in which our genes of interest are active, we believe that they will also play key roles in embryonic development of the limbs, face and other organs. We now plan to investigate the regulation of a subset of these genes based on analysis in mouse models of limb and face development. In addition, we have chosen to further analyse the function of a completely novel gene we have identified which our preliminary studies suggest may play a role in the normal development of the lip and palate. These studies have the potential to shed light on the processes governing how organs develop, as well as on the molecular basis of common birth defects such as polydactyly (extra fingers and toes) and cleft palate.Read moreRead less
A Randomised Trial Of Constraint Induced Movement Therapy And Botulinum Toxin A In Children With Congenital Hemiplegia.
Funder
National Health and Medical Research Council
Funding Amount
$399,995.00
Summary
Congenital hemiplegia occurs in over 1 million children under 21 years of age in the industrialized world. It is the most common type of cerebral palsy, accounting for 36 percent of children diagnosed with this lifelong condition. We intend to determine if a promising new treatment approach is effective in providing a superior and lasting benefit, compared to conventional techniques. Children with hemiplegia usually have the intellectual capacity to attend normal school; however the impaired arm ....Congenital hemiplegia occurs in over 1 million children under 21 years of age in the industrialized world. It is the most common type of cerebral palsy, accounting for 36 percent of children diagnosed with this lifelong condition. We intend to determine if a promising new treatment approach is effective in providing a superior and lasting benefit, compared to conventional techniques. Children with hemiplegia usually have the intellectual capacity to attend normal school; however the impaired arm reduces independence in activities of daily living and can compromise their ability to participate in educational, leisure and vocational roles. Previously we have shown that a program of upper limb rehabilitation in children with spasticity was effective in improving participation and quality of life. We have also shown that rehabilitation combined with Botulinum toxin A (Botox) can further improve functional activity. We believe that a new method of therapy, that has been used effectively in Adults with stroke, called Constraint Induced Movement Therapy (CIMT) may also be beneficial in the treatment of children with congenital hemiplegia. In CIMT, the unimpaired arm is constrained in a glove to promote use of the impaired arm (hemiplegic arm). We predict that, combined with the Botox treatment, CIMT will provide a superior and longer lasting benefit compared to standard rehabilitation combined with Botox. The primary aim of our study is to test this hypothesis in a controlled trial. A secondary aim is to further our understanding of the central neurovascular mechanisms underlying changes in upper limb function. To achieve this, we will use Functional Magnetic Resonance Imaging (fMRI) and Transcranial Magnetic Stimulation (TMS) to measure central activation in the parts of the brain controlling movement. Improving our understanding of the mechanisms involved in this condition is an essential next step towards providing a more effective and long lasting treatment.Read moreRead less
Modelling The Loss Of NF1 Heterozygosity In Congenital Pseudarthrosis Of The Tibia (CPT).
Funder
National Health and Medical Research Council
Funding Amount
$482,978.00
Summary
Congenital pseudarthrosis of the tibia or CPT is a dibilitating orthopaedic condition that affects children. Healing of a CPT is poor and, even with modern surgical techniques, amputation is a frequent outcome. As a group experienced in animal models of bone healing, we are well positioned to develop advanced genetic models of CPT in mice. With a better understanding of the underlying processes in CPT we will be able to develop treatments for this severe childhood condition.
The Primary Cilium In Hedgehog Signalling And Disease
Funder
National Health and Medical Research Council
Funding Amount
$583,312.00
Summary
Every mammalian cell has a single protrusion called the primary cilium. Recent studies in mice and humans have highlighted the importance of the primary cilium in disease states affecting the limb, kidney, skeleton, brain, eyes, ears and lungs, as well as obesity and diabetes. We have isolated a novel mouse with a defect in the machinery required for correct functioning of the primary cilium. This mouse has widespread abnormalities and will be used to elucidate the role of cilia in disease.
Regulatory Mechanisms And Roles Of Calpains In Skeletal Muscle
Funder
National Health and Medical Research Council
Funding Amount
$439,813.00
Summary
The objectives are to understand the regulation and roles of calpains, which are proteases that break proteins in the building and repair of skeletal muscle. We will determine targets that calpains cleave and whether their location changes following activation, as well as the cellular factors regulating their activity. In addition, we will obtain information about the specific type of calpain dysfunction that occurs in particular patients with limb girdle muscular dystrophy 2A.
The Efficacy Of Novel, Non-robotic Devices To Train Reaching Post Stroke
Funder
National Health and Medical Research Council
Funding Amount
$491,605.00
Summary
Up to 50% of stroke survivors are left with upper limb disability that limits their daily activities and their paralysis is so severe that it excludes them from training with the most effective methods. This study is a clinical trial of innovative new techniques to assist people with severe upper limb paralysis to reach following stroke. Positive results are likely to reduce disability in a large number of stroke survivors and has the potential to be used by other patients with paralysis.