Many new therapies are being developed to treat stroke and prevent its recurrence. While a number of these have been successfully introduced, there is a puzzling gap between evidence of efficacy in animal models and humans. One of the main reasons may be lack of an integrated approach between the basic sciences and clinical researchers. By assembling a team with skills in both areas and a structure to maximise communication between groups this team plan to incrementally introduce new therapies i ....Many new therapies are being developed to treat stroke and prevent its recurrence. While a number of these have been successfully introduced, there is a puzzling gap between evidence of efficacy in animal models and humans. One of the main reasons may be lack of an integrated approach between the basic sciences and clinical researchers. By assembling a team with skills in both areas and a structure to maximise communication between groups this team plan to incrementally introduce new therapies into clinical practice.Read moreRead less
The Role Of GRHL-3, A Mammalian Homologue Of Drosophila Grainyhead, In Neural Tube Development
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first ....Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first few hours of life. These abnormalities occur frequently (1-1000 live births) and are a direct result of failure of the neural tube to close during embryogenesis. NTDs are influenced by both environmental and genetic factors. The best characterised environmental factor is the dietary supplement folate, which when administered before conception results in a reduction in the incidence of spina bifida. The genetic complexity is evidenced by the array of mouse genetic mutations that give rise to NTDs. One of these mouse mutations, known as Curly tail (ct), has served as the major animal model of human NTDs. This is because the ct mice are resistant to folate administration (like most of the cases of spina bifida currently seen in patients) and because the mice seem to have normal development in virtually all other organ systems. Ironically, the genetic mutation that causes the curly tail phenotype has remained undiscovered for over 50 years. We have now identified the gene mutated in the curly tail mice. This gene is highly conserved in humans suggesting that it will play a similar role in neural tube development in man. The gene, known as GRHL-3, is a descendant of a fly gene critical for development of the nervous system in that organism. The studies we propose here will examine the developmental pathways involved in normal neural tube closure in mice and humans and will impact on our understanding of these devastating congenital malformations.Read moreRead less
Relationships between insulin resistance, diet and obesity in ponies and horses. There are an estimated 1.2 million horses in Australia, and the horse industry is estimated to contribute over $6.3 billion to the economy. Laminitis is a significant health and welfare problem in Australia, as it is worldwide, causing pain and lameness, loss of use, and sometimes necessitating euthanasia. Laminitis is one of the most common reasons for horse owners to seek veterinary attention, and diet and obesity ....Relationships between insulin resistance, diet and obesity in ponies and horses. There are an estimated 1.2 million horses in Australia, and the horse industry is estimated to contribute over $6.3 billion to the economy. Laminitis is a significant health and welfare problem in Australia, as it is worldwide, causing pain and lameness, loss of use, and sometimes necessitating euthanasia. Laminitis is one of the most common reasons for horse owners to seek veterinary attention, and diet and obesity increasingly predispose to this condition. Since treatment of laminitis is difficult, prevention is crucial. The outcomes from this project will include the provision of more specific advice on dietary and exercise management to vets and horse owners to reduce the incidence and impact of laminitis on the horse industry.Read moreRead less
Optimisation of a novel hybrid vaccine for liver fluke disease in cattle. Optimisation of a novel hybrid vaccine for liver fluke disease in cattle. This project aims to optimise the formulation of novel fluke vaccine antigens by constructing combination hybrid recombinant antigens and using a protein adjuvant to improve immunogenicity, and test new antigens expressed in young flukes as vaccines and evaluate their ability to synergise with hybrid vaccines. Fasciola (fluke) infections cause seriou ....Optimisation of a novel hybrid vaccine for liver fluke disease in cattle. Optimisation of a novel hybrid vaccine for liver fluke disease in cattle. This project aims to optimise the formulation of novel fluke vaccine antigens by constructing combination hybrid recombinant antigens and using a protein adjuvant to improve immunogenicity, and test new antigens expressed in young flukes as vaccines and evaluate their ability to synergise with hybrid vaccines. Fasciola (fluke) infections cause serious economic losses to livestock production and fluke drug resistance threatens control, so new therapies such as a vaccine are needed. These vaccines should be evaluated in cattle trials. The major outcome plan is validation of hybrid antigens for commercial vaccine development for fluke control in cattle, leading to more sustainable beef and milk production in Australia.Read moreRead less
Insecticide targets in the nervous system: Discovery and design for sustainable insect pest control. Insect pests impose massive costs in food production, in human health and in the wellbeing of our companion animals. Chemical insecticides remain a major weapon in the control of these pests, but the use of insecticides has some downsides. The way in which insecticides kill insects is poorly understood and insecticide usage has negative impacts in the environment – the persistence of chemical r ....Insecticide targets in the nervous system: Discovery and design for sustainable insect pest control. Insect pests impose massive costs in food production, in human health and in the wellbeing of our companion animals. Chemical insecticides remain a major weapon in the control of these pests, but the use of insecticides has some downsides. The way in which insecticides kill insects is poorly understood and insecticide usage has negative impacts in the environment – the persistence of chemical residues and the killing of beneficial insects along with the pests. Further, insects become resistant to insecticides, so pest control is lost. This proposed research seeks to identify the ‘achilles heal’ in insect pests and to target them with new generation insecticides to gain safe, effective and sustainable control.Read moreRead less
Mechanisms of manchette function. This project aims to define the function of the manchette, a poorly understood microtubule-based structure present in haploid male germ cells. This project aims to define key mechanisms underpinning manchette development and movement, and to generate a detailed picture of the dynamics of germ cell development using imaging technologies and unique animal models. Such knowledge should improve the understanding of how male fertility is achieved, the origin of infer ....Mechanisms of manchette function. This project aims to define the function of the manchette, a poorly understood microtubule-based structure present in haploid male germ cells. This project aims to define key mechanisms underpinning manchette development and movement, and to generate a detailed picture of the dynamics of germ cell development using imaging technologies and unique animal models. Such knowledge should improve the understanding of how male fertility is achieved, the origin of infertility and how species-specific differences in sperm form are achieved. Such insights may ultimately lead to improved agricultural efficiencies and job creation.Read moreRead less
Relaxin: molecular mechanisms of action in the reversal of fibrosis. Defects in relaxin and relaxin receptors are increasingly implicated as a cause of fibrosis which is associated with many disease processes. This study will examine the molecular mechanisms linking relaxin and fibrosis and will determine whether relaxin can be used to reverse the condition.
Roles Of The EMT Transcription Factors In Epigenetic Remodelling And Myeloid Cell Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$809,520.00
Summary
This project is based upon our novel discoveries that identified ZEB2 and SNAI1 as novel genes involved in the development of aggressive forms of blood cancer. During the course of this proposal we will find new drug targets and new drug treatment options using existing drugs that will specifically target cancer initiating cells in order to kill aggressive forms of blood cancers that are currently refractory to treatment.
Identifying The Pathological Mechanism Of PCDH19-Girls Clustering Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$523,988.00
Summary
Changes in the PCDH19 gene are a relatively common cause of epilepsy. To better understand the basis of this disorder, we have developed unique mouse models that mimic the genetic changes and symptoms of this condition. We will perform careful analysis of brain development in these models to determine the primary cause of this condition. These experiments will create greater understanding of how changes in PCDH19 cause epilepsy in girls and facilitate the development of new treatments.
The routes of infection with sheep scrapie and agents that cause related prion diseases. We will define the routes by which the infective agents for scrapie, a debilitating disease of sheep, reach the nervous system after being consumed with food. Scrapie is from the same disease group (prion diseases) as mad cow disease. There would be a large economic cost were prion diseases to infect agricultural animals in Australia, through bioterrorism or accident. An outbreak in sheep could ruin the indu ....The routes of infection with sheep scrapie and agents that cause related prion diseases. We will define the routes by which the infective agents for scrapie, a debilitating disease of sheep, reach the nervous system after being consumed with food. Scrapie is from the same disease group (prion diseases) as mad cow disease. There would be a large economic cost were prion diseases to infect agricultural animals in Australia, through bioterrorism or accident. An outbreak in sheep could ruin the industry, as our export markets would be immediately blocked, and thousands of animals would be killed to stop disease spread. The benefit of clearly understanding how the infective agents reach the nervous system is that this may lead to strategies to intervene, and thus limit the spread and seriousness of infection.Read moreRead less