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
The Role Of Sirtuin (SIRT) Proteins In The Mechanisms That Regulate Infection Induced Preterm Birth
Funder
National Health and Medical Research Council
Funding Amount
$516,430.00
Summary
Being born too early is the major cause of perinatal morbidity and mortality and accounts for the majority of neonatal deaths. The aim of this project is to gain a better understanding of the mechanisms involved in premature birth with a view to future development of clinically useful interventions to reduce the high rates of mortality and long-term disability.
Eddy-resolving global ocean-sea ice modelling. Eddy-resolving global ocean-sea ice modelling. This project aims to develop a world-class global ocean-sea ice model framework through a nationwide consortium. The resulting high resolution models are expected to provide the foundation for the next decade of Australian ocean-sea ice modelling capacity. This research should lead to improved ocean and sea ice prediction, ocean reanalyses, and climate projections, enhancing Australia's capacity to pred ....Eddy-resolving global ocean-sea ice modelling. Eddy-resolving global ocean-sea ice modelling. This project aims to develop a world-class global ocean-sea ice model framework through a nationwide consortium. The resulting high resolution models are expected to provide the foundation for the next decade of Australian ocean-sea ice modelling capacity. This research should lead to improved ocean and sea ice prediction, ocean reanalyses, and climate projections, enhancing Australia's capacity to predict the ocean state on timescales of days to decades. This is expected to yield efficiencies in shipping, marine search and rescue and naval operations, and increase the accuracy of projected future changes in climate, sea level, ocean ecosystems and the cryosphere.Read moreRead less
LIM KINASE 1 (LIMK1) AND METASTASIS, THE SEARCH FOR LIMK1 INHIBITORS
Funder
National Health and Medical Research Council
Funding Amount
$461,250.00
Summary
Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic ....Disseminated cancer, unlike the localized disease, can rarely be cured by drug therapy. We have found that LIM kinase (LIMK1), a protein that was discovered in our laboratory, plays an important role in controlling the ability of tumour cells to spread, a process called metastasis. Thus, this protein becomes an important target for the development of new drug therapies to prevent the spread of cancer. Importantly, we have demonstrated that (1) inhibiting LIMK1 blocks the formation of metastatic tumours in mice, and (2) introduction of this protein into tumour cells makes them more invasive. In addition, we find that the level of LIMK1 is much higher in human tumour cell lines that have the propensity to easily form tumours in mice. Also, measuring the level of this protein in cancer cells that spread to other organs shows that it is at significantly elevated levels when compared to normal tissue. The goals of this research are to: (1) understand whether the ability of LIMK1 to regulate tumour spreading and invasiveness correlates with its ability to control metastasis; (2) examine in human tumour samples whether the levels of LIMK1 correlate with the development of metastatic tumours; and (3) search for drugs that can inhibit the activity of this protein. The results from this research will be highly significant because LIMK1 levels are likely to be an important marker for which tumours will become metastatic. It is possible that, at the time of tumour diagnosis, LIMK1 measurements will enable the clinician to predict whether an individual tumour will become metastatic. Secondly, this protein is a novel drug development target. Drugs that inhibit this protein may block the ability of tumours to invade and metastasise.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
Revisiting the ontogeny of vocal learning in birds: from neuron to fitness. This project aims to test the hypothesis that acoustic exposure prior to hatching directly affects gene expression, neural development, behaviour and consequently fitness, in wild populations of songbirds. Recent research suggests that animals are receptive to acoustic parental signals long before birth and may use such previously unrecognised signals to make adaptive developmental decisions. This project will quantify t ....Revisiting the ontogeny of vocal learning in birds: from neuron to fitness. This project aims to test the hypothesis that acoustic exposure prior to hatching directly affects gene expression, neural development, behaviour and consequently fitness, in wild populations of songbirds. Recent research suggests that animals are receptive to acoustic parental signals long before birth and may use such previously unrecognised signals to make adaptive developmental decisions. This project will quantify the effect on neural development and vocal learning in embryonic birds, employing a model songbird species. The outcomes of this study will transform our understanding of the adaptive potential of prenatal vocal learning, which will have significant benefits for human speech and language development.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