Centre For Translational Neuroscience: A Modular Platform For Translating Discovery Into Health Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$2,623,735.00
Summary
Clinical Centre of Research Excellence in Translational Neuroscience will provide people, pathways and resources to create a novel platform to take the outputs of Neuroscience Discovery programs though to improved patient outcomes for common brain diseases. A critical role will be to train and equip the best and brightest of the next generation of researchers to undertake internationally competitive translational neuroscience research that makes a difference to the health of our community.
Novel Strategies To Promote Myelin Repair In The Brain
Funder
National Health and Medical Research Council
Funding Amount
$597,865.00
Summary
Demyelinating diseases of the central nervous system such as multiple sclerosis have a lifelong impact and devastating impact on quality of life. We have identified that a growth factor, brain derived neurotrophic factor (BDNF), plays an important role in promoting myelination during development. We will investigate the potential of translating these findings into effective clinical treatment, by characterising the efficacy of BDNF in promoting CNS remyelination after a demyelinating insult.
Brain Protection: A new therapeutic approach for Multiple Sclerosis In Multiple Sclerosis (MS), the immune system mistakenly attacks the brain. The immune attacks destroy myelin, the protective coat around electrical cables in the brain (demyelination). Current treatments for MS are only partially effective, and work by reducing the number and severity of these attacks. However, MS-related permanent disability in the majority of sufferers is due to the development of progressive MS, and current ....Brain Protection: A new therapeutic approach for Multiple Sclerosis In Multiple Sclerosis (MS), the immune system mistakenly attacks the brain. The immune attacks destroy myelin, the protective coat around electrical cables in the brain (demyelination). Current treatments for MS are only partially effective, and work by reducing the number and severity of these attacks. However, MS-related permanent disability in the majority of sufferers is due to the development of progressive MS, and current therapies do not reduce this progression. It is believed that one major cause of this permanent disability is permanent myelin loss. Interestingly, we have already shown that the growth factor LIF is made by the body during MS-like inflammation, and that it limits damage by directly protecting myelin-producing cells. However, the bodies own LIF production during inflammation is sub-maximal, because myelin protection can be enhanced by giving additional therapeutic LIF. This suggests that (1) The brain produces a defence response to harmful inflammation and that (2) This defence response can be enhanced therapeutically. We therefore want to define exactly how LIF enhances myelin survival. We have measured the response to LIF in myelin-producing cells, and have discovered that it strongly stimulates the production of the small protein galanin. We will now assess if galanin itself protects myelin and myelin-producing cells, and we will test this both in isolated cells and whole animal models. If galanin production is a major mechanism by which the body tries to limit the damage from abnormal inflammation during MS, then medications that mimic the action of galanin (which are already under development for different reasons) could become a major new therapy for Multiple Sclerosis.Read moreRead less
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
How to make antibiotics in pig feed redundant, naturally. Antimicrobial resistance has become a major issue in human and veterinary medicine being partially caused by the use of in-feed antimicrobials in farm animals. This project aims to completely eliminate antimicrobials from piglet feeds. The key differential approach is based on helping the physiology of the animal rather than testing interventions against bacteria. The project will consist of developing a novel nutritional strategy of natu ....How to make antibiotics in pig feed redundant, naturally. Antimicrobial resistance has become a major issue in human and veterinary medicine being partially caused by the use of in-feed antimicrobials in farm animals. This project aims to completely eliminate antimicrobials from piglet feeds. The key differential approach is based on helping the physiology of the animal rather than testing interventions against bacteria. The project will consist of developing a novel nutritional strategy of naturally (through maternal conditioning) boosting the natural appetite and the capacity to digest in piglets early in life. The anticipated outcome is that the new peri-natal program will result in minimal bacterial proliferation and diarrhoea thus, negating the need for in-feed antimicrobials in piglets. Read moreRead less
Inflammation as an early form of maternal-fetal signalling in pregnancy. The project aims to understand the role of inflammatory signalling in marsupial pregnancy. This project is expected to explain why inflammation, a processes normally confined to injury and infection, is a part of reproduction in live-bearing mammals. Outcomes of this project include robust measures of the capacity for, impact of, and evolution of, inflammatory signalling in marsupial pregnancy. The project will provide new ....Inflammation as an early form of maternal-fetal signalling in pregnancy. The project aims to understand the role of inflammatory signalling in marsupial pregnancy. This project is expected to explain why inflammation, a processes normally confined to injury and infection, is a part of reproduction in live-bearing mammals. Outcomes of this project include robust measures of the capacity for, impact of, and evolution of, inflammatory signalling in marsupial pregnancy. The project will provide new knowledge about the unique biology of Australia's marsupial fauna.This project will provide significant benefits, including enhanced capacity for reproduction research in Australia, new international collaborations between Melbourne and Yale, and a new explanation for the puzzling role of inflammation in pregnancy.Read moreRead less
Early stress experiences and stress resilience in pigs. Animal stress has substantial implications on animal productivity, health and welfare of farm animals and thus farm profitability. This project aims to examine the stress resilience in pigs. Modern pig farming is a major source of food, providing substantial nutritional, social and economic benefits in Australia and worldwide. Animal welfare is of increasing concern to the public, consumers and pork producers, and stress vulnerability is an ....Early stress experiences and stress resilience in pigs. Animal stress has substantial implications on animal productivity, health and welfare of farm animals and thus farm profitability. This project aims to examine the stress resilience in pigs. Modern pig farming is a major source of food, providing substantial nutritional, social and economic benefits in Australia and worldwide. Animal welfare is of increasing concern to the public, consumers and pork producers, and stress vulnerability is an animal health and production problem in the life of the commercial pig. This project will generate new knowledge on early life management to endow stress resilience in pigs, with expected benefits for animal welfare, farm productivity and profitability.Read moreRead less
Developing feasible in situ control of mange disease in wombats. Our goal is the development of feasible in situ control of sarcoptic mange in wombat populations. Globally important, the Sarcoptes scabiei mite infects >100 mammal species and is among the 50 most common human diseases, causing health, welfare and population impacts. This infection is treatable, and we will test a new treatment (fluralaner), develop new models to guide management, and conduct replicated field trials. This will ena ....Developing feasible in situ control of mange disease in wombats. Our goal is the development of feasible in situ control of sarcoptic mange in wombat populations. Globally important, the Sarcoptes scabiei mite infects >100 mammal species and is among the 50 most common human diseases, causing health, welfare and population impacts. This infection is treatable, and we will test a new treatment (fluralaner), develop new models to guide management, and conduct replicated field trials. This will enable science-based guidelines, advancing disease control, local eradication, and regulatory approval for wombats. Our research framework is adaptable to other mange-impacted species, and advance methods and theory for control of treatable disease in wildlife.Read moreRead less
Early life nutrition to improve feed efficiency in commercial dairy goats. This project aims to improve the productivity and welfare and reduce resource waste in commercial dairy goat kids. The Australian dairy goat industry is expanding (~20% per annum) yet there is little research to overcome hurdles to improving milk and meat production. There is also increased societal pressure to improve sustainability, reduce waste and maintain animal welfare. By investigating nutritional methods to improv ....Early life nutrition to improve feed efficiency in commercial dairy goats. This project aims to improve the productivity and welfare and reduce resource waste in commercial dairy goat kids. The Australian dairy goat industry is expanding (~20% per annum) yet there is little research to overcome hurdles to improving milk and meat production. There is also increased societal pressure to improve sustainability, reduce waste and maintain animal welfare. By investigating nutritional methods to improve productivity of male (for meat) and female (for milk) kids, this project will generate new knowledge relevant to Australian and international goat production systems. This project will assist goat producers to make decisions that maximise animal productivity with flow on benefits to manufacturers of goat products. Read moreRead less