Identification Of The Mechanisms Of Hepatic Fibrogenesis Aid In The Detection And Prediction Of Clinical Outcomes In Paediatric Cholestatic Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$624,429.00
Summary
Biliary Atresia (BA) and Cystic Fibrosis Liver Disease (CFLD) are important causes of childhood cirrhosis. Diagnosis is difficult, treatments problematic, and outcomes suboptimal. In BA, bile duct obstruction in infants rapidly progresses to liver failure. It is the most common indication for liver transplantation in children. CFLD causes significant morbidity/mortality in about 20% of CF children. This proposal investigates the mechanisms of liver fibrosis (scarring) and the role of fibrosis in ....Biliary Atresia (BA) and Cystic Fibrosis Liver Disease (CFLD) are important causes of childhood cirrhosis. Diagnosis is difficult, treatments problematic, and outcomes suboptimal. In BA, bile duct obstruction in infants rapidly progresses to liver failure. It is the most common indication for liver transplantation in children. CFLD causes significant morbidity/mortality in about 20% of CF children. This proposal investigates the mechanisms of liver fibrosis (scarring) and the role of fibrosis in both diagnosis and predicting clinical outcome.Read moreRead less
Mechanisms Of Hepatic Fibrogenesis In Chronic Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$697,209.00
Summary
Despite advances made in understanding the mechanisms of liver injury, chronic liver disease continues to be one of the most rapidly growing causes of death in subjects aged <65 years. This is the result of uncontrolled wound healing and regeneration leading ultimately to cirrhosis and liver cancer. This research will identify and characterise pathways that control the wound healing response to liver injury, involving the processes of inflammation, scarring and restitution of normal liver mas ....Despite advances made in understanding the mechanisms of liver injury, chronic liver disease continues to be one of the most rapidly growing causes of death in subjects aged <65 years. This is the result of uncontrolled wound healing and regeneration leading ultimately to cirrhosis and liver cancer. This research will identify and characterise pathways that control the wound healing response to liver injury, involving the processes of inflammation, scarring and restitution of normal liver mass.Read moreRead less
Hepatic Fibrogenesis In Paediatric Cholestatic Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$254,250.00
Summary
Liver disease in children causes a significant impact on lifespan and quality of life. The commonest causes of liver disease in children are cholestatic, or diseases related to obstruction of bile flow out of the liver. In ways we are only beginning to understand, obstruction of bile flow stimulates liver scar formation which, if untreated, leads to replacement of normal liver tissue and ultimately to failure of the liver. In infants, the most common and serious cholestatic liver disease is bili ....Liver disease in children causes a significant impact on lifespan and quality of life. The commonest causes of liver disease in children are cholestatic, or diseases related to obstruction of bile flow out of the liver. In ways we are only beginning to understand, obstruction of bile flow stimulates liver scar formation which, if untreated, leads to replacement of normal liver tissue and ultimately to failure of the liver. In infants, the most common and serious cholestatic liver disease is biliary atresia. It develops at, or shortly after birth with progressive destruction of the bile ducts, responsible for transporting bile out of the liver. Without early diagnosis and surgery these infants develop progressive liver scarring leading to liver failure and death or liver transplantation within 1-2 years. It is the commonest reason for liver transplantation in children (55-60%) in the Western world. Even with successful surgery, most, if not all patients will come to liver transplantation over the subsequent 25 years because of ongoing, but slower, scar formation. In older children, diseases like cystic fibrosis cause bile duct blockages leading to progressive liver scarring that is slower and unpredictable, contributing to ill health in up to 20% of patients and death from end stage liver disease or liver transplantation in 5%. Using liver tissue from children with these two disorders we have been able to identify the key cells that control the liver scar process, the Hepatic Stellate Cell. We now need to investigate the role of bile constituents on the scar-forming process in these two diseases. We will utilise a well characterised animal model to investigate the influence of bile constituents on cells isolated from this model and apply these findings back to patient samples to determine their role in paediatric cholestatic liver disease. This will help us to better understand the disease process and importantly, develop more effective and earlier treatment.Read moreRead less
Role Of Chemoattractants In Hepatic Stellate Cell Recruitment And Fibrogenesis In Paediatric Cholestatic Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$589,175.00
Summary
This project investigates how decreased bile flow in children's liver diseases such as cystic fibrosis and biliary atresia, leads to the release of molecules from the liver which cause recruitment of scar-forming cells. This results in cirrhosis (liver scar) and the necessity for liver transplantation. This project will investigate whether some children are more susceptible to liver scarring due to mutations in genes which cause increased release of these recruitment molecules from the liver.
I am a hepatology scientist investigating the mechanisms associated with the development of hepatic fibrosis and cirrhosis in chronic liver diseases affecting children (cystic fibrosis liver disease and biliary atresia) and adults (haemochromatosis).
Accelerated breeding for a changing environment: genomic and physiological profiling of newly generated polyploid trees. Global climate change threatens the health and productivity of forests and plantations. Because tree breeding is slow, elite trees cannot be adapted rapidly to new environments. A new procedure for accelerated tree breeding has been developed by the industry partner. The procedure, termed polyploidisation, increases DNA content and produces novel traits that can improve plant ....Accelerated breeding for a changing environment: genomic and physiological profiling of newly generated polyploid trees. Global climate change threatens the health and productivity of forests and plantations. Because tree breeding is slow, elite trees cannot be adapted rapidly to new environments. A new procedure for accelerated tree breeding has been developed by the industry partner. The procedure, termed polyploidisation, increases DNA content and produces novel traits that can improve plant growth and resilience. Polyploidisation is a natural force in plant evolution and its routine application for tree breeding has much potential. Using diverse approaches, we will investigate how newly synthesised polyploid tree species perform under heat and drought stress.Read moreRead less
Potential of Corymbia torelliana hybrids for hardwood forestry and investigation of their seed dispersal by Trigona bees. Cadaghi (Corymbia torelliana) and their hybrids with spotted gums (C. variegata complex) have enormous potential for plantation forestry. These hybrids have many excellent features that make them exciting as hardwood species, such as resistence to disease, tolerance of marginal environments, good wood properties, and fast growth rates. This project will create hybrids between ....Potential of Corymbia torelliana hybrids for hardwood forestry and investigation of their seed dispersal by Trigona bees. Cadaghi (Corymbia torelliana) and their hybrids with spotted gums (C. variegata complex) have enormous potential for plantation forestry. These hybrids have many excellent features that make them exciting as hardwood species, such as resistence to disease, tolerance of marginal environments, good wood properties, and fast growth rates. This project will create hybrids between Corymbia torelliana and spotted gums to identify hybrids which are suitable for sustainable wood production on marginal agricultural lands.
An unusual feature of Cadaghi is that native Trigona bees disperse their seeds. This project will investigate this unique seed dispersal mechanism and identify features of hybrids that are not attractive to bees. This will prevent environmental problems by preventing hybrids from dispersing seeds, becoming weedy and harming the Trigona bees.
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National Macadamia Conservation Program. Macadamia is a national icon, and the only indigenous Australian plant food crop to be commercialised. However, it is vulnerable to extinction in the wild, needing conservation action. University, government, industry and community sectors will work together applying cutting edge research methodologies to produce a systematic conservation and recovery plan for Macadamia. This requires: Habitat modelling to predict past, contemporary and potential distribu ....National Macadamia Conservation Program. Macadamia is a national icon, and the only indigenous Australian plant food crop to be commercialised. However, it is vulnerable to extinction in the wild, needing conservation action. University, government, industry and community sectors will work together applying cutting edge research methodologies to produce a systematic conservation and recovery plan for Macadamia. This requires: Habitat modelling to predict past, contemporary and potential distributions for advising resource discovery and rehabilitation; Genetic variation modelling to assess quality and distinctness of native genetic resources and potential for rehabilitation by natural colonisation; and Developing a unifying statistical framework to support this work.Read moreRead less
Site factors and genotype-site interaction affecting growth of eucalypt hybrids bred for commercial agro-forestry as a salinity management tool. Preliminary results indicate that with appropriate site-genotype matching, commercial plantation forestry can be pushed well below the current limit (650-700mm/yr). Outcomes from this project will potentially facilitate doubling of Australia's forest plantations, eliminate the annual trade deficit of $2 billion in forest products; ensure the long term e ....Site factors and genotype-site interaction affecting growth of eucalypt hybrids bred for commercial agro-forestry as a salinity management tool. Preliminary results indicate that with appropriate site-genotype matching, commercial plantation forestry can be pushed well below the current limit (650-700mm/yr). Outcomes from this project will potentially facilitate doubling of Australia's forest plantations, eliminate the annual trade deficit of $2 billion in forest products; ensure the long term environmental and productive sustainability of our agricultural production systems; diversify and drought proof farm income through the introduction of perennial tree crops whose yield and harvest is independent of short term seasonal fluctuations; and re-invigorate the economy of rural Australia brought about by investment in new, inland forest and wood processing industries.Read moreRead less
Genetic variation of the vulnerable Eucalyptus argophloia, and its development for sustainable hardwood forestry in low rainfall areas. We will examine the biodiversity in a vulnerable species of eucalypt, Eucalyptus argophloia. This species is under threat due to land clearing, and only 1000 trees remain in the wild. E. argophloia has great promise for plantation timber in low rainfall areas of Northern Australia. We will breed superior varieties for plantation forestry designed to cope with cl ....Genetic variation of the vulnerable Eucalyptus argophloia, and its development for sustainable hardwood forestry in low rainfall areas. We will examine the biodiversity in a vulnerable species of eucalypt, Eucalyptus argophloia. This species is under threat due to land clearing, and only 1000 trees remain in the wild. E. argophloia has great promise for plantation timber in low rainfall areas of Northern Australia. We will breed superior varieties for plantation forestry designed to cope with climate change, low rainfall and salinity. This project will help to manage and preserve the species in the wild and create profitable and sustainable timber plantations on marginal lands.Read moreRead less