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).
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
N-Acetyl Cysteine In Schizophrenia Resistant To Clozapine: A Double-Blind Randomised Placebo-Controlled Trial Targeting Negative Symptoms
Funder
National Health and Medical Research Council
Funding Amount
$981,789.00
Summary
Many patients with schizophrenia remain treatment resistant even after “last resort” medications like clozapine. This proposal will conduct a novel multi-site randomised placebo controlled trial of adjunctive N-acetyl cysteine in patients with clozapine resistant schizophrenia. Treatment efficacy will be examined at 8, 26 and 52 weeks.
Industrial Transformation Training Centres - Grant ID: IC160100027
Funder
Australian Research Council
Funding Amount
$4,340,802.00
Summary
ARC Training Centre for Biopharmaceutical Innovation. ARC Training Centre for Biopharmaceutical Innovation. This centre aims to transform Australia’s growing biopharmaceutical industry, an advanced manufacturing capability, by training specialist biotechnologists and bioengineers. It expects the research and development outputs will create new biopharmaceuticals and antibody-based reagents, enhanced production methods, improved manufacturing capabilities and a cohort of specialist scientists. Ne ....ARC Training Centre for Biopharmaceutical Innovation. ARC Training Centre for Biopharmaceutical Innovation. This centre aims to transform Australia’s growing biopharmaceutical industry, an advanced manufacturing capability, by training specialist biotechnologists and bioengineers. It expects the research and development outputs will create new biopharmaceuticals and antibody-based reagents, enhanced production methods, improved manufacturing capabilities and a cohort of specialist scientists. New biopharmaceuticals are expected to benefit the Australian economy and provide new therapeutic options for better health outcomes. Industry-driven research projects will also provide industry-ready graduates who can drive future growth in the sector.Read moreRead less
Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding ....Understanding how RNA editing regulates RNA fate. This project aims to address how RNA editing mediated by ADAR1 alters the interactions of targeted RNA with the innate immune sensing system. ADAR1 editing converts adenosine to inosine within double stranded RNA. It is known that this is key to prevent activation of the innate immune sensor MDA5 by endogenous RNA. However, we do not understand why edited RNA is tolerated and unedited RNA is not. This project will generate new knowledge regarding the effect of editing on how endogenous RNA is perceived by the innate immune system.Read moreRead less
Industrial Transformation Research Hubs - Grant ID: IH220100017
Funder
Australian Research Council
Funding Amount
$4,808,669.00
Summary
ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals. Radiopharmaceuticals are emerging as next generation medical technologies for addressing complex health challenges, and their manufacture offers significant economic benefit to Australia. The ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals (AMTAR) aims to establish a manufacturing platform for new medical technologies combining innovations in biotechnology and pharmaceutical science. The progra ....ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals. Radiopharmaceuticals are emerging as next generation medical technologies for addressing complex health challenges, and their manufacture offers significant economic benefit to Australia. The ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals (AMTAR) aims to establish a manufacturing platform for new medical technologies combining innovations in biotechnology and pharmaceutical science. The program addresses industry-led challenges for translation of biologics as molecular radiopharmaceuticals, building capacity in biomanufacturing, radiobiology and radiochemistry. The program establishes a dedicated manufacturing pipeline, future-proofing production and securing supply chain of next generation medical technologies.Read moreRead less
Protein biosensors for detecting smoke exposure of grapes. Bush fires and controlled burns that take place in the vicinity of vineyards can lead to grape contamination with tasteless phenolic glucosides. Their hydrolysis during wine making leads to “smoke taint” – an unpleasant medicinal taste that can render wine undrinkable. We will apply a combination of organic synthesis, protein engineering and directed evolution to develop protein-based biosensors of phenolic glucosides. These biosensors w ....Protein biosensors for detecting smoke exposure of grapes. Bush fires and controlled burns that take place in the vicinity of vineyards can lead to grape contamination with tasteless phenolic glucosides. Their hydrolysis during wine making leads to “smoke taint” – an unpleasant medicinal taste that can render wine undrinkable. We will apply a combination of organic synthesis, protein engineering and directed evolution to develop protein-based biosensors of phenolic glucosides. These biosensors will be used to devise a simple portable colorimetric test that can be performed in the vineyard or the winery. The ability to rapidly determine the level of grape contamination with phenolic glucosides would give Australian wine growers and wine makers a powerful tool to mitigate the effects of bushfires.Read moreRead less
High-throughput microfluidic approach to mapping hierarchies of interactions in the gene regulation machinery. The exploration of protein-protein interactions networks is becoming an extremely active area of research in life sciences. The current project will develop new approaches to accelerate the discovery of novel interacting proteins participating in gene regulation, in order to understand how cells differentiate into different tissues and organs.
In vitro expression of macrocyclic peptides. This project aims to develop a novel strategy for the production of polypeptides with unnatural chemical groups using a sense codon reassignment approach. Novel peptides could be used in a range of pharmaceutical applications. Peptides made of 20 natural amino acids cover only a very small fraction of the available chemical and functional space. While a peptide’s functionality can be extended with unnatural amino acids, the methods for their site-sele ....In vitro expression of macrocyclic peptides. This project aims to develop a novel strategy for the production of polypeptides with unnatural chemical groups using a sense codon reassignment approach. Novel peptides could be used in a range of pharmaceutical applications. Peptides made of 20 natural amino acids cover only a very small fraction of the available chemical and functional space. While a peptide’s functionality can be extended with unnatural amino acids, the methods for their site-selective incorporation are inefficient. The project’s strategy relies on the depletion of selected tRNAs from an in vitro protein translation system and their replacement with synthetic tRNAs, charged with unnatural amino acids. It is expected that the developed technology could be used to rapidly generate and screen highly diversified macrocyclic peptide libraries.Read moreRead less