Cellular Cross-talk Between Liver Progenitor Cells And Hepatic Stellate Cells Is Required For Hepatic Fibrogenesis
Funder
National Health and Medical Research Council
Funding Amount
$618,517.00
Summary
Deloitte Access Economics data proposes the total economic burden of liver disease in Australia in 2012 was >$50 billion. This study will identify how the liver heals itself by inducing liver cell populations which interact to regenerate damaged liver tissue in chronic liver disease. This knowledge may lead to the development of novel therapeutic interventions for the treatment of liver scarring and liver cancer, and to assist in normal liver regeneration following chronic liver disease.
Role Of Hepatic Stellate Cell And Liver Progenitor Cell Interactions In The Regulation Of Wound Healing And Liver Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
The liver has a remarkable capacity for regeneration following acute and chronic liver injury, however, the mechanisms which facilitate this wound healing are not understood. This project will examine the interactions between different liver cell populations, including hepatic stellate cells (liver fibroblasts) and liver progenitor cells (stem cells of the liver) and will determine which factors regulate inflammation, liver scarring and restitution of liver mass following chronic liver injury.
When Prometheus Needs A Hand – How Human Amnion Epithelial Cells Resolve Fibrosis And Regenerate The Liver
Funder
National Health and Medical Research Council
Funding Amount
$530,653.00
Summary
Cirrhosis can progress to end stage disease for which transplantation provides the only hope for survival. Liver donors in Australia are scarce; the need for donor organs is increasing. Using stem cells to repair and regenerate damaged liver may provide an alternative to organ transplantation. We are studying placental stem cells that can decrease inflammation and increase progenitor cells to repair and regenerate liver. Our goal is to use these stem cells as treatment for human liver disease
Functional Effects Of Polymorphic Variation Of The Aromatase (CYP19) Gene On Enzyme Activity:relationship To Disease
Funder
National Health and Medical Research Council
Funding Amount
$237,708.00
Summary
After menopause, oestrogen synthesis changes from an ovarian to an adipose source by concersion of androgens to estrogens, a process catalyzed by aromatase, the product of the CYP19 gene. We will generate mutants of the CYP19 gene that we have previously found in humans by site-directed mutagenesis and observe the effects of these mutants on aromatase function. This research will help with diagnosis and treatment of breast and other cancers and osteoporosis in humans .
Translocated signals regulating stem cell (meristem) activity in legumes. Translocation channels of phloem and xylem allocate nutrients to growing plant organs. They also mediate communication between organs through transport of signals that elicit responses to developmental and environmental cues. The most important sites for signal transduction are the stem cells of root and shoot apical meristems. This project will discover and identify these signals using a metabolomic/proteomic approach an ....Translocated signals regulating stem cell (meristem) activity in legumes. Translocation channels of phloem and xylem allocate nutrients to growing plant organs. They also mediate communication between organs through transport of signals that elicit responses to developmental and environmental cues. The most important sites for signal transduction are the stem cells of root and shoot apical meristems. This project will discover and identify these signals using a metabolomic/proteomic approach and relying on a unique feature of lupin that permits collection of transport fluids. The project will identify ways to modify signal action to enhance performance of legumes.Read moreRead less
Examination Of The Molecular Pharmacology Of Anthracyclines Induced Via Their Interaction With Iron
Funder
National Health and Medical Research Council
Funding Amount
$618,401.00
Summary
Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and ....Anthracyclines are highly effective anti-cancer drugs, but their use is limited by toxic effects on the heart. This is thought to be due to these drugs directly binding iron (Fe). Indeed, we showed that anthracyclines induced marked changes in the way heart cells utilise Fe (DR1-3, 38; Mol. Pharmacol. 2002, 2003, 2004, 2005). We were the first to show that anthracyclines prevent Fe release from the criticial Fe storage protein ferritin. This prevents the use of Fe for vital processes eg. DNA and haem synthesis. Hence, this effect probably contributes to the cytotoxic activity of anthracyclines on the heart. We showed that novel drugs developed in my lab that bind Fe called chelators show high activity in animals (DR4) and prevent anthracycline-mediated Fe accumulation in ferritin. Importantly, Fe chelators have been shown to inhibit anthracycline-mediated cardiotoxicity. Indeed, the clinically used cardioprotective agent, ICRF-187, is actually an Fe chelator (5, DR6). However, ICRF-187 is not totally successful in terms of its cardioprotective effects and can cause myelosuppression (5, DR6). While the clinically used chelator, desferrioxamine (DFO), can prevent anthracycline-mediated cardiotoxicity, its poor membrane permeability limits its effectiveness. Our chelators are highly permeable and overcome the disadvantages of DFO (DR4). Thus, they are vital to examine for preventing anthracycline-mediated cardiotoxicity. In this proposal we will examine the changes in Fe metabolism induced by anthracyclines and test the hypothesis that novel Fe chelators may prevent the cardiotoxicity of these agents. We also aim to be the first to assess if preparation of anthracyclines which cannot bind iron prevents their cardiotoxicity. This will be done by preparing metal complexes of these drugs which prevent Fe-binding eg. anthracycline-zinc complexes. These studies are important for the development of less cardiotoxic forms of these very useful anti-tumour agents.Read moreRead less
Understanding The Acute And Cumulative Metabolic Effects Of Prolonged Sitting In Adults
Funder
National Health and Medical Research Council
Funding Amount
$416,597.00
Summary
Sedentary behaviour (sitting time) has been linked to an increased risk of chronic illnesses, including type 2 diabetes and obesity, but recent evidence suggests that light-intensity activity (non-exercise activities of daily living) is associated with reduced risk. These studies will examine whether breaking up sitting time with frequent short periods of activity can overcome the negative effects of prolonged sitting on blood glucose and blood fats in overweight older adults.
Is transport of miRNAs essential for plant development? This project will provide knowledge of how a new class of biologically active molecule (micro RNA) regulates expression of genes at sites in the plant that are critical for growth and development. MicroRNAs are believed to influence the size and shape of plants, how rapidly they grow and how well they produce and fill seeds. These molecules are part of a group of bioactive signals that move throughout the plant, functioning like hormones bu ....Is transport of miRNAs essential for plant development? This project will provide knowledge of how a new class of biologically active molecule (micro RNA) regulates expression of genes at sites in the plant that are critical for growth and development. MicroRNAs are believed to influence the size and shape of plants, how rapidly they grow and how well they produce and fill seeds. These molecules are part of a group of bioactive signals that move throughout the plant, functioning like hormones but directly influencing how well critical genes work. Their exploitation holds great promise for manipulating plant performance and enhancing crop yields. Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560987
Funder
Australian Research Council
Funding Amount
$156,697.00
Summary
Robust High Resolution Gene and Protein Expression Analysis Facilities in WA. Biological research is playing an increasingly important role in keeping agriculture internationally competitive and helping to unravel the basic mechanisms underpinning plant and animal health. This collaborative research equipment will greatly enhance and extend our existing functional genomic facilities in WA, allowing robust pre-fractionation of samples for directed proteomic analysis within complex systems and al ....Robust High Resolution Gene and Protein Expression Analysis Facilities in WA. Biological research is playing an increasingly important role in keeping agriculture internationally competitive and helping to unravel the basic mechanisms underpinning plant and animal health. This collaborative research equipment will greatly enhance and extend our existing functional genomic facilities in WA, allowing robust pre-fractionation of samples for directed proteomic analysis within complex systems and allowing accurate and sensitive measurement of gene expression. Both of these are critical for analysis of low abundance components involved in signalling and regulatory functions in biological samples.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453722
Funder
Australian Research Council
Funding Amount
$385,240.00
Summary
Collaborative Genomics, Proteomics and Metabolomics Facility for Western Australia. Plant and animal agriculture in Western Australia contributes $6billion per annum to the nation. Biotechnology is playing an increasingly important role in keeping agriculture internationally competitive, and requires investment in platform technologies to underpin basic and applied research. This collaborative project will provide state-of-the-art equipment and extend existing joint facilities that will enable ....Collaborative Genomics, Proteomics and Metabolomics Facility for Western Australia. Plant and animal agriculture in Western Australia contributes $6billion per annum to the nation. Biotechnology is playing an increasingly important role in keeping agriculture internationally competitive, and requires investment in platform technologies to underpin basic and applied research. This collaborative project will provide state-of-the-art equipment and extend existing joint facilities that will enable WA researchers to carry out high quality research on genomics, proteomics and the metabolic functioning of plants and animals. This will generate new knowledge, provide advanced training and help ensure that Australian R&D in agricultural biotechnology stays at the forefront and benefits the nation.Read moreRead less