The Chief Investigators have worked as a team for 20 years as part of a successful NHMRC Program Grant that was renewed on three successive occasions and subsequently under a NHMRC Block Grant to QIMR. Their combined expertise covers the whole spectrum from the bedside to the bench with respect to clinical studies and fundamental molecular studies of iron homeostasis. The common theme of iron homeostasis and iron overload pervades virtually all the research of the team. The team�s research has l ....The Chief Investigators have worked as a team for 20 years as part of a successful NHMRC Program Grant that was renewed on three successive occasions and subsequently under a NHMRC Block Grant to QIMR. Their combined expertise covers the whole spectrum from the bedside to the bench with respect to clinical studies and fundamental molecular studies of iron homeostasis. The common theme of iron homeostasis and iron overload pervades virtually all the research of the team. The team�s research has led to fundamental observations of iron regulation and homeostasis and the development of guidelines for the management of, and screening for, haemochromatosis, recognized as the most common inherited disorder of Caucasian populations. The proposed research encompasses molecular studies aimed at deciphering the mechanisms of iron absorption and transport; how these processes are regulated; and clinical studies on patients diagnosed with haemochromatosis. The findings are particularly pertinent to the diagnosis, management and prevention of clinical haemochromatosis.Read moreRead less
Non-HFE Haemochromatosis In Australia: Natural History And Molecular Characterisation
Funder
National Health and Medical Research Council
Funding Amount
$179,948.00
Summary
Hereditary haemochromatosis (HH) is a disorder characterised by excessive iron absorption and build up of iron in body organs such as the liver. The excess iron can be toxic and cause disease. Most HH is caused by mutations in the HFE gene. Other forms are caused by mutations in other genes. This project will characterise a new form of HH that is unrelated to any of the previously known genes. The project aims to find the gene for this new condition by genetic analysis in a large family.
Dissecting The TMPRSS6 Regulation Of Iron Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$613,311.00
Summary
Iron overload and anaemia are two of the most significant health problems affecting humans. Understanding how the body regulates iron levels is key to our understanding of these disorders and to the future development of new therapies. This research is aimed at understanding how a hormone produced in the liver called hepcidin that maintains iron balance is regulated. This research may lead to novel therapies aimed at correcting the iron balance in conditions of iron overload or anaemia
EXAMINING THE RELATIONSHIP BETWEEN MATRIPTASE-2 AND HEMOJUVELIN, TWO ESSENTIAL REGULATORS OF IRON HOMEOSTASIS
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
The control of iron levels is important in health and well being. Too little can lead to iron deficiency and anaemia, conversly too much can lead to haemochromatosis and tissue damage. We will examine the role of two proteins, matriptase-2 and hemojuvelin that when mutated cause iron deficiency or iron overload respectively. We will study how these proteins interact and work in opposite directions to control iron levels. The results will help to develop new therapeutics for iron disorders.
Industrial Transformation Research Hubs - Grant ID: IH140100035
Funder
Australian Research Council
Funding Amount
$5,000,000.00
Summary
ARC Research Hub for Computational Particle Technology. ARC Research Hub for Computational Particle Technology. This research hub aims to develop and apply advanced theories and mathematical models to design and optimise particulate and multiphase processes that are widely used in the minerals and metallurgical industries. This should be achieved through detailed analysis of the fundamentals governing fluid flow, heat and mass transfer at different time and length scales, facilitated by various ....ARC Research Hub for Computational Particle Technology. ARC Research Hub for Computational Particle Technology. This research hub aims to develop and apply advanced theories and mathematical models to design and optimise particulate and multiphase processes that are widely used in the minerals and metallurgical industries. This should be achieved through detailed analysis of the fundamentals governing fluid flow, heat and mass transfer at different time and length scales, facilitated by various novel research techniques. Research outcomes including theories, computer models and simulation techniques, as well as well-trained young researchers, should have a significant impact across a range of industries of vital importance to Australia’s economic and technological future, including the minerals, metallurgical, materials, chemical, energy, pharmaceutical and environment sectors.Read moreRead less
Uncertainty and Risk Quantifying Optimistion for Open Pit Mine Design and Production Scheduling. Open pit mine design and production scheduling (OPDPS) deals with the management of cash flows in the order of hundreds of millions of dollars, and is a critical aspect of mining ventures. To enhance decision-making under conditions of uncertainty, this proposal aims to develop a new methodology for OPDPS based on mathematical and statistical techniques which model uncertainty in key parameters, geol ....Uncertainty and Risk Quantifying Optimistion for Open Pit Mine Design and Production Scheduling. Open pit mine design and production scheduling (OPDPS) deals with the management of cash flows in the order of hundreds of millions of dollars, and is a critical aspect of mining ventures. To enhance decision-making under conditions of uncertainty, this proposal aims to develop a new methodology for OPDPS based on mathematical and statistical techniques which model uncertainty in key parameters, geological, mining and market/cost and their effects on economic forecasts. The new formulation is founded on stochastic integer programming, and its integration with spatial stochastic simulations of geological attributes. Methods developed are computerised and tested in field studies.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
Delineating The Relationship Between Iron And Peroxisomal Disorders: The Role Of The Peroxisomal Enzyme GNPAT In Iron-Overload Disorders
Funder
National Health and Medical Research Council
Funding Amount
$700,767.00
Summary
Hereditary haemochromatosis is one of the most common genetic disorders in humans, affecting 1 in 200 Australians. We have identified a change in a peroxisomal gene which may affect iron levels in humans. The prevalence of this gene change in Australian haemochromatosis patients will be examined followed by a systematic analysis of how this protein controls iron levels in the body. Our goal is to identify and diagnose genetic changes which influence iron loading in haemochromatosis patients.
Hot stage separation of non-ferrous fraction during iron ore reduction. The project aims to provide in-situ investigation of the behaviour and properties of the non-ferrous fraction in iron ore during reduction. The results aim to allow industry to: improve the quality of the final metallic iron product; economically separate and recover high-value non-ferrous impurities in the iron ore; reduce waste generated by ironmaking; and enable utilisation of, and add value to, iron ores that currently a ....Hot stage separation of non-ferrous fraction during iron ore reduction. The project aims to provide in-situ investigation of the behaviour and properties of the non-ferrous fraction in iron ore during reduction. The results aim to allow industry to: improve the quality of the final metallic iron product; economically separate and recover high-value non-ferrous impurities in the iron ore; reduce waste generated by ironmaking; and enable utilisation of, and add value to, iron ores that currently are not commercially viable due to their high impurity levels and low iron contents. The project aims to help expand the mining potential of the currently unviable iron ore deposits and enable industry to maintain the economic benefits from iron ore production in the years to come.Read moreRead less
Industrial Transformation Research Hubs - Grant ID: IH130200031
Funder
Australian Research Council
Funding Amount
$3,273,780.00
Summary
ARC Research Hub for Advanced Technologies for Australian Iron Ore. ARC Research Hub for Advanced Technologies for Australian Iron Ore. This Research Hub aims to bring together three world-class groups covering fine particle beneficiation, raw materials handling, and iron ore characterisation to address the complex issues that arise from the different ore types that have emerged in recent years. This Research Hub will focus on the development and adoption of advanced beneficiation and handling t ....ARC Research Hub for Advanced Technologies for Australian Iron Ore. ARC Research Hub for Advanced Technologies for Australian Iron Ore. This Research Hub aims to bring together three world-class groups covering fine particle beneficiation, raw materials handling, and iron ore characterisation to address the complex issues that arise from the different ore types that have emerged in recent years. This Research Hub will focus on the development and adoption of advanced beneficiation and handling technologies into iron ore mining operations, and new knowledge for informing producers and end-users, while providing the training for a new generation of research leaders.Read moreRead less