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.
Monitoring and Maintaining the Structural Health of Bridges Using Vibration Characteristics. Bridges form an important part of our physical infrastructure system and in Queensland alone there are nearly 3000 bridges with an annual maintenance cost in excess of 20 million dollars and a replacement value in excess of 2 billion dollars. It is necessary to ensure that these bridges function safely and efficiently at all times. Bridge failure will cause disruption to normal lives and expensive repa ....Monitoring and Maintaining the Structural Health of Bridges Using Vibration Characteristics. Bridges form an important part of our physical infrastructure system and in Queensland alone there are nearly 3000 bridges with an annual maintenance cost in excess of 20 million dollars and a replacement value in excess of 2 billion dollars. It is necessary to ensure that these bridges function safely and efficiently at all times. Bridge failure will cause disruption to normal lives and expensive repairs. Towards this end, this project will develop an innovative structural health monitoring system to monitor and maintain the structural health of our bridges. The project outcomes will have immediate applications in Australia and overseas with economic and social benefits to the community.Read moreRead less
Optimisation of Rail Network Infrastructure Capacity under Dynamic Train Planning. Recent changes in railway operating environments have caused significant operational and management problems in Australia. This research will lead to improvements of railway's key managerial functions, namely: network capacity planning; rollingstock planning; train scheduling; and maintenance planning. The major outcome of the research will be to develop an optimisation model to significantly improve the operati ....Optimisation of Rail Network Infrastructure Capacity under Dynamic Train Planning. Recent changes in railway operating environments have caused significant operational and management problems in Australia. This research will lead to improvements of railway's key managerial functions, namely: network capacity planning; rollingstock planning; train scheduling; and maintenance planning. The major outcome of the research will be to develop an optimisation model to significantly improve the operating efficiency and assets productivity of Australia's rail system. The novelty of the research is that it will be undertaken using innovations based on modern job shop scheduling and sequencing optimisation techniques as the complexity of the problem makes it impossible to solve by classic optimisation techniques.Read moreRead less
Wave Climate in the Southern Great Barrier Reef. Sea surface roughness has a major influence on global climate modelling. This project will provide a better understanding of the variability of sea waves in coastal waters. New technology of HF ocean radar can map wave fields over coastal waters and thus fill a gap between the open ocean satellite measurements and the point measurements from wave buoys. In this project we will improve the analysis of the radar echoes to produce sea wave spectra, a ....Wave Climate in the Southern Great Barrier Reef. Sea surface roughness has a major influence on global climate modelling. This project will provide a better understanding of the variability of sea waves in coastal waters. New technology of HF ocean radar can map wave fields over coastal waters and thus fill a gap between the open ocean satellite measurements and the point measurements from wave buoys. In this project we will improve the analysis of the radar echoes to produce sea wave spectra, and evaluate focussing of waves by complex currents on the continental shelf to help improve wave forecasting in coastal waters. The HF radar will be used to experimentally test current theories of wind wave spreading.Read moreRead less
Assessing the full impacts of high efficiency heavy vehicles in urban traffic networks using new analytical tools. Significant economic benefits result from new innovative heavy vehicles, which are able to carry up to twice the payload of standard semi-trailers. In addition, those vehicles have the potential to reduce overall accidents and evironmental degradation. Those benefits need to be traded-off against the impacts on other road users. This research will improve the operation of such ve ....Assessing the full impacts of high efficiency heavy vehicles in urban traffic networks using new analytical tools. Significant economic benefits result from new innovative heavy vehicles, which are able to carry up to twice the payload of standard semi-trailers. In addition, those vehicles have the potential to reduce overall accidents and evironmental degradation. Those benefits need to be traded-off against the impacts on other road users. This research will improve the operation of such vehicles in regional centres by producing: (1) an assessment methodology to deal with options for network efficiency gains which will capture the full impacts; and (2) a computer modelling tool based on fundamental research to quantify those impacts, in terms of delays and accident rates.Read moreRead less
Special Research Initiatives - Grant ID: SR0354488
Funder
Australian Research Council
Funding Amount
$10,000.00
Summary
Intelligent vehicles and road infrastructure (IVRI). The aims of the network are to integrate the activities of researchers and practitioners in the areas of vehicles and road infrastructure and through cross-disciplinary collaboration apply intelligent control systems to deliver mobility, which is safer for all users, reduces driver stress and environmental impact with increased local manufactured content and improved cost effectiveness. It is of great significance to provide a cohesive solutio ....Intelligent vehicles and road infrastructure (IVRI). The aims of the network are to integrate the activities of researchers and practitioners in the areas of vehicles and road infrastructure and through cross-disciplinary collaboration apply intelligent control systems to deliver mobility, which is safer for all users, reduces driver stress and environmental impact with increased local manufactured content and improved cost effectiveness. It is of great significance to provide a cohesive solution to the transport problem considering all modes, environmental impacts, and economical and social considerations. This project should lead to a report identifying Australia's capability in this sector and a roadmap for a future research network integrating university and industry based research.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