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
Industrial Transformation Research Hubs - Grant ID: IH230100010
Funder
Australian Research Council
Funding Amount
$5,000,000.00
Summary
ARC Research Hub for Smart Process Design and Control . ARC Research Hub for Smart Process Design and Control aims to develop and apply advanced computational technologies to model and optimise complex multiphase processes by integrating the novel multiscale and AI modelling approaches. The outcomes include theories, computer models and simulation techniques, advanced knowledge about process modelling and optimisation, innovative technologies and processes for low carbon operations, and tens of ....ARC Research Hub for Smart Process Design and Control . ARC Research Hub for Smart Process Design and Control aims to develop and apply advanced computational technologies to model and optimise complex multiphase processes by integrating the novel multiscale and AI modelling approaches. The outcomes include theories, computer models and simulation techniques, advanced knowledge about process modelling and optimisation, innovative technologies and processes for low carbon operations, and tens of postdoc and PhD students through academic, industrial and international collaboration. Their application will significantly improve energy/process efficiency and reduce CO2 emission. The Hub will generate a significant impact on the mineral and metallurgical industries which are important to Australia.Read moreRead less
Industrial Transformation Training Centres - Grant ID: IC220100028
Funder
Australian Research Council
Funding Amount
$4,969,602.00
Summary
ARC Training Centre for Innovative Composites for the Future of Sustainable Mining Equipment. The Centre aims to train industry-focused researchers in advanced manufacturing of new-generation mining equipment and sustainable mining technology, through close collaborations among key universities and mining and manufacturing companies. The Centre will cultivate a team of world-class academic researchers and industry leaders to deliver an innovative program on research of innovative composites coup ....ARC Training Centre for Innovative Composites for the Future of Sustainable Mining Equipment. The Centre aims to train industry-focused researchers in advanced manufacturing of new-generation mining equipment and sustainable mining technology, through close collaborations among key universities and mining and manufacturing companies. The Centre will cultivate a team of world-class academic researchers and industry leaders to deliver an innovative program on research of innovative composites coupled with work-integrated learning, to not only produce a workforce that meets future skills demand but also develop sustainable and cost-effective mining equipment and high-efficiency mining technologies, benefiting the nation's manufacturing and mining sectors and significantly enhancing the competitiveness of the Australian mining industry.Read moreRead less
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
Pharmacology Of Potential Anti-Tumour Agents: Iron Chelators Of The BpT Class
Funder
National Health and Medical Research Council
Funding Amount
$585,455.00
Summary
Pharmacology of Potential Anti-Tumour Agents: Iron Chelators of the BpT Class Cancer cells have a high iron requirement for DNA synthesis and many clinical trials showed Fe chelators are effective anti-cancer drugs. Their potential to act as anti-tumour agents has been confirmed by the entrance of Triapine into widespread NCI clinical trials. In this NHMRC Renewal, we will perform pharmacological and preclinical studies to promote the development of BpT chelators as novel anti-tumour agents.
The early evolution of the Earth system from multiple sulfur isotope records of sediments and seafloor mineral systems. This project addresses the early evolution of the Earth system that is one of the most important questions in Earth Sciences. It will use Australia's unique rock record and analytical techniques developed in Australia in collaboration with leading international researchers. The National Research Priority area 'An environmentally sustainable Australia: developing deep Earth reso ....The early evolution of the Earth system from multiple sulfur isotope records of sediments and seafloor mineral systems. This project addresses the early evolution of the Earth system that is one of the most important questions in Earth Sciences. It will use Australia's unique rock record and analytical techniques developed in Australia in collaboration with leading international researchers. The National Research Priority area 'An environmentally sustainable Australia: developing deep Earth resources' will benefit through the development of better exploration models for Archaean submarine metal deposits. Students will obtain a high level understanding of the early Earth system, ore deposits, stable isotope and transition metal geochemistry, which are directly applicable in both pure and applied research and mineral exploration.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0230569
Funder
Australian Research Council
Funding Amount
$175,000.00
Summary
INTEGRATED PARTICLE IMAGE THERMOMETRY / VELOCIMETRY FACILITY. This proposal seeks to establish a specialised Particle Image Thermometry / Velocimetry (PITV) facility for simultaneous three-dimensional measurements of global temperature and velocity fields in complex flows. The proposed facility is needed to obtain experimental validations for theories and models developed for complex reacting and non-reacting flows that are strongly influenced by transient behaviour. Applications of PITV include ....INTEGRATED PARTICLE IMAGE THERMOMETRY / VELOCIMETRY FACILITY. This proposal seeks to establish a specialised Particle Image Thermometry / Velocimetry (PITV) facility for simultaneous three-dimensional measurements of global temperature and velocity fields in complex flows. The proposed facility is needed to obtain experimental validations for theories and models developed for complex reacting and non-reacting flows that are strongly influenced by transient behaviour. Applications of PITV include, but are not limited to, low-temperature reacting flows, mixing, jets, wakes, shear layers, time-dependent multiphase flows, unsteady turbulent flows, complex rotating machinery and other periodic flows, as well as natural convection studies.Read moreRead less
Low emission iron and steelmaking using hydrogen to pre-reduce lump ore. This project aims to develop and apply a new route of lump iron ore pre-reduction with hydrogen or H2-enriched gases for ironmaking to minimise CO2 emission from steel production. The route will be built up on the base of H2 reduction kinetics of iron ore and with novel technologies such as CO2 recycle and H2-heating using hot blast, underpinning the hydrogen economy by addressing the environmental concerns in mineral and s ....Low emission iron and steelmaking using hydrogen to pre-reduce lump ore. This project aims to develop and apply a new route of lump iron ore pre-reduction with hydrogen or H2-enriched gases for ironmaking to minimise CO2 emission from steel production. The route will be built up on the base of H2 reduction kinetics of iron ore and with novel technologies such as CO2 recycle and H2-heating using hot blast, underpinning the hydrogen economy by addressing the environmental concerns in mineral and steel industries. It is not only significant for low-carbon steel production, but also for better fundamental understanding to develop the future zero-emission iron and steelmaking with hydrogen. The project will be very beneficent because it increases the use of lump iron ore and expends Australian export of iron ores.Read moreRead less
ARC Centre of Excellence for Enabling Eco-Efficient Beneficiation of Minerals. The aim of the Centre is to progress scientific knowledge to establish transformational improvement in minerals beneficiation, essential for meeting global demand for metals. The research aims to achieve more selective, faster, and efficient separations, combining major advances in separation technologies with increased functionality of new reagents. The Centre outcomes will also ensure the sustainability of the miner ....ARC Centre of Excellence for Enabling Eco-Efficient Beneficiation of Minerals. The aim of the Centre is to progress scientific knowledge to establish transformational improvement in minerals beneficiation, essential for meeting global demand for metals. The research aims to achieve more selective, faster, and efficient separations, combining major advances in separation technologies with increased functionality of new reagents. The Centre outcomes will also ensure the sustainability of the minerals industry in Australia, through a significant reduction in cost, environmental impact, and through lower energy and water usage. The Centre also seeks to establish a new generation of scientists and research leaders in minerals beneficiation to support the innovation needed into the future by this major Australian industry.Read moreRead less
Four dimensional lithospheric evolution and controls on mineral system distribution in Neoarchean to Paleoproterozoic terranes. This project will resolve important questions about the links between the evolution and preservation of continents and important mineral deposits in Australia and West Africa between 2.7 and 1.8 billion years ago. The results will improve the understanding of a key period of Earth history and make a major contribution to mineral exploration.