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.
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
Data-driven monitoring of raceway dynamics in ironmaking blast furnaces. Raceway dynamics in ironmaking blast furnaces affect operational stability and cost considerably, yet their dynamic behaviour has not been well monitored online. The project aims to develop a data-driven model for monitoring the internal state of gas-solid-powder reacting flow in the raceway and predicting raceway anomalies online. It will be achieved by combining particle-fluid numerical simulations with data processing an ....Data-driven monitoring of raceway dynamics in ironmaking blast furnaces. Raceway dynamics in ironmaking blast furnaces affect operational stability and cost considerably, yet their dynamic behaviour has not been well monitored online. The project aims to develop a data-driven model for monitoring the internal state of gas-solid-powder reacting flow in the raceway and predicting raceway anomalies online. It will be achieved by combining particle-fluid numerical simulations with data processing and reduced-order state observer, supported by lab/plant experiments, and collaborating with two industry partners from coal and steel industries. The project outcomes including codes, models and raceway control strategies can help promote Australian metallurgical coal's global markets and ultimately the Australian economy.Read moreRead less
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
A novel low-energy process route for primary copper production utilising synergistic hydro- and pyro-metallurgical processes. With increasing demand for copper metal, there is an urgent need to find new ways to efficiently treat lower grade ores. The new process offers a way of significantly reducing energy consumption and greenhouse gas emissions in primary copper production and making more efficient use of the world's copper resources.
Modelling of particle-fluid reactive flows coupled with phase changes. This project aims to develop an integrated mathematical model for reliably describing multiphase reactive flow coupled with phase change. Particle-fluid reactive flows with phase changes are widely encountered in many energy-intensive industries, yet process design and optimization are hindered by the lack of understanding of complex phenomena governing particularly multiphase flow, phase change and their interactions. The m ....Modelling of particle-fluid reactive flows coupled with phase changes. This project aims to develop an integrated mathematical model for reliably describing multiphase reactive flow coupled with phase change. Particle-fluid reactive flows with phase changes are widely encountered in many energy-intensive industries, yet process design and optimization are hindered by the lack of understanding of complex phenomena governing particularly multiphase flow, phase change and their interactions. The model will be achieved by means of combining advanced particle-scale numerical techniques with pre-database-based thermodynamic model, supported by physical experiments. The outcomes will be applied across a range of industries of vital importance to Australian economic and technological future. It will help transform Australian pyrometallurgy and chemical industries, open new markets for a range of Australian minerals like low-grade coal and iron/copper ore, and ultimately enhance competitiveness of Australian economy.Read moreRead less