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
The economics of (mis)information in the age of social media. New media technologies allow anyone to broadcast their views, leading to a “cacophony of voices” where misinformation flourishes. Tools from information economics are tailor-made for understanding information consumption in settings with many biased news sources. We develop economic models where many sources compete to attract and influence heterogenous listeners. We then study how misinformation spreads and amplifies when consumers ....The economics of (mis)information in the age of social media. New media technologies allow anyone to broadcast their views, leading to a “cacophony of voices” where misinformation flourishes. Tools from information economics are tailor-made for understanding information consumption in settings with many biased news sources. We develop economic models where many sources compete to attract and influence heterogenous listeners. We then study how misinformation spreads and amplifies when consumers of information communicate with many others through a social network. Finally, we study how to design simple and robust rules to foster informative discourse and filter misinformation. The results will shape economic policy recommendations for regulating misinformation in media platforms and social media.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.
Using behavioural economic insights to overcome student procrastination. This project aims to study the relations between present-biased time preference, procrastination, and achievement at school, using economic experiments. Investment in human capital generates economic benefits for students, families, employers, and society, but its benefits are realised far into the future. Because of these immediate costs and delayed benefits, behavioural economic theory predicts that students will procrast ....Using behavioural economic insights to overcome student procrastination. This project aims to study the relations between present-biased time preference, procrastination, and achievement at school, using economic experiments. Investment in human capital generates economic benefits for students, families, employers, and society, but its benefits are realised far into the future. Because of these immediate costs and delayed benefits, behavioural economic theory predicts that students will procrastinate. This project will identify the characteristics of students at greatest risk of procrastination, evaluate practical strategies to overcome it, and examine whether it is associated with poorer outcomes. This should help schools and policy makers reduce educational inequalities, and yield long-term benefits over students’ lives.Read moreRead less
Information acquisition and voting behaviour. This project aims to understand citizens’ decisions to acquire information about different policy proposals within a democracy and how such information affects their voting behaviour. Proper democracies rely on the informed participation of their citizens in the political debate and political institutions. The project intends to provide formal theories of information acquisition together with empirical evidence on how voting decisions are shaped by t ....Information acquisition and voting behaviour. This project aims to understand citizens’ decisions to acquire information about different policy proposals within a democracy and how such information affects their voting behaviour. Proper democracies rely on the informed participation of their citizens in the political debate and political institutions. The project intends to provide formal theories of information acquisition together with empirical evidence on how voting decisions are shaped by the quantity and quality of information. Understanding how citizens decide to acquire information would help devise policies to reduce polarisation and improve the quality of the political debate and the democracy.Read moreRead less
Legitimacy and representation: A comprehensive study of electoral systems and strategic voting behaviour. What makes a good electoral system? How can it reflect the preference of the majority while guaranteeing representation to minorities? Should voting be voluntary or mandatory? These are very relevant questions for any democracy, but particularly so for Australia: a country which has always been at the forefront of the electoral debate, that proudly strives to represent with fairness all sect ....Legitimacy and representation: A comprehensive study of electoral systems and strategic voting behaviour. What makes a good electoral system? How can it reflect the preference of the majority while guaranteeing representation to minorities? Should voting be voluntary or mandatory? These are very relevant questions for any democracy, but particularly so for Australia: a country which has always been at the forefront of the electoral debate, that proudly strives to represent with fairness all sectors of its very diverse society and where voting is not only a citizen's right, but also her duty. By approaching these issues in a game theoretic framework, this project proposes to investigate the strategic nature of voting through a comprehensive study of electoral systems. The project will then test our theoretical predictions through a series of laboratory experiments. Read moreRead less
Incentivizing Attendance and Performance at School: A Field Experiment. This project aims to develop and evaluate an incentive-based program to increase the school attendance and performance of Indigenous students to help alleviate current inequalities between Indigenous and non-indigenous Australians. Only 43 per cent of Indigenous Australians graduate from high school compared to 78 per cent for non-Indigenous Australians. The study plans to investigate whether high value rewards (e.g. driving ....Incentivizing Attendance and Performance at School: A Field Experiment. This project aims to develop and evaluate an incentive-based program to increase the school attendance and performance of Indigenous students to help alleviate current inequalities between Indigenous and non-indigenous Australians. Only 43 per cent of Indigenous Australians graduate from high school compared to 78 per cent for non-Indigenous Australians. The study plans to investigate whether high value rewards (e.g. driving licence instruction) are effective in incentivising year 11 and 12 students. It also aims to examine whether the way incentives are provided — ex-post as traditionally done or ex-ante in the form of a trust-based contract — increase high school completion rates of Indigenous students where previous incentive schemes have failed.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100190
Funder
Australian Research Council
Funding Amount
$363,996.00
Summary
Auction design with behavioural bidders. This project aims to incorporate behavioural elements from psychology into the economic analysis of auctions. The project will address discrepancies between traditional economic analysis of auctions based on fully rational bidders, and evidence from psychology and behavioural economics which demonstrates systemic departures from rational decision-making. This will expand realism in economic analysis and contribute new insights for the design of relevant, ....Auction design with behavioural bidders. This project aims to incorporate behavioural elements from psychology into the economic analysis of auctions. The project will address discrepancies between traditional economic analysis of auctions based on fully rational bidders, and evidence from psychology and behavioural economics which demonstrates systemic departures from rational decision-making. This will expand realism in economic analysis and contribute new insights for the design of relevant, real-world auctions such as real-estate auctions or internet auctions. The project outcomes are expected to enhance the efficient allocation of resources, improve our understanding of how different rules affect buyers' well-being and help design fairer auctions.Read moreRead less
The economics of cooperative behaviour. Free-riding and rent-seeking, such as tax avoidance and nepotism, are group-undermining activities that societies including Australia continuously struggle with. The aim of this project is to develop a fuller understanding of how to protect human groups from these socially damaging group-related behaviours. Drawing on a conceptual grounding that combines ideas from across social science, the project aims to implement a suite of economic experiments to deve ....The economics of cooperative behaviour. Free-riding and rent-seeking, such as tax avoidance and nepotism, are group-undermining activities that societies including Australia continuously struggle with. The aim of this project is to develop a fuller understanding of how to protect human groups from these socially damaging group-related behaviours. Drawing on a conceptual grounding that combines ideas from across social science, the project aims to implement a suite of economic experiments to develop a view of humans' cooperative behaviour that unites several strands of economics literature and offers new insights about how institutions that counter free-riding and rent-seeking arise and are maintained.Read moreRead less
The rise of mistrust: Digital platforms and trust in news media. This project aims to investigate how trust and mistrust in news changes audiences’ behaviours as they increasingly access news through digital platforms. Observing the global crisis of trust, the project will undertake a longitudinal analysis of trust and mistrust in news, a four-country experiment that links trust and audience responses, and an in-depth qualitative study that provides specific contexts of these choices. The resear ....The rise of mistrust: Digital platforms and trust in news media. This project aims to investigate how trust and mistrust in news changes audiences’ behaviours as they increasingly access news through digital platforms. Observing the global crisis of trust, the project will undertake a longitudinal analysis of trust and mistrust in news, a four-country experiment that links trust and audience responses, and an in-depth qualitative study that provides specific contexts of these choices. The research will directly benefit policy makers, as it addresses questions of how to better secure trustworthy news content in an age of increasing dominance of digital platforms that algorithmically sort the range of news available to the Australian public.
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