Novel Insights Into The Pathobiology Of Alphavirus Infections
Funder
National Health and Medical Research Council
Funding Amount
$827,660.00
Summary
Infections with mosquito-borne viruses are increasing at an alarming rate worldwide. Ross River virus is endemic in parts of Australia, PNG and Pacific islands, while chikungunya virus is distributed globally and causes recurrent pandemics that involve millions of people. These viruses cause severe musculoskeletal disease for several months after infection. This project aims to establish how these viruses interact with the human host to cause disease and may provide a basis for new treatments.
Centre Of Research Excellence On Sitting Time And Chronic Disease Prevention – Mechanisms, Measurement And Interventions
Funder
National Health and Medical Research Council
Funding Amount
$2,657,874.00
Summary
Australian research has identified serious health consequences arising from the 7 to 10 hours of daily sitting that most people do, especially in relation to ‘diseases of inactivity’ – type 2 diabetes, coronary heart disease and breast and colon cancer – that are an unwelcome burden on individuals, families and health systems. This new research examines the practical feasibility and the preventive-health benefits of changing children’s and adults’ sitting time in schools, workplaces and the home ....Australian research has identified serious health consequences arising from the 7 to 10 hours of daily sitting that most people do, especially in relation to ‘diseases of inactivity’ – type 2 diabetes, coronary heart disease and breast and colon cancer – that are an unwelcome burden on individuals, families and health systems. This new research examines the practical feasibility and the preventive-health benefits of changing children’s and adults’ sitting time in schools, workplaces and the home environment.Read moreRead less
Understanding And Overcoming Cardiovascular And Diabetes Inequalities In Indigenous Australians
Funder
National Health and Medical Research Council
Funding Amount
$707,370.00
Summary
Aboriginal and Torres Strait Islanders experience the highest rates of heart disease and diabetes of all Australians. The reasons for this large disparity is not yet fully understood. I propose to investigate the patterns, causes, complications and links between heart disease and diabetes in Indigenous populations to identify better ways of managing and preventing chronic disease in high risk communities.
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
Reducing Prolonged Workplace Sitting Time In Office Workers: A Cluster-randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$524,613.00
Summary
Groundbreaking Australian research shows that sitting for too long, which is routine for most office workers, contributes to overweight and to a greater risk of developing diabetes and heart disease. In over 300 desk-bound office workers, this world-first study will assess the effectiveness of an innovative workplace program aimed at reducing and breaking up sitting time. It will identify practical ways for Australian office workers to minimise unhealthy effects of sitting too much at work.
Role Of Transition Metal Ions And Redox Activity In The Development Of Atherosclerotic Plaques
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability ....Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability to generate free radicals is controversial. This study will employ a novel, minimally-invasive, technique to assess the nature and quantity of metal ions present in well-defined human and animal lesions at different stages of lesion development. The ability of these metal ions to catalyse free radical formation from components present in the artery wall will also be assessed. The release of these metal ions from the artery wall to added organic molecules will be assessed as this might minimise their potential to cause damage, and provide a possible therapeutic strategy. These studies will therefore provide valuable information as to the significance and role of reactive metal ions in the development of human artery disease and the possible prevention, or minimisation, of such processes.Read moreRead less