Climate Change And Rural Communities: Integrated Study Of Physical And Social Impacts, Health Risks And Adaptive Options
Funder
National Health and Medical Research Council
Funding Amount
$611,599.00
Summary
Rural Australia has begun to experience climate change impacts - which will increase in future. Losses in farm yields, water supplies, property, community morale and family incomes have diverse health effects. We will study the separate and joint effects of climate change and associated extreme events (e.g., bushfires) on selected health outcomes. Using integrative methods, we will clarify the main influences on health risks, their future projections, and how best to intervene to lessen risks.
The Role And Inheritance Of Constitutional Epimutations In Early-onset Colorectal Cancer.
Funder
National Health and Medical Research Council
Funding Amount
$347,551.00
Summary
Traditionally familial cancers are thought to be caused by spelling mistakes within the genetic code of cancer prevention genes. Our group has found that chemical attachments to one gene (MLH1) stops it working, even where there is no spelling mistake, and that those chemical changes can be inherited in families with bowel cancer. We will determine how frequently this type of defect occurs in bowel cancer patients, how and why it arises, and if other cancer genes are similarly affected.
Quit In General Practice: A Cluster Randomised Trial Of Enhanced In-practice Support For Smoking Cessation
Funder
National Health and Medical Research Council
Funding Amount
$1,117,241.00
Summary
Tobacco smoking remains the most common preventable cause of death and illness in Australia today. Smoking cessation programs are some of the most effective and cost effective strategies that can be undertaken in health care settings, including general practice. This project will test a new approach to supporting smoking cessation in general practice. This involves the practice nurse, GP and Quitline working in partnership to provide a flexible program of suport to meet the needs of smokers.
A NOVEL MOUSE MODEL TO INVESTIGATE THE MECHANISMS OF VIRUS-INDUCED ARTHRITIS
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators ( ....We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators (cytokines-chemokines) and antibodies is an overwhelming positive aspect of our physiological response to infection by microbes. Protection from disease by these immune compounds can happen naturally, or the body's ability to produce these factors can be exploited to our benefit via the administration of vaccines. However, these factors can also be detrimental to the host contributing to severe disease. For instance, work performed almost 40 years ago showed for the first time that under particular conditions, antibodies against viruses can enhance infection, instead of inhibiting infection as normally seen. In the intervening years work by scientists all over the world has associated antibody-dependent enhancement (ADE) of infection to many types of viruses; ADE is even thought to be a risk factor to serious disease with dengue virus, and has been shown in vitro for the AIDS virus and Ebola virus. We have recently discovered a molecular mechanism which explains how antibody enhances viral infection in vitro. In studies on immune cells infected with Ross River Virus (RRV) we found that infection helped by antibody resulted in the specific disruption to the production of cellular chemicals which are toxic to viruses. Are these mechanisms of antibody-enhanced infection also found in animals? Will such mode of infection cause enhanced disease and tissue pathology (arthritis) in animals?Read moreRead less
Thai Health-Risk Transition: A National Cohort Study - Phase II
Funder
National Health and Medical Research Council
Funding Amount
$1,662,829.00
Summary
We are conducting a pioneering collaborative longitudinal study of population health in Thailand, following over time more than 80,000 adults living throughout the country. We repeatedly measure a wide array of health risks and outcomes. We capture information on the health-risk transition underway in Thailand as the population experiences the new burden of disease associated with economic development and modernisation. We team up with policy makers for national responses to lower the burden.
Chronic Disease Outcomes And Enhanced Primary Care In Seniors: A Cross-Jurisdictional Linkage Project
Funder
National Health and Medical Research Council
Funding Amount
$1,077,766.00
Summary
This project will provide evidence on how best to use the efforts of Australian GPs to obtain better outcomes in patients aged 65+ years who suffer from chronic diseases such as diabetes, heart disease and high blood pressure, asthma and emphysema, seizures and stomach disorders. It will also examine the best way that GP visits can promote healthier ageing in all older seniors, aged 75+ years. For each disease and in older seniors, the study will be able to detect which of the following factors ....This project will provide evidence on how best to use the efforts of Australian GPs to obtain better outcomes in patients aged 65+ years who suffer from chronic diseases such as diabetes, heart disease and high blood pressure, asthma and emphysema, seizures and stomach disorders. It will also examine the best way that GP visits can promote healthier ageing in all older seniors, aged 75+ years. For each disease and in older seniors, the study will be able to detect which of the following factors are the most important for better patient health: (i) seeing a GP more times, (ii) seeing a GP at more even intervals, (iii) seeing the same GP, or (iv) seeing a GP with a lot of experience in chronic diseases. Separate investigations will be made in older people living in hostels and nursing homes, because their needs may be different. The study will also evaluate the benefits of a major change that occurred to Medicare in 1999, when GPs were paid to perform health assessments and to prepare health plans (with other health workers) for patients with chronic health problems. The results will enable this important initiative to be further improved. The study will use a unique and new Australian research facility, which has brought together health data on the entire population of WA from both the State and Commonwealth levels, including information on Medicare use, pharmaceuticals, hospital stays and deaths. The facility works in such a way as to preserve patient and GP privacy. A strong feature of this research will be the degree of involvement of a representative and voluntary group of older Australian patients who attend GP clinics, and the GPs themselves, in advising the researchers on what's important to consumers and GPs.Read moreRead less
Which Mental Activities And When For Dementia Prevention? The Four Nations Longitudinal Collaboration
Funder
National Health and Medical Research Council
Funding Amount
$183,218.00
Summary
We will examine the link between lifetime participation in complex mental activities and long term dementia risk in a level of detail not previously possible. Four major studies of brain health from around the world will join forces for the first time to determine which mental activities are most closely linked to protection from dementia, and when during the lifespan these are most important. Mental activity will be assessed using our recently published Lifetime of Experiences Questionnaire.
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
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
The Role Of Melanoma Tumour Antigen P97 (Melanotransferrin) In Melanoma Tumourigenesis.
Funder
National Health and Medical Research Council
Funding Amount
$563,242.00
Summary
The Role of Melanoma Tumour Antigen p97 (Melanotransferrin) in Melanoma Tumourigenesis Melanotransferrin (MTf) is a homologue of the iron transport protein, transferrin, and was one of the first well characterised melanoma tumour antigens. Our published studies have shown that MTf plays an important role in melanoma tumourigenesis in vivo. In this proposal, we will assess if it is associated with melanoma progression in patient samples and examine its role in melanoma growth and metastasis.