Inhibition Of IFN-?/? By Human Metapneumovirus And The Induction Of Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$605,251.00
Summary
The newly isolated human metapneumovirus (hMPV) causes significant respiratory illness in infants, young children and the elderly. The virus can persist long-term and may predispose individuals to chronic lung disease. This proposal aims to determine the mechanisms by which hMPV infection causes respiratory disease, with a view to improving treatments and preventing disease.
Clinical Review Of A Cohort Aged 22-33 Years Conceived Using Assisted Reproductive Technologies
Funder
National Health and Medical Research Council
Funding Amount
$946,454.00
Summary
In a recent study, using telephone-interviews, we compared the health and wellbeing of 547 singleton young adults born following assisted reproductive technologies (ART), with 549 matched controls. Reviewing their health when they are 22-33 years is possible because of their ongoing interest. We have a protocol in place to measure their cardiac and respiratory function and other aspects of growth and development. Our findings will fill a major knowledge gap about the longer term safety of ART.
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
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.
AusDiab 3: Emerging Risk Factors For And Long-term Incidence Of Cardio-metabolic Diseases
Funder
National Health and Medical Research Council
Funding Amount
$2,616,397.00
Summary
This study will track 11,000 Australian adults over 12 years to determine how many develop diabetes, obesity, kidney and heart disease. The study will develop ways to best predict those who are going to develop these conditions before they have arisen, and will explore a range of novel risk factors to better understand these conditions.
Assessing Infrastructure And Contextual Factors In Relation To Cardiometabolic Outcomes In Remote Indigenous Communities: Evidence For Policy Change
Funder
National Health and Medical Research Council
Funding Amount
$1,113,005.00
Summary
Cardiometabolic diseases account for the major burden of morbidity and mortality for Indigenous populations. This study with 75 remote Indigenous communities will be the first to evaluate features of their social, built and physical environments in relation to cardiometabolic risks and diseases. Policy-relevant results will identify features of environments to be targeted to reduce chronic diseases for Indigenous peoples in remote communities.
The Role Of Capsid Protein Nucleolar Localisation In Chikungunya Virus: Implications For Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Chikungunya virus (CHIKV) is a globally widespread mosquito-borne alphavirus capable of causing considerable human morbidity and mortality. With no CHIKV vaccine or antiviral available this proposal aims to develop a live attenuated CHIKV vaccine, rationally designed by investigating the host cell nucleolar trafficking of CHIKV capsid protein. This vaccine has the potential to provide cross-protection against additional arthritogenic alphaviruses endemic to Australia such as Ross River virus.
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.
Mitochondrial Iron Overload And Friedreich's Ataxia: The Role Of Frataxin In Iron And Haem Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$285,990.00
Summary
Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. Recent studies using Baker's yeast have shown that the deletion of frataxin results in the accumulation of toxic iron in the mitochondrion. More recently, a variety of studies have shown that FA patients have iron loading within their cells. The iron build-up may cause severe damage. At present, the role of frataxin in mammalian mitochondrial iron metabolism is unknown. Our preliminary studies demonstrate that frataxin i ....Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. Recent studies using Baker's yeast have shown that the deletion of frataxin results in the accumulation of toxic iron in the mitochondrion. More recently, a variety of studies have shown that FA patients have iron loading within their cells. The iron build-up may cause severe damage. At present, the role of frataxin in mammalian mitochondrial iron metabolism is unknown. Our preliminary studies demonstrate that frataxin is down-regulated by either erythroid differentiation or the haem precursor protoporphyrin IX (Becker and Richardson, submitted). These data strongly suggest a role for frataxin in iron metabolism. In the present study we will continue to assess if frataxin plays a role in the way cells handle iron. Using a unique model of mitochondrial iron overload developed in my lab (Richardson et al. (1996) BLOOD 87:3477), we will extensively investigate the iron metabolism of the mitochondrion in order to determine the function of frataxin and its role in Friedreich's ataxia. In addition, we have developed a series of new drugs known as iron chelators that can enter the mitochondrion due to their high lipid solubility (Becker and Richardson 1999 J. Lab. Clin. Med. 134:510). These latter drugs are far more effective than the chelator currently used to treat iron overload, desferrioxamine (DFO). Indeed, our chelators have been designed to result in high iron chelation efficacy but low toxicity (see Becker and Richardson, 1999). This exciting research may be crucial in understanding the development of FA and in creating new therapies such as the use of iron chelators.Read moreRead less
Mitochondrial Iron Overload And Friedreich's Ataxia: The Role Of Frataxin In Iron And Haem Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$606,000.00
Summary
Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. A variety of studies using Baker's yeast and conditional frataxin knockout (KO) mice have shown that deletion of frataxin leads to the accumulation of toxic iron in their mitochondrion. More recently, a variety of studies have shown that FA patients have iron-loading within their mitochondrion. Iron in the highly redox active environment of the mitochondrion could contribute to the generation of cytotoxic radicals that c ....Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. A variety of studies using Baker's yeast and conditional frataxin knockout (KO) mice have shown that deletion of frataxin leads to the accumulation of toxic iron in their mitochondrion. More recently, a variety of studies have shown that FA patients have iron-loading within their mitochondrion. Iron in the highly redox active environment of the mitochondrion could contribute to the generation of cytotoxic radicals that cause severe damage. Further, cells deficient in frataxin are sensitive to oxidant stress and Fe chelators rescue oxidant-mediated death of cells from FA patients. Indeed, free radical scavengers have shown to be of use in the treatment of this disease. Studies in DR's lab during this NHMRC grant have shown that frataxin is down-regulated by erythroid differentiation or the haem precursor, protoporphyrin IX (BLOOD 2002;99:3813-22). These data indicate a role for frataxin in Fe metabolism and the pathogenesis of FA. In this study we will continue to examine the role of frataxin in the way cells handle Fe using experimental models developed under the current NHMRC grant. These include transfected cell lines with low frataxin expression generated using an expression vector containing anti-sense frataxin cDNA. Further we obtained the frataxin conditional KO mouse and generated a breeding colony. These animals display many of the pathological features of FA and are the best current model of the disease. Indeed, they will be critical for assessing the role of frataxin in Fe metabolism and as a model to test the ability of Fe-binding drugs to prevent the pathology observed. We designed lipid-soluble chelators that can enter the mitochondrion to bind Fe (Biochim Biophys Acta 2001;1536:133-140) and these ligands will be tested to prevent disease progression in the KO mice. This exciting research is crucial for understanding the pathogenesis of FA and in creating new therapies.Read moreRead less