An Australasian, Multi-centre, Randomized, Double-blind, Placebo-controlled Trial Of The Efficacy Of Fluoxetine In Improving Functional Recovery After Acute Stroke
Funder
National Health and Medical Research Council
Funding Amount
$2,306,367.00
Summary
Stroke is one of the top three causes of disability. Treatments that improve recovery after stroke are lacking. We reviewed the world literature and found a number of very small studies which, together, suggest that the antidepressant drug, fluoxetine, may improve the recovery in stroke patients. AFFINITY is a large trial in 1600 Australians and New Zealanders with stroke which aims to find out whether taking fluoxetine for 6 months after a stroke improves recovery compared to a placebo.
Deciphering The Role Of Atypical DNA Methylation In Neuronal Genome Regulation And Neurological Disorders
Funder
National Health and Medical Research Council
Funding Amount
$773,484.00
Summary
This research will use a combination of genomic, biochemical and functional genomics approaches to investigate the role of the atypical mCH form of DNA methylation in neuronal genome regulation and function, and provide new insights into the role of the epigenome in healthy brain function and neural pathologies.
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
The Identification Of Thoracic Targets For Prevention And Intervention In Bronchopulmonary Dysplasia
Funder
National Health and Medical Research Council
Funding Amount
$316,449.00
Summary
The persistence of breathing problems from infancy to later life is a complication of premature birth with lifelong consequences. Breathing problems often occur together with lung disease, but prematurity can also affect heart and blood vessel development, and weakness of the main breathing muscle. We will find out how much the heart, lungs and diaphragm contribute to breathing problems in babies; helping us to better predict, diagnose and treat severe breathing problems in babies born preterm.
Is restoration working? An ecological genetic assessment. This project aims to assess the success of restoration in terms of ecological and genetic viability for plant species in the Fitzgerald River–Stirling Range region of Western Australia, where significant investment is being made in restoring connectivity at a landscape scale. The project intends to compare reproductive output, pollinator behaviour, mating, genetic diversity and pollen dispersal in restored sites with those of undisturbed ....Is restoration working? An ecological genetic assessment. This project aims to assess the success of restoration in terms of ecological and genetic viability for plant species in the Fitzgerald River–Stirling Range region of Western Australia, where significant investment is being made in restoring connectivity at a landscape scale. The project intends to compare reproductive output, pollinator behaviour, mating, genetic diversity and pollen dispersal in restored sites with those of undisturbed natural vegetation. The project moves measures of restoration success beyond that of population establishment and survival to incorporate the evolutionary processes that provide long-term resilience, persistence and functional integration of restored populations into broader landscapes.Read moreRead less
Unravelling the drivers of greenhouse gas emissions in estuaries. The aim of this project is to understand and quantify the factors controlling the emission of carbon dioxide, methane and nitrous oxide from estuaries. Coastal systems play a disproportionately large role in the global emissions of greenhouse gases, but this is poorly quantified. The project plans to use a combination of continuous concentration and stable isotope measurements, process measurements and advanced numerical modelling ....Unravelling the drivers of greenhouse gas emissions in estuaries. The aim of this project is to understand and quantify the factors controlling the emission of carbon dioxide, methane and nitrous oxide from estuaries. Coastal systems play a disproportionately large role in the global emissions of greenhouse gases, but this is poorly quantified. The project plans to use a combination of continuous concentration and stable isotope measurements, process measurements and advanced numerical modelling across a range of undisturbed to disturbed systems. It is intended that this project will provide information for conceptualising, calibrating and verifying models, including green-house gas production. Good models, and the data that support them, such as that provided by this study, are critical for the efficient allocation of management resources in Australian coastal systems, including by our partners. The findings from this project will have direct implications to the management, rehabilitation and protection of waterways (including biodiversity) in Australia.Read moreRead less
Do Exposures Before Conception Influence The Risk Of Asthma In Offspring?
Funder
National Health and Medical Research Council
Funding Amount
$688,586.00
Summary
Asthma and poor lung function are major causes of public health issues. Emerging evidence suggests adverse exposures even before the conception of a child may cause these conditions. The proposed project is part of an international study across generations to identify these factors. This study will provide novel evidence to guide interventions and identify studies to advance this area further. These original findings will be of great importance both nationally and internationally.
Managing evolutionary-ecological process in restoring Banksia woodland resilient to global environmental changes. By manipulating genetic diversity, local selection and gene flow in restored plant communities, this project will establish suitable regimes to manage evolutionary processes in large-scale restoration, thereby improving success and resilience to future changes. It will significantly advance our understanding of evolutionary processes operating in restoration efforts, and lead to impr ....Managing evolutionary-ecological process in restoring Banksia woodland resilient to global environmental changes. By manipulating genetic diversity, local selection and gene flow in restored plant communities, this project will establish suitable regimes to manage evolutionary processes in large-scale restoration, thereby improving success and resilience to future changes. It will significantly advance our understanding of evolutionary processes operating in restoration efforts, and lead to improved restoration success, better long-term ecological functioning in restored ecosystems, better investment of resources, and maintenance of Australia’s biodiversity in the face of rapid environmental change. These findings should be of relevance to broader restoration initiatives managed by the government, community, and industry nationally and internationally.Read moreRead less
Ants, plants, diversity and function: trophic interactions and ecosystem function in a large-scale restoration experiment. Food and clean water are but two of the benefits we reap from functioning ecosystems, but we know little about how individual species contribute to making ecosystems work. This project capitalises on the diversity of Australia's ant fauna by using ants as a model taxon to explore the link between biodiversity and ecosystem functioning.