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
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
Ecosystem resilience of Shark Bay under changing ocean climate. This project aims to investigate the resilience of the Shark Bay World Heritage Site to projected climate change. This project will generate new knowledge for marine conservation through analyses of habitat loss on nutrient budgets and productivity in seagrass and microbialite ecosystems. Expected outcomes are an improved understanding of climate-driven shifts on ecosystem processes in Shark Bay, incorporating science-based evidence ....Ecosystem resilience of Shark Bay under changing ocean climate. This project aims to investigate the resilience of the Shark Bay World Heritage Site to projected climate change. This project will generate new knowledge for marine conservation through analyses of habitat loss on nutrient budgets and productivity in seagrass and microbialite ecosystems. Expected outcomes are an improved understanding of climate-driven shifts on ecosystem processes in Shark Bay, incorporating science-based evidence for better conservation and management. This will provide significant benefits by contributing to the future-proofing of Shark Bay’s World Heritage values to climate change, and more broadly by demonstrating the consequences of the continued tropicalisation of Australia’s coastline.Read moreRead less
Utilising plant-sediment-feedbacks to enhance seagrass restoration. This project aims to investigate the role of sediment microbes in promoting the health of threatened seagrass species across Australia. This project expects to create new knowledge for enhancing restoration success for seagrasses by integrating macro and micro-ecology, environmental genomics, plant ecology and ecosystem function (e.g. nutrient and biogeochemistry cycling). Expected outcomes are new knowledge to enhance seagrass ....Utilising plant-sediment-feedbacks to enhance seagrass restoration. This project aims to investigate the role of sediment microbes in promoting the health of threatened seagrass species across Australia. This project expects to create new knowledge for enhancing restoration success for seagrasses by integrating macro and micro-ecology, environmental genomics, plant ecology and ecosystem function (e.g. nutrient and biogeochemistry cycling). Expected outcomes are new knowledge to enhance seagrass restoration utilising sediment microbes that can be integrated into management and policy. This project should provide significant benefits, such as the development of key strategic alliances to enhance management of seagrasses, and the ecosystem services, and economic and social benefits they provide.Read moreRead less
Unravelling the cycling of nitrogen along a subtropical freshwater-marine continuum using a multi-isotope, multi-tracer and modelling approach. This project will significantly advance our understanding of the sources, cycling and pathways of nitrogen along a sub-tropical catchment-river-estuary. As such, the findings from this research will have direct implications to the management, rehabilitation and protection of waterways (including biodiversity) in Australia.
Quantitative metrics for determining aquifer ecosystem state. Clean groundwater comes from dirty surface water by way of biological purification. This project will develop quantitative ways to assess groundwater ecosystems to ensure the sustainable extraction of water and maintenance of these crucial ecosystems.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100035
Funder
Australian Research Council
Funding Amount
$1,205,137.00
Summary
Founding an Australian Critical Zone Observatory Network. This proposal founds a new network of Australian Critical Zone Observatories. The network will fill essential knowledge gaps about interactions of under- and above-ground environmental processes and their responses to disturbance and change. These interactions determine the sustainability of food, clean water, mineral resources and Australian ecosystems, and cannot be studied with existing environmental infrastructure. The 5 foundation ....Founding an Australian Critical Zone Observatory Network. This proposal founds a new network of Australian Critical Zone Observatories. The network will fill essential knowledge gaps about interactions of under- and above-ground environmental processes and their responses to disturbance and change. These interactions determine the sustainability of food, clean water, mineral resources and Australian ecosystems, and cannot be studied with existing environmental infrastructure. The 5 foundational sites will host integrated monitoring equipment to observe stocks and fluxes of carbon, water, energy and mass across the “Critical Zone” – the vertical span from plant canopies to fresh bedrock. Joining a burgeoning international movement, the network will catalyse Critical Zone science in Australia.Read moreRead less