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.
Developing A Prototype Of A Next Generation Brain Computer Interface
Funder
National Health and Medical Research Council
Funding Amount
$837,398.00
Summary
Persons affected by quadriplegia and hemiplegia from stroke and spinal cord injury have few treatment options. Brain Machine Interfaces reconnect brain to a prosthetic limb, bypassing damaged nervous system. Our group has developed a BMI that can be implanted minimally-invasively, inside a blood vessel in the brain. We propose to manufacture a world-first device for a human clinical trial pilot study. The aim is to restore mechanical control over the physical environment for a paralysed patient.
Sleep loss and disordered sleep is now recognised as contributing to mortality, chronic disease and economic health burden. The CCRE in Interdisciplinary Sleep Health (CRISH) aims to investigate the biology of sleep, and to prevent and to treat disorders of sleep through a uniquely interdisciplinary approach. The centre will support world-class interventional research aimed to inform clinical practice and alter health policy. The next generation of sleep researchers will be fostered through nati ....Sleep loss and disordered sleep is now recognised as contributing to mortality, chronic disease and economic health burden. The CCRE in Interdisciplinary Sleep Health (CRISH) aims to investigate the biology of sleep, and to prevent and to treat disorders of sleep through a uniquely interdisciplinary approach. The centre will support world-class interventional research aimed to inform clinical practice and alter health policy. The next generation of sleep researchers will be fostered through national and international collaborations.Read moreRead less
Targeting PI3K-regulated Small Non-coding RNAs To Restore Cardiac Function
Funder
National Health and Medical Research Council
Funding Amount
$610,204.00
Summary
Heart failure affects approximately 2.4% of the adult population and over 11% of people over 80 years old. The majority of existing therapies slow, rather than reverse heart failure progression. The primary goal of this study is to determine whether regulating novel regulatory genes can enhance cardiac function in a setting of heart failure. Ultimately, technologies that target these genes may lead to innovative pharmacotherapies in the clinical management of heart failure.
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
Shallow water carbonate sediment dissolution in the global carbon cycle. Carbonate sediment dissolution is a globally significant process, but poorly understood in shallow marine waters. This project will determine whether the combined effect of organic matter, ocean acidification and pore water flow in shallow water carbonate sediments increases the release of calcium and alkalinity to the ocean. This project is significant because this release has not previously been accounted for and may lead ....Shallow water carbonate sediment dissolution in the global carbon cycle. Carbonate sediment dissolution is a globally significant process, but poorly understood in shallow marine waters. This project will determine whether the combined effect of organic matter, ocean acidification and pore water flow in shallow water carbonate sediments increases the release of calcium and alkalinity to the ocean. This project is significant because this release has not previously been accounted for and may lead to an additional uptake of atmospheric carbon dioxide into the global ocean, maybe some additional buffering against ocean acidification, but unfortunately, maybe also a loss of carbonate ecosystems. The outcomes of this project will make a significant contribution to our understanding of the global carbon cycle.
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Can eco-evolutionary theories explain outcomes of microbiome coalescence . Environmental microbial communities are among the most abundant and diverse natural communities, responsible for many ecologically and economically important ecosystem functions, including primary productivity and climate regulation. This project aims to identify the biotic and abiotic factors that regulate community and functional outcomes of microbiome coalescence (the mixing of two different communities) caused by natu ....Can eco-evolutionary theories explain outcomes of microbiome coalescence . Environmental microbial communities are among the most abundant and diverse natural communities, responsible for many ecologically and economically important ecosystem functions, including primary productivity and climate regulation. This project aims to identify the biotic and abiotic factors that regulate community and functional outcomes of microbiome coalescence (the mixing of two different communities) caused by natural and anthropogenic activities. The outcomes will provide a unifying ecological framework to predict variation in microbiomes across different scales, ecosystem types and disturbances, and will generate critical knowledge for the development of effective microbiome products, a rapidly growing industryRead moreRead less
The Structural Basis For Glutamate Transporter Function
Funder
National Health and Medical Research Council
Funding Amount
$373,144.00
Summary
Glutamate transporters are vacuum cleaners in the brain that suck the neurotransmitter glutamate into cells. When the glutamate vacuum breaks down or becomes blocked, glutamate levels outside cells increase, leading to cell death in the brain. This process underlies the damage in many brain diseases including Alzheimer’s disease and stroke. The aim of this project is to understand the mechanism of the glutamate vacuum cleaner so we can develop therapeutics to fix it when it breaks down.