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
Industrial Transformation Research Hubs - Grant ID: IH130200012
Funder
Australian Research Council
Funding Amount
$2,748,358.00
Summary
ARC Research Hub for Basin GEodyNamics and Evolution of SedImentary Systems (GENESIS). ARC Research Hub for Basin GEodyNamics and Evolution of SedImentary Systems (GENESIS). This Research Hub aims to undertake simultaneous modelling of deep Earth and surface processes, spanning basin scales to individual sediment grains. The Hub will develop and apply cutting-edge basin simulation approaches to transform the seeding and testing of basin exploration models, extending their viability to complex, ....ARC Research Hub for Basin GEodyNamics and Evolution of SedImentary Systems (GENESIS). ARC Research Hub for Basin GEodyNamics and Evolution of SedImentary Systems (GENESIS). This Research Hub aims to undertake simultaneous modelling of deep Earth and surface processes, spanning basin scales to individual sediment grains. The Hub will develop and apply cutting-edge basin simulation approaches to transform the seeding and testing of basin exploration models, extending their viability to complex, inaccessible remote and deep exploration targets. The Hub will fuse multidimensional data into five dimensional basin models (space and time, with uncertainty estimates) by coupling the evolution of mantle flow, crustal deformation, erosion and sedimentary processes, achieving a quantum leap in basin modelling and petroleum systems analysis.Read moreRead less
A National Population-based Study Of Rheumatic Heart Disease In Pregnancy
Funder
National Health and Medical Research Council
Funding Amount
$877,826.00
Summary
Whilst overall a rare disease, Indigenous peoples have disproportionately high rates of rheumatic heart disease (RHD). This study explores the prevalence and distribution of RHD in pregnancy in Australia and New Zealand. It details current management, diagnostic and referral process and risk factors. Key attributes of culturally safe models of care for RHD in pregnancy are explored, particularly as they relate to Indigenous women. Findings will inform policy, guidelines and education resources.
Special Research Initiatives - Grant ID: SR0354575
Funder
Australian Research Council
Funding Amount
$30,000.00
Summary
Earth and Ocean Informatics and Technology Network (EON-ITnet). Sustainable resource exploration and mining onshore, as well as marine planning, exploration, and defence depend on effective cross-disciplinary investigation, sharing of expertise and technologies for integration and computational analysis of multidimensional data spaces. EON-ITNET will cross-fertilise the use of artificial intelligence, advanced computing and smart information sharing for management, analysis, visualisation and me ....Earth and Ocean Informatics and Technology Network (EON-ITnet). Sustainable resource exploration and mining onshore, as well as marine planning, exploration, and defence depend on effective cross-disciplinary investigation, sharing of expertise and technologies for integration and computational analysis of multidimensional data spaces. EON-ITNET will cross-fertilise the use of artificial intelligence, advanced computing and smart information sharing for management, analysis, visualisation and metadata modelling between these traditionally separate research groups, with the outcome of improving research efficiency and lowering costs. EON-ITNET will form an alliance with the Caltech-based GeoFramework, which is advancing a novel object-oriented data analysis environment, binding community software for Earth visualisation and simulation to 4D data bases.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0346878
Funder
Australian Research Council
Funding Amount
$190,000.00
Summary
GeoWulf: An Inference Engine for Complex Earth Systems. The project is to build a `Beowulf' cluster as a platform for solving
complex data inference problems in the Earth sciences, and in
particular the fields of thermochronology, seismology, crustal and
mantle dynamics, and landform evolution. A Beowulf cluster is a
network-linked set of commonly available `off-the-shelf' PC-computers
configured to give unprecedented performance/cost ratio. Projects
using the Beowulf facility will combine ....GeoWulf: An Inference Engine for Complex Earth Systems. The project is to build a `Beowulf' cluster as a platform for solving
complex data inference problems in the Earth sciences, and in
particular the fields of thermochronology, seismology, crustal and
mantle dynamics, and landform evolution. A Beowulf cluster is a
network-linked set of commonly available `off-the-shelf' PC-computers
configured to give unprecedented performance/cost ratio. Projects
using the Beowulf facility will combine state-of-the-art computational
techniques recently developed at ANU, and high quality data sets
collected over the past decade to address fundamental questions in
the Geosciences.Read moreRead less
Development Of Iron Chelators For The Treatment Of Friedreichs Ataxia And The Role Of Frataxin In Iron Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$550,987.00
Summary
Friedreich's ataxia (FA) is a neuro- and cardio-degenerative disease where there is an accumulation of toxic Fe in the mitochondrion. Excitingly, work from our current NHMRC grant showed iron plays a significant role in FA pathology. Importantly, we developed new drugs (Fe chelators) which rescue the cardiac pathology of FA in an animal model. Studies will now assess if our drugs prevent the neurodegeneration of FA in another animal model. This work could lead to novel therapies for FA.
ARC Financial Integrity Research Network. The integrity of the financial system is constantly under stress because of the development of ever more complex financial instruments, structures and strategies, and the associated research technologies that continues to accelerate worldwide. FIRN's vision is to harness the considerable strengths of Australia's internationally renowned finance, accounting and economics researchers into a research agenda to address issues concerning the integrity of the ....ARC Financial Integrity Research Network. The integrity of the financial system is constantly under stress because of the development of ever more complex financial instruments, structures and strategies, and the associated research technologies that continues to accelerate worldwide. FIRN's vision is to harness the considerable strengths of Australia's internationally renowned finance, accounting and economics researchers into a research agenda to address issues concerning the integrity of the financial system. It will enable Australian research in this area to match the scale and impact of similar research in other major international financial centres, and play an essential role in placing Australia among the world's leaders in financial markets related research.Read moreRead less