Optimising Intervention Strategies To Reduce The Burden Of Group A Streptococcus In Aboriginal Communities
Funder
National Health and Medical Research Council
Funding Amount
$856,896.00
Summary
Skin sores are highly prevalent in remote Australian Indigenous communities and can lead to invasive infections and rheumatic heart disease. We will develop mathematical models to understand the transmission of skin sores, allowing us to define the optimal extent (household, community, region), timing and triggers for interventions to interrupt transmission. This will guide public health policy in reducing the prevalence of skin sores and scabies, and their accompanying disease burden.
Optimal management of corrosion and odour problems in sewer systems. Pollutants in wastewater undergo complex changes in sewers, leading to the production and release of odorous and corrosive compounds. Despite major efforts and expenditure by water utilities to mitigate these problems, odorous emissions from sewers are still commonly occurring in urban areas. Furthermore, the value of public assets is significantly diminished due to sewer corrosion, costing hundreds of millions of dollars a yea ....Optimal management of corrosion and odour problems in sewer systems. Pollutants in wastewater undergo complex changes in sewers, leading to the production and release of odorous and corrosive compounds. Despite major efforts and expenditure by water utilities to mitigate these problems, odorous emissions from sewers are still commonly occurring in urban areas. Furthermore, the value of public assets is significantly diminished due to sewer corrosion, costing hundreds of millions of dollars a year in Australia alone. This project is a major joint effort by the Australian water industry and world-leading scientists to generate advanced knowledge and develop effective technologies for optimal odour and corrosion management in sewers, delivering large social, environmental and economic benefits.Read moreRead less
Sewer corrosion reduction through model-supported ventilation control. Ventilation is one of the key technologies for sewer corrosion control. However, its design and operation are currently based on experience and empirical equations, often leading to unsatisfactory results. By integrating in-depth laboratory and pilot-sewer studies under defined conditions with extensive field investigations, this multidisciplinary project aims to develop critical models to predict the corrosion process in res ....Sewer corrosion reduction through model-supported ventilation control. Ventilation is one of the key technologies for sewer corrosion control. However, its design and operation are currently based on experience and empirical equations, often leading to unsatisfactory results. By integrating in-depth laboratory and pilot-sewer studies under defined conditions with extensive field investigations, this multidisciplinary project aims to develop critical models to predict the corrosion process in response to ventilation and dynamic wastewater and atmospheric conditions, enabling model-based sewer ventilation design and operation. The project also aims to deliver novel, field-demonstrated ventilation strategies. The project findings will be incorporated in the Australian ventilation design and operation guidelines.Read moreRead less
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
Unlocking self-healing bio-concrete through multiscale modelling. Self-healing bio-concrete, which uses bacteria as means to repair cracks, has the potential to revolutionise the construction industry and reduce the infrastructure repair and maintenance cost by billions of dollars annually. To unlock this, we need to understand the bacterial self-healing mechanisms for effective control of the performance. This project will develop a multiscale framework to describe the competing mechanisms betw ....Unlocking self-healing bio-concrete through multiscale modelling. Self-healing bio-concrete, which uses bacteria as means to repair cracks, has the potential to revolutionise the construction industry and reduce the infrastructure repair and maintenance cost by billions of dollars annually. To unlock this, we need to understand the bacterial self-healing mechanisms for effective control of the performance. This project will develop a multiscale framework to describe the competing mechanisms between crack widening and healing at the macro-scale, incorporated with key information of substances diffusion and bio-cementation at the meso- and micro-scales. This will enable to optimise the self-healing of bio-concrete via design–test–learn approach and enhance the durability of structures under sustained loads.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.