A NOVEL MOUSE MODEL TO INVESTIGATE THE MECHANISMS OF VIRUS-INDUCED ARTHRITIS
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators ( ....We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators (cytokines-chemokines) and antibodies is an overwhelming positive aspect of our physiological response to infection by microbes. Protection from disease by these immune compounds can happen naturally, or the body's ability to produce these factors can be exploited to our benefit via the administration of vaccines. However, these factors can also be detrimental to the host contributing to severe disease. For instance, work performed almost 40 years ago showed for the first time that under particular conditions, antibodies against viruses can enhance infection, instead of inhibiting infection as normally seen. In the intervening years work by scientists all over the world has associated antibody-dependent enhancement (ADE) of infection to many types of viruses; ADE is even thought to be a risk factor to serious disease with dengue virus, and has been shown in vitro for the AIDS virus and Ebola virus. We have recently discovered a molecular mechanism which explains how antibody enhances viral infection in vitro. In studies on immune cells infected with Ross River Virus (RRV) we found that infection helped by antibody resulted in the specific disruption to the production of cellular chemicals which are toxic to viruses. Are these mechanisms of antibody-enhanced infection also found in animals? Will such mode of infection cause enhanced disease and tissue pathology (arthritis) in animals?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.
Arbovirus Activation And Modulation Of NLRP3 Inflammasome
Funder
National Health and Medical Research Council
Funding Amount
$779,720.00
Summary
This project aims to establish how mosquito borne viruses such as Ross River and dengue viruses interacts with the human host to cause disease, including how the virus evades the host’s immune response to persist and cause disease for prolonged periods. Knowing how differences in the virus and the host’s immune system interplay to cause asymptomatic to severely disabling disease will assist in devising new treatments and prevention programs to lessen the impact of these diseases in Australia.
GBR as a significant source of climatically relevant aerosol particles. Every cloud drop is formed from a microscopic aerosol particle, known as a cloud condensation nuclei (CCN). In unpolluted environments the CCN particles originate from biogenic sources. Determining the magnitude and driving factors of biogenic aerosol production in different ecosystems is crucial to the development and improvement of climate models. This project aims to determine the mechanisms of new particle production fro ....GBR as a significant source of climatically relevant aerosol particles. Every cloud drop is formed from a microscopic aerosol particle, known as a cloud condensation nuclei (CCN). In unpolluted environments the CCN particles originate from biogenic sources. Determining the magnitude and driving factors of biogenic aerosol production in different ecosystems is crucial to the development and improvement of climate models. This project aims to determine the mechanisms of new particle production from one of the biggest ecosystems in Australia, the Great Barrier Reef. It is expected that the project will establish whether marine aerosol along the Queensland coast is coral-derived and show that this aerosol can affect the CCN concentration and therefore cloud formation and the hydrological cycle.Read moreRead less
The changing relationship between the South Asian and Australian Monsoon in a warming world. The success or failure of the Australian and South Asian Monsoons can mean the difference between prosperity and severe hardship in the affected regions. This project will help to understand the causes of the monsoon variability, both natural and human-induced, and what the future might have in store.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE200100040
Funder
Australian Research Council
Funding Amount
$580,000.00
Summary
Fast Disk Storage to Enable Big Data Science in Weather, Oceans and Climate. This project aims to expand Australia's capacity to do high-impact innovative climate, weather and oceanographic science. Science of this kind relies on massive data coupled to computationally highly intensive and complex analysis. Therefore, the project will purchase fast disk storage and install it at the National Computing Infrastructure. It is anticipated that the project will benefit the nation through better under ....Fast Disk Storage to Enable Big Data Science in Weather, Oceans and Climate. This project aims to expand Australia's capacity to do high-impact innovative climate, weather and oceanographic science. Science of this kind relies on massive data coupled to computationally highly intensive and complex analysis. Therefore, the project will purchase fast disk storage and install it at the National Computing Infrastructure. It is anticipated that the project will benefit the nation through better understanding of the climate system, including extremes; improvements in our capacity to make predictions; and through applications of the science to forecasting, the management of resources among other many other things.Read moreRead less
Remote forcing of Pacific Ocean variability and impacts on global climate. Variability in the Pacific Ocean has a profound impact on global climate. Recent unprecedented decadal variability in the Pacific has been linked to global temperature trends and extremes, yet little is known about what drives this variability or its impact on regional climate. This project will combine observations, advanced coupled climate models and ocean-atmosphere dynamical theory to quantify remote drivers of Pacifi ....Remote forcing of Pacific Ocean variability and impacts on global climate. Variability in the Pacific Ocean has a profound impact on global climate. Recent unprecedented decadal variability in the Pacific has been linked to global temperature trends and extremes, yet little is known about what drives this variability or its impact on regional climate. This project will combine observations, advanced coupled climate models and ocean-atmosphere dynamical theory to quantify remote drivers of Pacific Ocean variability on interannual-decadal time-scales. This project aims to enhance our understanding of the modes of variability operating in this region and their impact on global and Australian climate. This will have significant benefits for the many sectors of society reliant on interseasonal-decadal climate prediction.Read moreRead less
Entrainment and Mixing in Turbulent Negatively Buoyant Jets and Fountains. The project intends to develop tools to accurate predict fountain flows. Volcanic eruptions, building ventilation and brine discharge from desalination plants are all examples of turbulent fountains and negatively buoyant jets. The project aims to conduct an investigation into the turbulent structure of fountains and negatively buoyant jets using numerical simulation and laboratory experiments, and to assess the accuracy ....Entrainment and Mixing in Turbulent Negatively Buoyant Jets and Fountains. The project intends to develop tools to accurate predict fountain flows. Volcanic eruptions, building ventilation and brine discharge from desalination plants are all examples of turbulent fountains and negatively buoyant jets. The project aims to conduct an investigation into the turbulent structure of fountains and negatively buoyant jets using numerical simulation and laboratory experiments, and to assess the accuracy of the commonly used integral models and test the effect of the use of more accurate entrainment relations. This may have a range of applications – enabling better prediction of environmental impacts, reduction of the adverse effects of the discharge of pollutants, and reduction in energy consumption in building ventilation and other industrial applications.Read moreRead less
Thermal stratification, overturning and mixing in riverine environments. Thermal stratification is common in Australia's rivers due to our hot, drought-prone climate and high human demands relative to available supply, which has led to a significant reduction in flows relative to natural levels. Thermal stratification inhibits mixing, creating stagnant conditions characterised by low oxygen levels and increased concentrations of contaminants, leading to algal blooms, fish kills and systemic dama ....Thermal stratification, overturning and mixing in riverine environments. Thermal stratification is common in Australia's rivers due to our hot, drought-prone climate and high human demands relative to available supply, which has led to a significant reduction in flows relative to natural levels. Thermal stratification inhibits mixing, creating stagnant conditions characterised by low oxygen levels and increased concentrations of contaminants, leading to algal blooms, fish kills and systemic damage to ecosystems. The aim of this project is to develop predictive models for the effects of physical processes such as night-time cooling, wind, turbulence and currents on riverine thermal stratification. This is expected to enable a more accurate determination of the flow rates required to maintain the health of our river systems.Read moreRead less
Exploitation of unusual patterns of reactivity of peptides towards radicals. Life depends on free radical reactions of peptides and proteins but, for these compounds to exist, these must be inherently resistant to radicals. This project aims to combine state-of-the-art experiment and theoretical computations to build a detailed picture of peptide and protein radical reactivity, in order to explain this paradox and resolve ambiguities regarding processes through which radical damage to peptides o ....Exploitation of unusual patterns of reactivity of peptides towards radicals. Life depends on free radical reactions of peptides and proteins but, for these compounds to exist, these must be inherently resistant to radicals. This project aims to combine state-of-the-art experiment and theoretical computations to build a detailed picture of peptide and protein radical reactivity, in order to explain this paradox and resolve ambiguities regarding processes through which radical damage to peptides occurs and is repaired. The project also aims to critically evaluate the basic concept of the fidelity of amino acid incorporation during protein biosynthesis. The results of this project could underpin the development of new strategies and therapeutics to treat human diseases, and new materials and synthetic methods to increase the utility of peptides in biotechnology.Read moreRead less