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.
Changing your mind by changing your brain: An interventionist perspective on cognitive neuroscience. Functional neuroimaging provides a tremendous amount of information about the brain, but what it shows about the mind is less clear. Addressing this fundamental philosophical question requires developing a detailed account of theory-testing in cognitive neuroscience. This project aims to connect neuroimaging to theories of explanation that focus on the way one variable can make a difference to an ....Changing your mind by changing your brain: An interventionist perspective on cognitive neuroscience. Functional neuroimaging provides a tremendous amount of information about the brain, but what it shows about the mind is less clear. Addressing this fundamental philosophical question requires developing a detailed account of theory-testing in cognitive neuroscience. This project aims to connect neuroimaging to theories of explanation that focus on the way one variable can make a difference to another. By linking neuroimaging to facts about manipulable relationships between the brain and the mind, it will also provide a bridge between neuroimaging and complementary technologies for directly intervening on the brain. This, in turn, will provide a platform from which to explore the theoretical and ethical consequences of direct brain manipulation.Read moreRead less
New Polymers for Cellulose-based Bioplastics. We will design new cellulose derivatives by combining carefully engineered synthetic polymers to cellulose. We will explore the fundamental science underpinning the manufacture of these bioplastics, and apply the concept to the design of two new materials, with (super)hydrophobic and antibacterial properties. These materials have the potential to replace synthetic plastics, which comprise one of the major outputs of the chemical industry worldwide. P ....New Polymers for Cellulose-based Bioplastics. We will design new cellulose derivatives by combining carefully engineered synthetic polymers to cellulose. We will explore the fundamental science underpinning the manufacture of these bioplastics, and apply the concept to the design of two new materials, with (super)hydrophobic and antibacterial properties. These materials have the potential to replace synthetic plastics, which comprise one of the major outputs of the chemical industry worldwide. Plastic is present everywhere in human life, but its manufacture and disposal have a strong negative impact on the environment; the new materials manufactured in this project are viable alternatives to plastics, and are sustainable from a production and disposal point of view.Read moreRead less
Living on the edge: how do Australian plants cope with extreme temperature? Of all the climatic factors determining species distributions, temperature is arguably the most important. It is extremes – rather than averages – that drive species evolution. So it is concerning that although extreme temperature events are increasing in frequency and intensity little is known about the breadth of thermal tolerance of plants from extreme environments. This information is crucial to understand species di ....Living on the edge: how do Australian plants cope with extreme temperature? Of all the climatic factors determining species distributions, temperature is arguably the most important. It is extremes – rather than averages – that drive species evolution. So it is concerning that although extreme temperature events are increasing in frequency and intensity little is known about the breadth of thermal tolerance of plants from extreme environments. This information is crucial to understand species distribution and survival under future climate regimes. This project will ascertain the thermal breadth of Australian species growing in situ and under controlled environments. The project will contribute to development of effective conservation, restoration and rehabilitation plans for Australian native plant communities. Read moreRead less
Life, living and livelihoods in satellite cities: new urban forms in India . This project aims to assess the success of satellite cities, conceived as possible solutions to the urgent challenge of rapid urban growth in today’s megacities. Through an ethnography of an Indian satellite city, Mahindra World City, this project aims to generate knowledge on new urban formations and the consequences of experiments in urban development for different socio-economic groups. Understanding the lived experi ....Life, living and livelihoods in satellite cities: new urban forms in India . This project aims to assess the success of satellite cities, conceived as possible solutions to the urgent challenge of rapid urban growth in today’s megacities. Through an ethnography of an Indian satellite city, Mahindra World City, this project aims to generate knowledge on new urban formations and the consequences of experiments in urban development for different socio-economic groups. Understanding the lived experiences of residents/workers in satellite cities aims to form a robust evidence base for research driven dialogue with policy makers, planners and developers. Lessons derived are expected to inform policy and practice as to how to achieve wellbeing for urban residents, while providing indications of Asia’s urban futures.Read moreRead less