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
Development of Novel Pesticidal Agents. We have discovered a family of naturally occurring plant proteins called the cyclotides that have potent insecticidal activity against Helicoverpa species, one of the major pests on cotton and corn in Australia and world wide. Preliminary evidence has shown that they also have activity against major pests to livestock in Australia, including sheep blowflies. To develop these proteins as potential pesticidal agents it is necessary to understand the struct ....Development of Novel Pesticidal Agents. We have discovered a family of naturally occurring plant proteins called the cyclotides that have potent insecticidal activity against Helicoverpa species, one of the major pests on cotton and corn in Australia and world wide. Preliminary evidence has shown that they also have activity against major pests to livestock in Australia, including sheep blowflies. To develop these proteins as potential pesticidal agents it is necessary to understand the structural basis for their activity. We will do this by chemically synthesising peptides with selected residues mutated to determine their effects on activity.Read moreRead less
Assessment Of Interventions For Controlling Pandemic Influenza And Determining Data Needs To Inform These Assessments
Funder
National Health and Medical Research Council
Funding Amount
$183,040.00
Summary
The aim of this study is to help us prepare for a pandemic of influenza by comparing how effective the various available control strategies are at reducing transmission of the disease. The available control interventions include: reducing the number of close contacts we make with others, isolating cases after they are diagnosed, closing schools, quarantining households, quarantining individuals who are known to have been exposed to a case, and using antiviral drugs treat and protect people at ri ....The aim of this study is to help us prepare for a pandemic of influenza by comparing how effective the various available control strategies are at reducing transmission of the disease. The available control interventions include: reducing the number of close contacts we make with others, isolating cases after they are diagnosed, closing schools, quarantining households, quarantining individuals who are known to have been exposed to a case, and using antiviral drugs treat and protect people at risk of being infected. We will compare these control measures by taking due account of the ability and resources available for these interventions, and with regard to the need to maintain essential services. The comparisons will be made using mathematical models that describe the transmission of the infection. All available data and advice from experts will be used to ensure that realistic models are used for the comparisons. We will also use the models to determine the best use of the limited antiviral drugs available, until a vaccine becomes available. We will consider how the control strategy should be changed if a strain develops that is resistant to the antiviral drugs. In addition, we will determine what data need to be collected during the early stages of a pandemic to help us to determine the best use of the antiviral drugs, the best use of a new vaccine and to check on the development of resistance to the antiviral drugs.Read moreRead less
Marine Natural Products as Sources of Agrochemicals - The Variolins. The aim of this project is the identification of new classes of agrochemicals with better pest resistance and environmental profiles. The proposed partnership with a major international chemical manufacturing organization will allow access to state-of-the-art techniques for the screening and development of novel compounds as agents for the control of pests that affect many major agricultural crops relevant to Australia's econo ....Marine Natural Products as Sources of Agrochemicals - The Variolins. The aim of this project is the identification of new classes of agrochemicals with better pest resistance and environmental profiles. The proposed partnership with a major international chemical manufacturing organization will allow access to state-of-the-art techniques for the screening and development of novel compounds as agents for the control of pests that affect many major agricultural crops relevant to Australia's economy. Australian graduate students will experience the operations of one of the world's biggest chemical manufacturers. The derivation of agrochemicals from marine sources will promote further recognition of the value of marine ecosystems around Australia.Read moreRead less
Preventing and addressing environmental harm through restorative justice. This project aims to develop a knowledge base on how Restorative Justice (RJ) principles and practices can prevent and address environmental harm. Research has demonstrated that RJ is a powerful response to a wide variety of governance challenges and could provide a useful alternative paradigm for environmental regulation. This project aims to apply the processes and values of RJ to environmental regulation with a focus on ....Preventing and addressing environmental harm through restorative justice. This project aims to develop a knowledge base on how Restorative Justice (RJ) principles and practices can prevent and address environmental harm. Research has demonstrated that RJ is a powerful response to a wide variety of governance challenges and could provide a useful alternative paradigm for environmental regulation. This project aims to apply the processes and values of RJ to environmental regulation with a focus on harm prevention, advancing theory into a new domain of application. This should lead to immediate and long-term benefits, including better prevention of environmental harm, better relationships with communities, and stronger commitments by those who have caused harm to rehabilitate, repair and reform.Read moreRead less
Setting Priorities for Services Trade Reform. Services could be a deal maker in the Doha Round of trade negotiations, and Australia has much to gain if developing countries can be persuaded to make commercially meaningful commitments to liberalise services trade. Australia will also gain if the economies of the region are strengthened through regulatory reform. And Australia can gain from further regulatory reform at home. To these ends, the project will provide new understanding of regulatory b ....Setting Priorities for Services Trade Reform. Services could be a deal maker in the Doha Round of trade negotiations, and Australia has much to gain if developing countries can be persuaded to make commercially meaningful commitments to liberalise services trade. Australia will also gain if the economies of the region are strengthened through regulatory reform. And Australia can gain from further regulatory reform at home. To these ends, the project will provide new understanding of regulatory best practice that will reveal the priorities for services trade reform. Read moreRead less
Development of environmentally-friendly bioinsecticides for control of Australian crop pests. Insect pests cause over $3 billion of damage each year to Australian crops. Current insecticides are becoming less effective, and they often have adverse environmental impacts. This project aims to develop a new generation of environmentally-friendly insecticides that can be used to control insect pests on farms and around the home and garden.
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.
Non-urban water governance: rethinking compliance and enforcement. This project aims to critically evaluate the practices and strategies of non-urban water compliance and enforcement in Australia and internationally, to identify and develop innovations for water governance. New law and policy knowledge is expected from its fusion of empirical data and regulatory theory. The project expects to advance applied regulatory theory by identifying improvements in compliance and enforcement to help solv ....Non-urban water governance: rethinking compliance and enforcement. This project aims to critically evaluate the practices and strategies of non-urban water compliance and enforcement in Australia and internationally, to identify and develop innovations for water governance. New law and policy knowledge is expected from its fusion of empirical data and regulatory theory. The project expects to advance applied regulatory theory by identifying improvements in compliance and enforcement to help solve environmental issues. It will also lead to policy reforms for delivering more effective, efficient and politically-acceptable compliance outcomes for non-urban water management that will benefit water regulators and the sustainability and productivity of Australia's agricultural industry.Read moreRead less