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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
Mechanisms Of Induction And Progression Of Childhood Asthma: Investigations In A Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$517,586.00
Summary
This project investigates how certain respiratory viral infections in very young children might predispose to developing asthma, and how inflammation in the airways in asthma might then worsen. The experimental work, which will use unique mouse models developed in the laboratories of the chief investigators, will focus on changes in genes that control the pattern of immune response to allergens and that regulate the progression of inflammation.
Discovery Of A Novel Immune Evasion Strategy Employed By Mosquito Borne Viruses To Suppress Antiviral Immune Responses
Funder
National Health and Medical Research Council
Funding Amount
$418,642.00
Summary
The transition from mosquitoes, ticks, or other invertebrate vectors to the human hosts represents a crucial step in the successful establishment of arthropod borne viruses (arboviruses). The incidence of arbovirus infections such as dengue virus, West Nile virus, Ross River virus is increasing at an alarming rate in various parts of the world. In addition, the emergence of new viruses resulting in significant mortality in the population is of utmost concern. Vaccines for many of these viruses r ....The transition from mosquitoes, ticks, or other invertebrate vectors to the human hosts represents a crucial step in the successful establishment of arthropod borne viruses (arboviruses). The incidence of arbovirus infections such as dengue virus, West Nile virus, Ross River virus is increasing at an alarming rate in various parts of the world. In addition, the emergence of new viruses resulting in significant mortality in the population is of utmost concern. Vaccines for many of these viruses remain elusive. One factor that contributes to this is the ability of viruses to develop ingenious strategies to avoid or suppress the host defence systems, which enable its successful establishment in the host. Understanding how viruses evade-suppress host defence machinery will certainly enhance and improve our approaches to fight them. For the first time internationally we have discovered a new and novel pathway employed by arboviruses to suppress antiviral immune responses in the host. We have discovered that naturally occurring carbohydrates on viruses derived from mosquito cells, would influence these virus s ability to evade-suppress host antiviral proteins such as interferons. This may be a general effect of arboviruses or may even extend to other viruses , which include a number of deadly pathogens (HIV, Influenza). This research has the potential to significantly expand our understanding of how these viruses establish infection and cause disease. Also this discovery has broader implications for understanding inflammatory processes and their regulation.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
Molecular and genetic analysis of epigenetic components in a model plant. Australia is a major exporter of agricultural food crops thus producers must maintain their competitive advantage in order to compete on the world stage. Food crops unfortunately have large, complex genomes that are not sequenced and a generation time of months that makes research outcomes slow to achieve. This project proposes to utilise a model plant that has a small completely sequenced genome and a short generation tim ....Molecular and genetic analysis of epigenetic components in a model plant. Australia is a major exporter of agricultural food crops thus producers must maintain their competitive advantage in order to compete on the world stage. Food crops unfortunately have large, complex genomes that are not sequenced and a generation time of months that makes research outcomes slow to achieve. This project proposes to utilise a model plant that has a small completely sequenced genome and a short generation time making it ideal to study the fundamental biological process of RNA silencing. Discoveries and outcomes from this project may have the potential to benefit Australian crops, ecosystems and human health.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.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE120100098
Funder
Australian Research Council
Funding Amount
$230,000.00
Summary
A comprehensive gas/vapour sorption facility for the fast advancement of decarbonised energy technologies. Solutions to clean energy production, storage and use are critical to Australia’s prosperity, yet there is a significant lack of targeted research facilities for the development of the highly needed materials and technologies for powering a sustainable Australia. This facility will bring research efforts closer to practical solutions.
Rebuilding Southern Rock Lobster Stocks On The East Coast Of Tasmania: Informing Options For Management
Funder
Fisheries Research and Development Corporation
Funding Amount
$103,800.00
Summary
Rock lobster stocks off the east coast of Tasmania are in a depleted state and as a consequence a stock rebuilding strategy has been implemented. This has involved adopting a 200 tonnes east coast catch limit, comprising a catch cap for the commercial sector and a notional catch share for the recreational sector. While the commercial catch limit can be monitored and controlled directly, management of the recreational catch share is more problematic.
The recreational rock lobster fishery ....Rock lobster stocks off the east coast of Tasmania are in a depleted state and as a consequence a stock rebuilding strategy has been implemented. This has involved adopting a 200 tonnes east coast catch limit, comprising a catch cap for the commercial sector and a notional catch share for the recreational sector. While the commercial catch limit can be monitored and controlled directly, management of the recreational catch share is more problematic.
The recreational rock lobster fishery has been monitored for two decades, during which time there have been significant management changes and variability in stock abundance. The greatest changes have occurred in the east coast, which has traditionally attracted 60-70% of the state-wide recreational catch and effort. In an effort to restrict catches from that region there have been drastic reductions in bag and possession limits and a progressive reduction in season. Furthermore, major biotoxin events have resulted in closures of key areas during peak fishing periods.
High and varying levels of participation has made management of the recreational component of the fishery difficult. This situation is likely to be further exacerbated as stocks rebuild; higher catch rates are expected to attract increased effort and overall catches for the sector. For the commercial sector, the catch cap effectively represents a competitive or “Olympic” catch quota which, as catch rates improve, is likely to influence fleet dynamics and timing of catches as fishers ‘race’ to take the limited catch.
Understanding relationships between fisher behaviour, their expectations/aspirations, responses to changes in stock status and to management intervention is critical when implementing effective management strategies. This project aims to inform on the practical challenges to achieving the stock rebuilding objective and provide options to assist managers and both fishing sectors in achieving the ecological, social and economic goals for the fishery.
Objectives: 1. Determine the relationships between recreational fisher behaviour (effort and participation) and Rock Lobster catch rates and abundance 2. Assess fisher attitudes and compliance behaviour to management scenarios designed to achieve the east coast stock rebuilding objective 3. Model the effectiveness of alternative management scenarios in constraining recreational catches as stock rebuild 4. Model the impact on fleet dynamics, including economic implications, of the expected shift to an "Olympic" quota. 5. Evaluate the costs and benefits of short- and long-term management options for the east coast Rock Lobster fishery Read moreRead less
It is feasible to sequence patient genomes but we need to know more about how genetic variants cause complex disease. We have sequenced genomes from patients with immune deficiency and will test the idea that genetic variation causes consistent changes in particular white blood cells, thus providing a bridge between genomic information and clinical diagnosis. Outcomes will include more accurate diagnosis, better understanding of immunity, and a strategy for using whole genome information.