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.
Mechanisms And Therapies In Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,360,700.00
Summary
Cardiovascular disease (CVD) claims 1 person every 10 min in Australia and causes 1 in 3 deaths worldwide. The molecular and cellular processes underlying atherosclerosis, vascular injury and thrombosis are highly complex and not well understood. A multifaceted approach is needed to effectively address these key challenges. This Program brings together world experts in these areas to interrogate gaps in our basic understanding of CVD, and to develop novel therapies for CVD patients by exploiting ....Cardiovascular disease (CVD) claims 1 person every 10 min in Australia and causes 1 in 3 deaths worldwide. The molecular and cellular processes underlying atherosclerosis, vascular injury and thrombosis are highly complex and not well understood. A multifaceted approach is needed to effectively address these key challenges. This Program brings together world experts in these areas to interrogate gaps in our basic understanding of CVD, and to develop novel therapies for CVD patients by exploiting new knowledge through integrated research.Read moreRead less
Estimating And Alleviating The Impacts Of Age-Related Sensory Decline
Funder
National Health and Medical Research Council
Funding Amount
$323,767.00
Summary
Sensory loss and dementia disproportionately affect older adults, often co-occur, and are the two leading contributors to disability burden among older Australians. This research will investigate the consequences that hearing and vision loss have for older adult health and wellbeing, informing strategies to reduce the disability burden of age-related sensory loss. These impacts include cognitive decline and dementia, mental health, quality of life, disability and independent living.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Temperature sensitivity of soil respiration and its components. This project aims to demonstrate how temperate evergreen forests could buffer against climate change. Soil respiration returns around half the carbon taken up by forests to the atmosphere. This project will characterise and quantify how microbes and roots in soils depend on temperature and substrate supply, and so predict how rising temperatures and drought will affect forests as natural carbon sequestration sinks. This project will ....Temperature sensitivity of soil respiration and its components. This project aims to demonstrate how temperate evergreen forests could buffer against climate change. Soil respiration returns around half the carbon taken up by forests to the atmosphere. This project will characterise and quantify how microbes and roots in soils depend on temperature and substrate supply, and so predict how rising temperatures and drought will affect forests as natural carbon sequestration sinks. This project will resolve the roles of environmental drivers of soil respiration across forests; integrate mechanistic understanding of differing plant and microbial responses to temperature within a common modelling framework; and evaluate the implications of this knowledge in predictions of climatic impacts on terrestrial carbon cycling.Read moreRead less
To grow or to store: Do plants hedge their bets? This project aims to resolve a long-standing question about the function of perennial plants: how much of the carbon taken up by photosynthesis is used immediately for growth, and how much is kept in reserve as insurance against future stress? This question is important to our understanding of how plants respond to stresses such as severe drought, and yet lack of data and theoretical modelling currently hampers our ability to answer it. By applyin ....To grow or to store: Do plants hedge their bets? This project aims to resolve a long-standing question about the function of perennial plants: how much of the carbon taken up by photosynthesis is used immediately for growth, and how much is kept in reserve as insurance against future stress? This question is important to our understanding of how plants respond to stresses such as severe drought, and yet lack of data and theoretical modelling currently hampers our ability to answer it. By applying novel data analysis and modelling tools to recent experimental results, the project plans to test hypotheses for how plants allocate carbon between growth and storage in response to stress. Insights from the project may underpin better management of Australia’s vulnerable ecosystems.Read moreRead less
Optimising the spring in your step to enhance footwear design. This project aims to examine how the nervous system adjusts the mechanical function of our feet across a spectrum of speeds, from slow running through to maximal effort sprinting. The proposed research will explore how the nervous system controls the function of the foot to meet the ever-varying demands of locomotion in the real-world. Expected outcomes of this project are to determine if running shoes help or hinder the natural spri ....Optimising the spring in your step to enhance footwear design. This project aims to examine how the nervous system adjusts the mechanical function of our feet across a spectrum of speeds, from slow running through to maximal effort sprinting. The proposed research will explore how the nervous system controls the function of the foot to meet the ever-varying demands of locomotion in the real-world. Expected outcomes of this project are to determine if running shoes help or hinder the natural spring-like function of the foot. It will explain a conceptually novel design allowing shoes to support our feet, whilst harnessing the energetic benefits of the foot's spring-like function. This research has the potential to revolutionise athletic footwear design and has direct implications for enhanced performance in running athletes.Read moreRead less
Linking phytoplankton to fisheries using zooplankton size spectra. This project aims to develop innovative numerical methods to understand the dynamics, carbon export, and trophic structure of zooplankton. The trophic links between phytoplankton, zooplankton and fisheries are unknown. The size- frequency distribution of zooplankton (size spectrum) is an innovative method for estimating their growth, predation and production as food for fish. Analysis of a global synthesis of zooplankton size dis ....Linking phytoplankton to fisheries using zooplankton size spectra. This project aims to develop innovative numerical methods to understand the dynamics, carbon export, and trophic structure of zooplankton. The trophic links between phytoplankton, zooplankton and fisheries are unknown. The size- frequency distribution of zooplankton (size spectrum) is an innovative method for estimating their growth, predation and production as food for fish. Analysis of a global synthesis of zooplankton size distributions from tropical to polar environments are expected to reveal these vital rates of pelagic ecosystems. The zooplankton rates will reveal, for the first time, the link between phytoplankton and fisheries, and will significantly improve ecosystem models and global assessments of environmental change.Read moreRead less