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.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE210100001
Funder
Australian Research Council
Funding Amount
$875,000.00
Summary
A 3-photon imaging system for deep live imaging. This project aims to establish Australia’s first 3-photon microscope system with adaptive optics for deep intravital imaging. This advanced imaging system will enable researchers to investigate the biology of cells and tissue structures in a wide range of organs and engineered tissues, to a degree not possible with existing technology. This project will capitalise on advanced laser, microscope and adaptive optics technologies with the expected out ....A 3-photon imaging system for deep live imaging. This project aims to establish Australia’s first 3-photon microscope system with adaptive optics for deep intravital imaging. This advanced imaging system will enable researchers to investigate the biology of cells and tissue structures in a wide range of organs and engineered tissues, to a degree not possible with existing technology. This project will capitalise on advanced laser, microscope and adaptive optics technologies with the expected outcomes to include the generation of new knowledge of major biological systems, including the immune system and the nervous system. This will provide significant benefits to fundamental interdisciplinary research into immunology, infectious disease, neuroscience, mechanobiology and engineering.Read moreRead less
Immunological mechanisms underlying the protective immune responses induced by botulinum oil adjuvanted vaccine. Botulism is recognised as an important bacterial pathogen in commercial beef cattle in Australia and around the world. Development of affective, well-researched vaccine against Clostridium botulinum is a high priority for the cattle industry. A novel oil adjuvanted vaccine (Singvac from Fort Dodge Pty Ltd) has advantage over conventional vaccines as it provides full protection follo ....Immunological mechanisms underlying the protective immune responses induced by botulinum oil adjuvanted vaccine. Botulism is recognised as an important bacterial pathogen in commercial beef cattle in Australia and around the world. Development of affective, well-researched vaccine against Clostridium botulinum is a high priority for the cattle industry. A novel oil adjuvanted vaccine (Singvac from Fort Dodge Pty Ltd) has advantage over conventional vaccines as it provides full protection following a single administration. The aims of this study are to investigate the immunological mechanisms underlying the protective response by this novel vaccine using bovine and murine models. This study will discover new control measures for botulism in Australia.Read moreRead less
Mitigating ecosystem impacts by improving the way we breed and manage devils. The Tasmanian ecosystem faces irreversible change due to the decline of the apex predator. An insurance population of Tasmanian devils has been established to prevent extinction of the species. Using the latest sequencing technologies the project aims to determine whether the Tasmanian ecosystem can be restored with Tasmanian devils that are more resilient to a changing environment by improving the way that devils are ....Mitigating ecosystem impacts by improving the way we breed and manage devils. The Tasmanian ecosystem faces irreversible change due to the decline of the apex predator. An insurance population of Tasmanian devils has been established to prevent extinction of the species. Using the latest sequencing technologies the project aims to determine whether the Tasmanian ecosystem can be restored with Tasmanian devils that are more resilient to a changing environment by improving the way that devils are bred and managed in captivity.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561251
Funder
Australian Research Council
Funding Amount
$150,887.00
Summary
Facility for Analyses of Evolutionary Immunology. Our understanding of how selection in natural populations shape (favour and disfavour) immunity, and how this process contribute to organismal (including human) fitness, is rudimentary. In order to study such processes our collective experience strongly suggests and increasing need for geographic amalgamation of necessary and complementary molecular and biomedical techniques. We therefore request funding to establish a collaborative research labo ....Facility for Analyses of Evolutionary Immunology. Our understanding of how selection in natural populations shape (favour and disfavour) immunity, and how this process contribute to organismal (including human) fitness, is rudimentary. In order to study such processes our collective experience strongly suggests and increasing need for geographic amalgamation of necessary and complementary molecular and biomedical techniques. We therefore request funding to establish a collaborative research laboratory in a novel research field - Evolutionary Immuno-Ecology- in which all vital aspects, from a mechanistic to an evolutionary level, can be studied at one research centre.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE130100210
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
In-vivo, high-resolution, whole animal imaging . The purchase of state-of-the-art live-animal imaging equipment for use by researchers at The Australian National University and The University of New South Wales. This equipment will aid the study of many aspects of normal biology and disease including cancer, inflammation, autoimmune diseases and blood vessel disorders.