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: LE0989564
Funder
Australian Research Council
Funding Amount
$150,000.00
Summary
State-of-the-art facility for human and animal virus research in the Canberra and surrounding regions. New viral diseases continue to emerge and old viruses re-emerge to pose a threat to human and animal health. To combat these, we propose a dedicated viral disease research facility. The centre will include experienced researchers, biotechnology companies and government agencies working on discovery, prevention and treatment of viral diseases. Forging strong scientific links between these organi ....State-of-the-art facility for human and animal virus research in the Canberra and surrounding regions. New viral diseases continue to emerge and old viruses re-emerge to pose a threat to human and animal health. To combat these, we propose a dedicated viral disease research facility. The centre will include experienced researchers, biotechnology companies and government agencies working on discovery, prevention and treatment of viral diseases. Forging strong scientific links between these organisations will considerably enhance the productivity of these researchers, increase their collaborative and scientific outputs and allow for training of students in the latest technologies. The facility will provide researchers with cutting-edge instrumentation for nationally and internationally important projects that would benefit human health.Read moreRead less
Special Research Initiatives - Grant ID: SR0354888
Funder
Australian Research Council
Funding Amount
$30,000.00
Summary
Australian Research Council Research Network for Parasitology. Parasites are a major cause of death and suffering in humans and animals throughout the world. The ARC Research Network for Parasitology aims to bring together Australia's finest researchers and establish a world class environment and web of facilities that attracts and retains the most talented young investigators and places Australia in a strong position to deal with current and future parasitological threats. The Network will focu ....Australian Research Council Research Network for Parasitology. Parasites are a major cause of death and suffering in humans and animals throughout the world. The ARC Research Network for Parasitology aims to bring together Australia's finest researchers and establish a world class environment and web of facilities that attracts and retains the most talented young investigators and places Australia in a strong position to deal with current and future parasitological threats. The Network will focus and enhance Australia's fundamental, strategic and applied parasitology research capabilities to :
(1) develop new approaches to vaccination;
(2) identify novel drug targets; and
(3) ensure the sustainability of wildlife and ecosystem health.
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ARC/NHMRC Research Network for Parasitology. The ARC Network for Parasitology will focus and coordinate Australia's world class fundamental, strategic and applied parasitology research. This targeted approach will raise Australia's standing in the field, assist in the community's understanding of parasitology and biosecurity and maintain and improve Australia's capacity for keeping its stock, crops, wildlife and people disease-free. On an international scale, the Network will work with other cou ....ARC/NHMRC Research Network for Parasitology. The ARC Network for Parasitology will focus and coordinate Australia's world class fundamental, strategic and applied parasitology research. This targeted approach will raise Australia's standing in the field, assist in the community's understanding of parasitology and biosecurity and maintain and improve Australia's capacity for keeping its stock, crops, wildlife and people disease-free. On an international scale, the Network will work with other countries to develop new technologies for the detection and eradication of parasites. This emphasis will not only protect Australia's borders but will assist our near neighbours and lead to the development of technologies with an economic benefit to Australia.
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ARC Centre of Excellence - Structural and Functional Microbial Genomics. The research falls under the National Research Priority Frontier Technologies for Building and Transforming Australian Industries, with the priority goal of frontier technologies. The research has commercial applications, such as the development of novel antimicrobials and vaccines, with potentially enormous impact in the biotechnology area of biomedical health and the primary industries. In addition, the project will use ....ARC Centre of Excellence - Structural and Functional Microbial Genomics. The research falls under the National Research Priority Frontier Technologies for Building and Transforming Australian Industries, with the priority goal of frontier technologies. The research has commercial applications, such as the development of novel antimicrobials and vaccines, with potentially enormous impact in the biotechnology area of biomedical health and the primary industries. In addition, the project will use state-of-the-art technology, including use of synchrotron radiation at the Monash-based Australian Synchrotron facility from 2007.Read moreRead less
ARC Centre for Structural & Functional Microbial Genomics. Australian Primary Industry will benefit from a team of experts in microbial genetics, bioinformatics and protein structure and function undertaking integrated studies on microbial genomics and phenomics that are focused on fundamental biological processes and host/pathogen interactions. Whole genome expression and protein profiling will be used to characterise genes whose expression is altered in the infected host and to analyse genes i ....ARC Centre for Structural & Functional Microbial Genomics. Australian Primary Industry will benefit from a team of experts in microbial genetics, bioinformatics and protein structure and function undertaking integrated studies on microbial genomics and phenomics that are focused on fundamental biological processes and host/pathogen interactions. Whole genome expression and protein profiling will be used to characterise genes whose expression is altered in the infected host and to analyse genes involved in the control of key cellular processes. The Centre will also determine the shapes of key molecules and their interactions. Practical outcomes will include new veterinary vaccines and the identification of novel antimicrobial targets.Read moreRead less
The molecular basis for oocyst and cyst wall formation in apicomplexan parasites. Apicomplexan parasites such as Eimeria, Neospora, Toxoplasma and Plasmodium are single celled organisms - protozoa - that cause some of the most serious infectious diseases of livestock and humans ever known. Transmission of these parasites is dependent on their ability to encase themselves in protective structures known as oocyst or cyst walls. These walls are resistant to harsh environmental conditions, chemicals ....The molecular basis for oocyst and cyst wall formation in apicomplexan parasites. Apicomplexan parasites such as Eimeria, Neospora, Toxoplasma and Plasmodium are single celled organisms - protozoa - that cause some of the most serious infectious diseases of livestock and humans ever known. Transmission of these parasites is dependent on their ability to encase themselves in protective structures known as oocyst or cyst walls. These walls are resistant to harsh environmental conditions, chemicals and attack by the immune system. We will discover and characterise the molecular basis for cyst wall formation. This fundamental knowledge will be the building block for new, highly specific drugs and vaccines to control these extremely important pathogens.Read moreRead less
The role of neutral amino acid transport in normal physiology. Future benefits of these studies include the Promotion and Maintenance of Good Health achieved by providing: (1) a better understanding of brain and balance disorders; (2) insights into the damaging effects of the sun and; (3) existing neonatal screening programmes for Hartnup disorder with greater scientific foundation regarding the implications of inheriting this condition, including dietary advce. We will be able to provide Austr ....The role of neutral amino acid transport in normal physiology. Future benefits of these studies include the Promotion and Maintenance of Good Health achieved by providing: (1) a better understanding of brain and balance disorders; (2) insights into the damaging effects of the sun and; (3) existing neonatal screening programmes for Hartnup disorder with greater scientific foundation regarding the implications of inheriting this condition, including dietary advce. We will be able to provide Australians who inherit Hartnup disorder with a better understanding of this disease by enabling individuals and families to make choices that lead to healthy, productive and fulfilling lives.Read moreRead less