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
Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. Inte ....Epigenetic silencing in vertebrates: evolution and function from the bottom-up. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional genomics in Australia, with the research priority of Frontier Technologies for Building and Transforming Australian Industries and priority goals in Breakthrough Science and Frontier Technologies. This project focuses on important biological questions surrounding gene regulation and sex chromosome evolution. International attention has already resulted in genome characterization of Australian icons (wallaby, Tasmanian devil and platypus), more research on these, and other Australian animals, will further highlight the importance of Australian fauna and impact positively on our scientific profile.Read moreRead less
Origin and Evolution of Mammalian Dosage Compensation. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional comparative genomics in Australia, with the research priority of 'Frontier Technologies for Building and Transforming Australian Industries' and priority goals in 'Breakthrough Science and Frontier Technologies'. This project addresses fundamental questions about the evolution of mammalian X-chromosome inactivation, of importance as a mo ....Origin and Evolution of Mammalian Dosage Compensation. The primary benefits are contribution to Australia's knowledge base and raising the profile of functional comparative genomics in Australia, with the research priority of 'Frontier Technologies for Building and Transforming Australian Industries' and priority goals in 'Breakthrough Science and Frontier Technologies'. This project addresses fundamental questions about the evolution of mammalian X-chromosome inactivation, of importance as a model for epigenetic change, and sex chromosomes, which has engaged some of the greatest genetic minds over nearly a century. Therefore my results will attract wide international interest and impact positively on Australia's scientific profile, and further highlight the importance of Australian mammals.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.
The Origin and Evolution of the Animal Phyla inferred from Analysis of Multiple-Gene Data. Australia has recently begun an extensive research programme in the genomics of our flora and fauna. The enormous amounts of data that emerge from such research are highly complex, but they hold the key to understanding how biological organisms change over time. Our research will untangle that data to answer fundamental, unanswered questions in modern science: How did the animal groups originate? How are ....The Origin and Evolution of the Animal Phyla inferred from Analysis of Multiple-Gene Data. Australia has recently begun an extensive research programme in the genomics of our flora and fauna. The enormous amounts of data that emerge from such research are highly complex, but they hold the key to understanding how biological organisms change over time. Our research will untangle that data to answer fundamental, unanswered questions in modern science: How did the animal groups originate? How are they related to each other? How is biodiversity changing? The answers to these questions and the new analytical tools we will develop will put Australia firmly on the international "map" of Bioinformatics.Read moreRead less
Understanding somatic mutation in plants: new methods, new software, new data. Somatic mutations accumulate as plants grow, affecting everything from short-term ecological interactions to long-term evolutionary dynamics. These mutations have important consequences for plant industry and conservation, but because they are so hard to measure almost nothing is known about them. This project aims to develop new methods and software to detect, analyse, and compare the genome-wide history of somatic m ....Understanding somatic mutation in plants: new methods, new software, new data. Somatic mutations accumulate as plants grow, affecting everything from short-term ecological interactions to long-term evolutionary dynamics. These mutations have important consequences for plant industry and conservation, but because they are so hard to measure almost nothing is known about them. This project aims to develop new methods and software to detect, analyse, and compare the genome-wide history of somatic mutation in individual plants, providing an unprecedented level of detail into an important but understudied source of biological variation. By applying these methods to an iconic experimental population, This project aims to provide the first insights into the genome-wide causes and consequences of somatic mutation in plants.Read moreRead less
Global climate change and coastal landscape evolution in southern Australia. This project aims to reconstruct environmental changes that occurred in southern Australia during a geologically recent time interval termed the Early-Middle Pleistocene Transition (1.2 million to 700 thousand years ago) and an interglacial period some 400,000 years ago. Using innovative geochronological, geochemical and modelling techniques, the environmental changes that shaped modern Australian coastal landscapes, in ....Global climate change and coastal landscape evolution in southern Australia. This project aims to reconstruct environmental changes that occurred in southern Australia during a geologically recent time interval termed the Early-Middle Pleistocene Transition (1.2 million to 700 thousand years ago) and an interglacial period some 400,000 years ago. Using innovative geochronological, geochemical and modelling techniques, the environmental changes that shaped modern Australian coastal landscapes, including the intensification of aridity and their timing will be examined. The project will yield new knowledge about the sensitivity of landscapes to current and ongoing environmental changes and derive explanatory models of the rates and characteristics of landscape response to assist future coastal environmental management.Read moreRead less
The Epigenetics of Sex in the Dragon. Genetic codes do not directly translate to phenotypes -- environment acts through epigenetics to modify development. We use advanced molecular techniques to examine how epigenetics responds to temperature to reverse sex in our novel animal model, the dragon lizard. How does the cell sense temperature? Once the extrinsic signal is captured, how does it influence chromatin modification to release or suppress key genes in the sex differentiation pathway? Which ....The Epigenetics of Sex in the Dragon. Genetic codes do not directly translate to phenotypes -- environment acts through epigenetics to modify development. We use advanced molecular techniques to examine how epigenetics responds to temperature to reverse sex in our novel animal model, the dragon lizard. How does the cell sense temperature? Once the extrinsic signal is captured, how does it influence chromatin modification to release or suppress key genes in the sex differentiation pathway? Which sex genes are targets? Epigenetic enzymes are astonishingly conserved, providing exciting opportunities to draw from human systems to unravel novel signatures of temperature-induced sex switching in reptiles. This project will advance knowledge of developmental programming generally.Read moreRead less
Analysing and modelling molecular rate variation among nuclear and mitochondrial genomes. My research will have important practical benefits for bioinformaticians and evolutionary biologists, because existing analytical methods will be rigorously tested and new tools will be developed. Australia has a comparatively high concentration of researchers in this field, so my research will foster domestic collaboration and import international expertise. The research will provide important insights int ....Analysing and modelling molecular rate variation among nuclear and mitochondrial genomes. My research will have important practical benefits for bioinformaticians and evolutionary biologists, because existing analytical methods will be rigorously tested and new tools will be developed. Australia has a comparatively high concentration of researchers in this field, so my research will foster domestic collaboration and import international expertise. The research will provide important insights into the rates and patterns of genetic changes associated with domestication, and into variation in evolutionary rates among the primate ancestors of humans. In addition to developing new software, which will be made publicly available, I will develop new evolutionary models to supplement existing software packages. Read moreRead less