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
Symmetries in CR-geometry. This project aims at investigating symmetries of geometric objects called CR-manifolds. It is expected to open new avenues for understanding such symmetries at the infinitesimal level and lead to ground-breaking results in CR-geometry. Expected outcomes include new methodology, solving long-standing problems, and establishing international research collaborations. The benefits are in enhancing the strength of the research in analysis and geometry performed in Australia ....Symmetries in CR-geometry. This project aims at investigating symmetries of geometric objects called CR-manifolds. It is expected to open new avenues for understanding such symmetries at the infinitesimal level and lead to ground-breaking results in CR-geometry. Expected outcomes include new methodology, solving long-standing problems, and establishing international research collaborations. The benefits are in enhancing the strength of the research in analysis and geometry performed in Australia, in fostering the international competitiveness of Australian research and in high-quality research training.Read moreRead less
Nilpotent associative algebras and spherical hypersurfaces. This project concerns pure basic research in mathematics and is based on an important recently discovered relationship between certain geometric and algebraic objects. In the project, this relationship will be applied in a novel way to solve several significant long-standing problems in the research area of complex geometry.
The Reconstruction and Recognition Problems for Hypersurface Singularities. This project concerns pure basic research in mathematics. It is centred around a surprising relationship between geometric objects called quasi-homogeneous isolated hypersurface singularities, and algebraic structures described as Artinian Gorenstein algebras. This relationship has not been fully understood despite numerous attempts by internationally based experts to shed light on it. Armed with a novel approach to Arti ....The Reconstruction and Recognition Problems for Hypersurface Singularities. This project concerns pure basic research in mathematics. It is centred around a surprising relationship between geometric objects called quasi-homogeneous isolated hypersurface singularities, and algebraic structures described as Artinian Gorenstein algebras. This relationship has not been fully understood despite numerous attempts by internationally based experts to shed light on it. Armed with a novel approach to Artinian Gorenstein algebras, this project proposes to clarify the nature of this relationship and utilise it for solving related geometric and algebraic problems. In particular, it aims at obtaining a groundbreaking result in the area of classical invariant theory.Read moreRead less
Proper Group Actions in Complex Geometry. The results of the project will enhance Australia's performance in several key mathematical areas as well as mathematical applications to physics critical for expanding Australia's knowledge base and research capability. The project has strong international aspects, it will foster the international competitiveness of Australian research and establish long-term collaborations between Australian researchers and high profile world experts in the area of the ....Proper Group Actions in Complex Geometry. The results of the project will enhance Australia's performance in several key mathematical areas as well as mathematical applications to physics critical for expanding Australia's knowledge base and research capability. The project has strong international aspects, it will foster the international competitiveness of Australian research and establish long-term collaborations between Australian researchers and high profile world experts in the area of the proposal. It will create an opportunity for a Ph.D. graduate to be involved in top-class research as a Research Associate, and will attract Ph.D. and honours students thus enabling research training in a high-quality mathematical environment.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
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.
Symmetry and geometric structures. This is a fundamental research project in mathematics, especially concerned with the interaction between symmetry, differential equations, and geometry. Based on many classical and recently discovered instances, the aim of the project is to use symmetries to build and understand curved geometric structures from their flat counterparts.
Development Of Therapeutically Useful Human Artificial Chromosomes For Gene Delivery And Optimal Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$496,986.00
Summary
Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in ....Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in terms of infection, immune response, and germline modification. We have developed the first stage of a new technology for gene delivery that does not require the use of viruses. This technology is based on the generation of human artificial chromosomes, which are smaller versions of the naturally occurring chromosomes that carry all the genes inside our cells. Safety in these artificial chromosomes comes from the use of entirely human materials for their engineering. These artificial chromosomes also have other advantages over the viral approaches, including allowing large genes to be carried, and providing a permanent cure in a single treatment. We have already successfully constructed, published, and patented a number of first-generation human artificial chromosomes. The current project aims to complete the next proof-of-concept milestone towards the further development of this technology. Specifically, we propose to demonstrate the ability of the artificial chromosomes to carry genes and provide sustainable expression of these genes in cells and in animal models. Success in this study will allow the technology to proceed rapidly into commercialisation and clinical trial as a new improved tool for gene delivery and gene therapy.Read moreRead less