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
Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly whe ....Elucidating the Mode of Action of Nicotinic Receptor Ligands. Changes in brain function can cause human diseases such as epilepsy, schizophrenia and Alzheimer's disease. To develop new medicines to treat these conditions we need to study how drugs act in the brain. This project will use new methods of chemistry to make drugs, which will then be tested for biological activity at important brain receptors. This will tell us which compounds are most effective as potential drugs and also exactly where they act in the brain. Read moreRead less
Force from lipids: the role of the lipid bilayer in mechanosensory transduction. The proposed research will significantly contribute to a better understanding of the wide range of physiological processes underlying mechanosensory transduction in living cells. The direct benefit for Australian science consists of: (i) strengthening international links with leading overseas laboratories, and (ii) accessing the state-of-the-art expertise not available in Australia. The acquired knowledge will aid i ....Force from lipids: the role of the lipid bilayer in mechanosensory transduction. The proposed research will significantly contribute to a better understanding of the wide range of physiological processes underlying mechanosensory transduction in living cells. The direct benefit for Australian science consists of: (i) strengthening international links with leading overseas laboratories, and (ii) accessing the state-of-the-art expertise not available in Australia. The acquired knowledge will aid in developing and designing artificial tactile sensors inspired by their biological models studied in this project. Long-term, the project is expected to make an original contribution towards developing new technologies and novel medical applications, both of which promise to be of great national benefit.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0882289
Funder
Australian Research Council
Funding Amount
$520,000.00
Summary
New generation mass spectrometers for characterisation of molecular shape and size. The ion mobility mass spectrometer (IMMS at UOW) will be the first of its kind in Australia, and together with the ion trap mass spectrometer (ITMS at ANU) will continue the tradition of this partnership in providing researchers with cutting-edge instrumentation for nationally and internationally important projects including: (i) fundamental understanding of the ways in which biomolecules recognize one another, ( ....New generation mass spectrometers for characterisation of molecular shape and size. The ion mobility mass spectrometer (IMMS at UOW) will be the first of its kind in Australia, and together with the ion trap mass spectrometer (ITMS at ANU) will continue the tradition of this partnership in providing researchers with cutting-edge instrumentation for nationally and internationally important projects including: (i) fundamental understanding of the ways in which biomolecules recognize one another, (ii) investigating the structure(s) of lipids (fats) in cardiovascular disease and cataract, (iii) developing anticancer drugs, and (iv) development of new materials.Read moreRead less
ARC Centre of Excellence for the Mathematical Analysis of Cellular Systems. ARC Centre of Excellence for the Mathematical Analysis of Cellular Systems. The ARC Centre for the Mathematical Analysis of Cellular Systems aims to deliver the mathematics required to compute life. The Centre will deliver innovation in computational and mathematical biology and establish in silico biology alongside in vivo and in vitro biology. These models will allow us to understand the complexity of life at the cellu ....ARC Centre of Excellence for the Mathematical Analysis of Cellular Systems. ARC Centre of Excellence for the Mathematical Analysis of Cellular Systems. The ARC Centre for the Mathematical Analysis of Cellular Systems aims to deliver the mathematics required to compute life. The Centre will deliver innovation in computational and mathematical biology and establish in silico biology alongside in vivo and in vitro biology. These models will allow us to understand the complexity of life at the cellular level and enable new ways of combining diverse and heterogenous data. This will allow us to understand the mechanisms underlying cellular behaviour, and to apply rational design engineering methods in order to control the dynamics of biological systems. Read moreRead less
Special Research Initiatives - Grant ID: SR0354683
Funder
Australian Research Council
Funding Amount
$10,000.00
Summary
Ocean Discovery Network. The ODN will focus research on Australia's vast marine jurisdiction by:
1. Providing a forum for developing coordinated marine research enterprises in the National Research Priority areas of biodiversity, exploitation of resources, seaway security and climate.
2. Developing innovative international research and providing a mechanism for involvement in international science programs
3. Advancing research capabilities between national and international ocean scientist ....Ocean Discovery Network. The ODN will focus research on Australia's vast marine jurisdiction by:
1. Providing a forum for developing coordinated marine research enterprises in the National Research Priority areas of biodiversity, exploitation of resources, seaway security and climate.
2. Developing innovative international research and providing a mechanism for involvement in international science programs
3. Advancing research capabilities between national and international ocean scientists with web-based data-exchange services and links to global databases
4. Facilitating the transfer of research skills to young investigators
5. Maximising multidisciplinary use of Australian ocean science capacity, particularly the National Facility Research Vessel and the RSV Aurora Australis
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ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the ....ARC Centre for Kangaroo Genome. In this Australian-led Kangaroo Genome Project, we will map and characterize the tammar wallaby genome at the molecular level. Marsupial genomes are uniquely valuable because they provide comparisons that reveal new human genes, regulatory sequences and marsupial-specific genes. These will deliver new products and information useful for medicine, industry, agriculture and conservation. We will construct integrated genetic and physical maps of the genome, clone the whole genome as large inserts in BAC vectors, and build a "golden path" with minimal overlap. We will construct libraries of expressed genes from tammar tissues and array them for use in analysing gene expression.Read moreRead less
5D Imaging Flow Cytometry for in vivo Quantification of Biological Fluids. Rapid and accurate quantification of live biological fluid properties at sub-cellular and molecular levels forms the bedrock of biofluidic sciences. Majority of the biofluidic devices rely on quantifying biological fluids after its removal from the body in an in vitro Flow Cytometer (FC). FC faces many caveats i.e. biological degradation and small volume etc. In this project, we shall engineer the first in vivo 5D imaging ....5D Imaging Flow Cytometry for in vivo Quantification of Biological Fluids. Rapid and accurate quantification of live biological fluid properties at sub-cellular and molecular levels forms the bedrock of biofluidic sciences. Majority of the biofluidic devices rely on quantifying biological fluids after its removal from the body in an in vitro Flow Cytometer (FC). FC faces many caveats i.e. biological degradation and small volume etc. In this project, we shall engineer the first in vivo 5D imaging flow cytometer (5D IFC) capable of continuous assessment of potentially entire blood volume in a living mice without removing fluid out of the body. The project represents a major advancement beyond any existing flow cytometer and overcome the engineering limits of state-of-art laser scanning imaging devices.Read moreRead less
Future Keepers: impacts of climate change on ecosystem function providers. The aim of this project is to predict how key ecosystem service providers may change under resource limitation and thermal stress. The project seeks to assess how common species respond to climatic fluctuations and resource limitations when competing for resources in familiar and novel environments along six biogeographic transects throughout Australia. In combination with hypothesis-driven field, laboratory and transplan ....Future Keepers: impacts of climate change on ecosystem function providers. The aim of this project is to predict how key ecosystem service providers may change under resource limitation and thermal stress. The project seeks to assess how common species respond to climatic fluctuations and resource limitations when competing for resources in familiar and novel environments along six biogeographic transects throughout Australia. In combination with hypothesis-driven field, laboratory and transplant experiments, citizen science will be used to create a longitudinal data set of the constraints put on dominant and functionally important species. The project also seeks to enable more robust forecasting of biological responses to environmental change by integrating both empirical and theoretical capabilities.Read moreRead less
Sensory integration in the whisker pathway: cortical transformations and the neuronal mechanisms that underlie decision confidence. How does the brain use information collected by sensory systems to make decisions? This study combines behavioural experiments with neuronal recording from various brain regions to understand the neuronal mechanisms that integrate sensory signals to generate representations and guide the appropriate behavioural action.