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
Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput ge ....Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput genomics. The expected outcomes will overturn our current view on enhancer evolution and reposition our understanding of how enhancers are functionally encoded in the genome. The work is an important contribution to understanding cellular complexity and species evolution with wide-ranging impact in genetics.Read moreRead less
Humane Chemical Methods for Population Management of Highly Valued Large Mammals. In many countries valued wild and feral animals are nonetheless too numerous. Their population numbers must be controlled through fertility. Examples are koalas in Australia, deer and seals in North America, cattle in India and dogs in Thailand. We aim to develop benign implants for castration based upon the gonadotrophin releasing hormone (GnRH). These implants are easily administered. The outcomes will be to ....Humane Chemical Methods for Population Management of Highly Valued Large Mammals. In many countries valued wild and feral animals are nonetheless too numerous. Their population numbers must be controlled through fertility. Examples are koalas in Australia, deer and seals in North America, cattle in India and dogs in Thailand. We aim to develop benign implants for castration based upon the gonadotrophin releasing hormone (GnRH). These implants are easily administered. The outcomes will be to protect Australia's ?green? image , worldwide market opportunities for the Australian companies involved in this application and valuable intellectual property for Macquarie. The methodology will in time allow us to apply it to the treatment of cancer.Read moreRead less
Genomic Basis of Resistance to Poisoning by Sodium Fluoroacetate (Compound 1080) in Australian Wildlife. In Australia agricultural conservation activities worth billions of dollars are protected by using sodium fluoroacetate (1080) against pest animals. Target species are Australian rabbits and foxes and New Zealand brushtail possums. Prolonged use of biocontrol agents causes genetic resistance. This occurs naturally in Western Australia in native animals living in areas with high levels of 1080 ....Genomic Basis of Resistance to Poisoning by Sodium Fluoroacetate (Compound 1080) in Australian Wildlife. In Australia agricultural conservation activities worth billions of dollars are protected by using sodium fluoroacetate (1080) against pest animals. Target species are Australian rabbits and foxes and New Zealand brushtail possums. Prolonged use of biocontrol agents causes genetic resistance. This occurs naturally in Western Australia in native animals living in areas with high levels of 1080 in native plants. As part of the Kangaroo Genome project our aim is to discover the genomic basis of this resistance. The outcomes will be improved ability to manage pest animal populations and understanding of the evolution of plant-animal interactions.Read moreRead less
The Mechanism Of HSV-1 Transport In Sensory Axons And Its Unique Assembly At The Axon Terminus
Funder
National Health and Medical Research Council
Funding Amount
$670,284.00
Summary
Herpes simplex viruses 1 and 2 cause common diseases such as genital herpes and, occasionally, neonatal deaths and encephalitis and predisposes to HIV infection. New antiviral strategies are required for resistant viruses for control. These aims will be facilitated by understanding how HSV is transported down nerves and across into skin. In this study, we will define how a key viral protein plays a major role in assembly of the virus at the tip of the nerve before it enters skin.
Elucidating the genetic basis of newly evolved metabolic functions in yeast. Elucidating the genetic basis of newly evolved metabolic functions in yeast. This project intends to research how complex metabolic pathways originate and evolve. This project will use cutting edge genome sequencing and molecular techniques to elucidate the heritable genetic basis of Baker’s yeast, which has been the selectively evolved to use xylose as a sole carbon source: something vital for second generation biofuel ....Elucidating the genetic basis of newly evolved metabolic functions in yeast. Elucidating the genetic basis of newly evolved metabolic functions in yeast. This project intends to research how complex metabolic pathways originate and evolve. This project will use cutting edge genome sequencing and molecular techniques to elucidate the heritable genetic basis of Baker’s yeast, which has been the selectively evolved to use xylose as a sole carbon source: something vital for second generation biofuel production that wild yeast cannot do. This project will combine detailed molecular characterisation of highly adapted yeast strains with a novel "molecular palaeontology" approach to trace the evolutionary process and identify functionally significant loci under selection. Detailed characterisation of this trait will accelerate the development of future yeast strains and test fundamental evolutionary theories.Read moreRead less
Pathogenesis Of Persistent Human Virus Infections Of Global Significance
Funder
National Health and Medical Research Council
Funding Amount
$6,571,328.00
Summary
The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully ....The study will investigate why humans cannot eradicate particular viruses (HIV-AIDS, cytomegalovirus and herpes simplex virus), the long term effects of these viruses and ways to improve control. Current treatments can only partly suppress the levels of these viruses, because they persist in certain parts of the body called reservoirs, only to resurge later causing disease. Thus, the overall aim of the research program is to discover the mechanisms by which these viruses are able to successfully persist within reservoirs in the human body. The research program brings together a group of 6 leading scientists and clinicians located at 3 sites in 2 Australian cities. The team is comprised of experts in the study of HIV-AIDS, cytomegalovirus and herpes simplex virus who will combine their knowledge and expertise to speed up the process of research on these viruses that are of major health importance. Studies will also utilise a number of cutting edge technologies that now make it possible to much more rapidly and precisely determine how viruses cause disease. Advances in our understanding of how viruses persist may form the basis for treatments aimed at controlling persistent infections and the serious diseases caused by these viruses.Read moreRead less
Placental nutrient transport shows how complex traits evolve. This project aims to use amino acid transport in the vertebrate placenta as a model to demonstrate how genes are recruited and modified to produce a major organ. Using an innovative combination of a new technology, selected reaction monitoring, and transcriptomic and molecular approaches, plus carefully selected Australian species pairs, this project will study the evolution of a complex trait (placental amino acid transport). The pr ....Placental nutrient transport shows how complex traits evolve. This project aims to use amino acid transport in the vertebrate placenta as a model to demonstrate how genes are recruited and modified to produce a major organ. Using an innovative combination of a new technology, selected reaction monitoring, and transcriptomic and molecular approaches, plus carefully selected Australian species pairs, this project will study the evolution of a complex trait (placental amino acid transport). The project will provide fundamental advances in our knowledge of the nutrient transport during pregnancy that is required to produce a healthy baby.Read moreRead less
Regulation of saxitoxin production in bacteria and algae. In Australia, toxic algal blooms have had a devastating impact on marine and freshwater resources. In collaboration with a biotechnology company, this project will develop exciting new methods based on information regarding the genetics of the toxin, to monitor and potentially mitigate the effects of algal blooms on water supplies and aquaculture industries. We will use this method to determine the impact of light and salinity in regulati ....Regulation of saxitoxin production in bacteria and algae. In Australia, toxic algal blooms have had a devastating impact on marine and freshwater resources. In collaboration with a biotechnology company, this project will develop exciting new methods based on information regarding the genetics of the toxin, to monitor and potentially mitigate the effects of algal blooms on water supplies and aquaculture industries. We will use this method to determine the impact of light and salinity in regulating toxin production in cyanobacteria and algae.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE180100306
Funder
Australian Research Council
Funding Amount
$365,058.00
Summary
Does spurious maternal-fetal signalling support the evolution of a placenta. This project aims to test a model that explains how the placenta has evolved as a new organ more than 100 times in fishes, reptiles, and mammals including our own ancestors. The project will assess whether regulatory components of the placenta evolve as a result of spurious maternal-fetal signalling following egg retention and eggshell loss in viviparous reptiles. Expected outcomes of this project include a new understa ....Does spurious maternal-fetal signalling support the evolution of a placenta. This project aims to test a model that explains how the placenta has evolved as a new organ more than 100 times in fishes, reptiles, and mammals including our own ancestors. The project will assess whether regulatory components of the placenta evolve as a result of spurious maternal-fetal signalling following egg retention and eggshell loss in viviparous reptiles. Expected outcomes of this project include a new understanding of how complex organs originate and evolve in animals. This will benefit society through a broader depth of understanding of our own evolutionary history and provides a framework for future studies to investigate the origin and evolution of organs more broadly in animals.Read moreRead less