Inhibition Of Cellcell Actin-based Motility During Poxvirus Infection By The Kinase Inhibitor Glivec
Funder
National Health and Medical Research Council
Funding Amount
$92,950.00
Summary
Although smallpox, one of the deadliest human pathogens, was eradicated in 1980, the current global climate has resulted in fears that smallpox may be used as a biological weapon. Unfortunately the smallpox vaccine poses a serious health hazard to certain people. We have shown that Glivec, a drug used to treat cancer, has potent anti-viral affects on poxvirus replication. This project will test the effectiveness of Glivec in treating smallpox in an animal model and study how it acts.
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.
What is killing the honeybees? The role of RNA viruses. This project aims to determine if the Varroa mite, the most important parasite of honeybees, selects for virulent strains of RNA viruses. Before Varroa’s inevitable arrival in Australia, this project will disentangle the effect of Varroa and the bees’ immune system on the evolution of virulence of bee viruses. Australia’s honeybees are Varroa-naïve and don’t carry virulent viruses. There is a known association between Varroa and colonies dy ....What is killing the honeybees? The role of RNA viruses. This project aims to determine if the Varroa mite, the most important parasite of honeybees, selects for virulent strains of RNA viruses. Before Varroa’s inevitable arrival in Australia, this project will disentangle the effect of Varroa and the bees’ immune system on the evolution of virulence of bee viruses. Australia’s honeybees are Varroa-naïve and don’t carry virulent viruses. There is a known association between Varroa and colonies dying from viruses; however, it is not known what is cause and effect. This project will clarify Varroa’s exact role in the evolution of virulence in RNA viruses. The intended outcome is increased knowledge allowing the design of an effective treatment to prevent the death of honeybee colonies.Read moreRead less
Viral And Host Cell Gene Expression During The Establishment And Maintenance Phases Of Human Cytomegalovirus Latency
Funder
National Health and Medical Research Council
Funding Amount
$149,250.00
Summary
Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and ....Human cytomegalovirus (CMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing CMV disease. Like other herpesviruses, after initial infection CMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. The overall aim of these studies is to provide a much better understanding of how CMV latency is established and maintained, with the ultimate goal of making advances for the design of anti-viral therapies to disrupt these processes. This project has three major components: Firstly, we aim to identify and characterise viral gene expression during the establishment of latency and these findings will have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during the establishment and maintenance phases of latency. Thirdly, we will apply microarray technologies to determine how human cell genes are altered in response to the expression of individual viral genes that are active during the latent phase of infection.Read moreRead less
Integrating nutritional immunology. What an organism eats affects both its susceptibility to disease and the community of beneficial microorganisms living within its gut. This project will study how nutrition, immunity and the flora of the gut interact, and whether hosts are able to select a diet that optimises their immune response and gut flora in the face of disease challenges.
Imaging The Hepatitis C Virus Life Cycle In Real-time
Funder
National Health and Medical Research Council
Funding Amount
$477,504.00
Summary
Hepatitis C virus (HCV) is a serious viral pathogen that causes significant liver disease. This proposal plans to examine how two proteins from the HCV, core and NS5A, interact with host proteins and pathways to facilitate viral replication and release of HCV; two processes that are poorly understood. Specifically we will tag viral proteins to allow us to investigate the HCV life cycle in living cells and determine the role of core and NS5A in facilitating HCV replication. This proposal may unco ....Hepatitis C virus (HCV) is a serious viral pathogen that causes significant liver disease. This proposal plans to examine how two proteins from the HCV, core and NS5A, interact with host proteins and pathways to facilitate viral replication and release of HCV; two processes that are poorly understood. Specifically we will tag viral proteins to allow us to investigate the HCV life cycle in living cells and determine the role of core and NS5A in facilitating HCV replication. This proposal may uncover novel therapeutic strategies to combat HCV.Read moreRead less
Evolutionary history and impact of adeno-associated viruses in Australia. Recently accrued evidence identifies Australia as an ideal closed-model system in which to elucidate the evolutionary history of a group of non-pathogenic viruses, known as adeno-associated viruses (AAVs). This project aims to trace back the evolutionary history of AAVs for tens of millions of years via molecular fossil imprints left behind by ancient viral invasions of Australian marsupial genomes. Concurrently, the poten ....Evolutionary history and impact of adeno-associated viruses in Australia. Recently accrued evidence identifies Australia as an ideal closed-model system in which to elucidate the evolutionary history of a group of non-pathogenic viruses, known as adeno-associated viruses (AAVs). This project aims to trace back the evolutionary history of AAVs for tens of millions of years via molecular fossil imprints left behind by ancient viral invasions of Australian marsupial genomes. Concurrently, the potential impact that these viral invasions had on the evolutionary development of their ancestral hosts will be investigated. This could facilitate previously unattainable insights into both AAV and marsupial evolution, with broader implications relevant to the advancement of the fields of virology and mammalian evolution.Read moreRead less
An interdisciplinary approach to host-pathogen interactions in infection. This project aims to understand the molecular and cellular interactions between host and parasite, as well as providing a quantitative framework for analysing infection dynamics in other systems. Infection involves a complex interaction between the host and the parasite, which is very dynamic and therefore difficult to study by traditional sampling and analysis approaches. This project has combined mathematical modelling w ....An interdisciplinary approach to host-pathogen interactions in infection. This project aims to understand the molecular and cellular interactions between host and parasite, as well as providing a quantitative framework for analysing infection dynamics in other systems. Infection involves a complex interaction between the host and the parasite, which is very dynamic and therefore difficult to study by traditional sampling and analysis approaches. This project has combined mathematical modelling with a novel experimental protocol to allow the study of kinetics of parasite replication in vivo. Expected outcomes will provide significant benefits, such as new avenues for vaccination and immune intervention.Read moreRead less
Altering host-parasite interactions through wildlife conservation strategies. Disease outbreaks are heightened in endangered animals but strategies used to conserve these species often increase risk of disease; nowhere is this more critical than in species recovery programs. The project will study disease in a recovery program to improve conservation practice and protect Australia's wildlife, ensuring our ecosystems are sustained.
Analysis Of Viral And Cellular Gene Expression During Human Cytomegalovirus Latent Infection Of Hematopoietic Cells
Funder
National Health and Medical Research Council
Funding Amount
$407,545.00
Summary
Human cytomegalovirus (HCMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing HCMV disease. Like other herpesviruses, after initial infection HCMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body a ....Human cytomegalovirus (HCMV) is a herpesvirus which infects a majority of the population. HCMV is a significant cause of serious, life-threatening disease in neonates and in people who are immunosuppressed. Transplant recipients such as bone marrow, kidney and heart transplant patients are particularly at risk of developing HCMV disease. Like other herpesviruses, after initial infection HCMV can establish a life-long latent infection. During latency, the virus remains dormant in the human body and no infectious virus is made. However, when conditions are right the virus can awaken (ie reactivate) from its latent state, producing new infectious virus and disease. It is in immunosuppressed individuals such as transplant patients that viral latency and reactivation are of most medical concern, yet viral latency remains very poorly understood. This project has three major components. Firstly, we aim to continue studies which are defining what viral genes are active (ie expressed) during latent infection. Identification of these genes and determination of how they function may have profound implications to our understanding of latency. Secondly, we will examine how human cells are affected when they become latently infected. A new and exciting technology called DNA microarray now makes it possible to examine the expression of many thousands of genes in a single experiment. For the first time, we will be able to determine how the cell changes during latency and reactivation. The study of viral and cellular gene expression during latency may contribute to the development of drugs which interfere with the viruses ability to become latent or reactivate. Thirdly, we have preliminary results which suggest that latent HCMV may actively avoid detection by the immune system. In this project we also aim to determine the mechanism by which the virus interferes with the expression of molecules which are an essential component of our immune system.Read moreRead less