Mosquito-borne viruses - how they cause disease and novel approaches to prevention. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. This project has several national benefits. It will elucidate whether there is ....Mosquito-borne viruses - how they cause disease and novel approaches to prevention. In Australia, Ross River virus (RRV) is the most common insect borne virus that affects human health. There were more than 60,000 confirmed cases of RRV between 1993 and 2008. While not fatal, the disease is responsible for significant morbidity that has both social and economic costs for the individual, their family and the community. This project has several national benefits. It will elucidate whether there is an association between RRV strain and the severity of disease and if there are human factors that affect the seriousness of symptoms. Knowledge of both of these could provide new avenues for the design of prevention and treatment strategies.Read moreRead less
Discovery of Novel Respiratory Viruses Causing Influenza-Like Illness in Healthy Australian Adults Aged 18 to 64 Years. This work will inform our understanding of the causes of acute respiratory illnesses in Australia at the present time by looking for both known and previously undiscovered respiratory viruses. Increasing the knowledge base regarding causes of disease will have downstream relevance for health policy planners seeking to assess the burden of disease due to different causes. Early ....Discovery of Novel Respiratory Viruses Causing Influenza-Like Illness in Healthy Australian Adults Aged 18 to 64 Years. This work will inform our understanding of the causes of acute respiratory illnesses in Australia at the present time by looking for both known and previously undiscovered respiratory viruses. Increasing the knowledge base regarding causes of disease will have downstream relevance for health policy planners seeking to assess the burden of disease due to different causes. Early identification and description of new diseases will allow pre-emptive evaluation of new public health threats. This information will help to ensure availability and marketability of vaccines to prevent infection.Read moreRead less
Dissecting the Parameters for the Generation of Cytotoxic T Lymphocyte Immunity. This project aims to identify mechanisms by which antigen-presenting cells, such as dendritic cells, prime CD8+ T cells to generate effector and memory populations at the molecular level. The specific intention is to identify reagents capable of licensing dendritic cells, and examine the down-stream gene products/pathways generated by these signals using microarray analyses. Such knowledge will provide new insight i ....Dissecting the Parameters for the Generation of Cytotoxic T Lymphocyte Immunity. This project aims to identify mechanisms by which antigen-presenting cells, such as dendritic cells, prime CD8+ T cells to generate effector and memory populations at the molecular level. The specific intention is to identify reagents capable of licensing dendritic cells, and examine the down-stream gene products/pathways generated by these signals using microarray analyses. Such knowledge will provide new insight into CTL generation by providing greater understanding of how multicellular systems function both at the cellular and molecular level.Read moreRead less
Imaging of immune responses to pathogens in vivo. This proposal represents an excellent opportunity for Australian science to participate in state-of-the-art research into the immune system and to be internationally competitive with the best researchers in the field. By combining advanced microscopy techniques with well developed biological models used by researchers at the University of Melbourne, this project will greatly improve our understanding of the dynamic interactions that occur betwee ....Imaging of immune responses to pathogens in vivo. This proposal represents an excellent opportunity for Australian science to participate in state-of-the-art research into the immune system and to be internationally competitive with the best researchers in the field. By combining advanced microscopy techniques with well developed biological models used by researchers at the University of Melbourne, this project will greatly improve our understanding of the dynamic interactions that occur between cells of the immune system during infectious diseases. The insight provided by this project will facilitate the design of better vaccines for protection against diseases, including influenza.Read moreRead less
The role of virulence factors of Clostridium difficile in food animals. Disease caused by the bacterium Clostridium difficile are a significant food production animal and public health problem in many countries. Specific animal and human public health resources have been allocated in many countries in efforts to mitigate the growing epidemics. The study proposed in this application presents a significant opportunity to learn about the virulence factors of animal strains of this bacterium about w ....The role of virulence factors of Clostridium difficile in food animals. Disease caused by the bacterium Clostridium difficile are a significant food production animal and public health problem in many countries. Specific animal and human public health resources have been allocated in many countries in efforts to mitigate the growing epidemics. The study proposed in this application presents a significant opportunity to learn about the virulence factors of animal strains of this bacterium about which very little is known. This project will lead to rationally designed preventative and treatment strategies that apply to both animals and humans, thereby impeding epidemics caused by C. difficile in Australia.Read moreRead less
Studies on peripheral T cell memory. Success in vaccination depends on the ability of the immune system to remember prior encounter with an infectious agent. This immune memory appears to work well for certain infections but not others, essentially meaning that for these diseases, effective vaccines remain unavailable. This application describes experiments based on a new leukocyte or white blood cell population that has been overlooked in studies of immune memory. The work involves identifyin ....Studies on peripheral T cell memory. Success in vaccination depends on the ability of the immune system to remember prior encounter with an infectious agent. This immune memory appears to work well for certain infections but not others, essentially meaning that for these diseases, effective vaccines remain unavailable. This application describes experiments based on a new leukocyte or white blood cell population that has been overlooked in studies of immune memory. The work involves identifying how they are formed and how they behave within the body. This work will therefore contribute to the development and production of new-generation vaccines to these so far uncontrollable infectious diseases.Read moreRead less
Development of purified antibodies that kill virus infected cells. This proposal will develop panels of purified and monoclonal antibodies that kill virus infected cells. These antibodies may show efficacy in preventing HIV infection. This is new technology that could subsequently be harnessed to protect or limit the devastating effects of chronic viruses such as HIV.
Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymera ....Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymerase. This project aims to define the inhibition mechanism and to evaluate a potential use of these compounds for antiviral drug development.Read moreRead less
The dynamics of viral latency in chronic infection. Although many acute infections can now be controlled, we still suffer from a large number of chronic infections such as HIV or herpes that cannot be eradicated. Many of these infections persist because they can lie dormant in a 'latent' state. How this latent state is established, and how long it lasts are important to understand if we want to control these infections. We have assembled a team of mathematicians, immunologists and virologists in ....The dynamics of viral latency in chronic infection. Although many acute infections can now be controlled, we still suffer from a large number of chronic infections such as HIV or herpes that cannot be eradicated. Many of these infections persist because they can lie dormant in a 'latent' state. How this latent state is established, and how long it lasts are important to understand if we want to control these infections. We have assembled a team of mathematicians, immunologists and virologists in order to study latent infection at the cellular level, and within infected monkeys. This will provide the first insights into the dynamics of latency - how these cells are produced and die - and should lead to novel approaches to controlling chronic infection.Read moreRead less
The Role of High-Frequency Antigenic Variation in The Pathogenesis of Mycoplasma infection. The main goal of the proposed project is to understand the molecular mechanisms of phase/antigenic variation and its effects on mycoplasma pathogenesis. In this context I will use the well-characterised Mycoplasma synoviae haemagglutinin, MSPA, to establish the role of its phase-variable expression in the type and extent of M. synoviae disease. Additionally, the relationship between MSPA phase variation a ....The Role of High-Frequency Antigenic Variation in The Pathogenesis of Mycoplasma infection. The main goal of the proposed project is to understand the molecular mechanisms of phase/antigenic variation and its effects on mycoplasma pathogenesis. In this context I will use the well-characterised Mycoplasma synoviae haemagglutinin, MSPA, to establish the role of its phase-variable expression in the type and extent of M. synoviae disease. Additionally, the relationship between MSPA phase variation and gene rearrangements in the MSPB-encoding gene will be elucidated. The results will contribute to our understanding of the pathogenesis of bacterial disease and of the evolution of pathogenic mechanisms in bacterial pathogens.Read moreRead less