Virulence determinants influencing re-emergence of a complex RNA virus. This project intends to examine the effects that specific genes in naturally occurring recombinants have on their capacity to cause disease and spread between chickens. Coronaviruses are major pathogens of domestic animals throughout the world. Recurrent re-emergence of the coronavirus of chickens, infectious bronchitis virus, has been associated with recombination between wild type viruses and vaccine viruses, but the facto ....Virulence determinants influencing re-emergence of a complex RNA virus. This project intends to examine the effects that specific genes in naturally occurring recombinants have on their capacity to cause disease and spread between chickens. Coronaviruses are major pathogens of domestic animals throughout the world. Recurrent re-emergence of the coronavirus of chickens, infectious bronchitis virus, has been associated with recombination between wild type viruses and vaccine viruses, but the factors influencing this, and in particular the selective advantages genes from vaccine viruses confer on these recombinants, are unknown. The ultimate aim of the project is to identify both novel vaccines and alternative management strategies that might reduce the frequency of re-emergence of this virus and other coronaviruses.Read moreRead less
Avoiding the immune response: lessons from 'simple' bacteria. Some of the most important bacterial diseases of domestic animals are caused by mycoplasmas. Improved control of these diseases would significantly improve agricultural productivity by reducing losses associated with reduced feed conversion efficiency and increased susceptibility to other diseases, as well as improve animal welfare and public health, by reducing the need for antibiotic therapy to control these diseases in food produci ....Avoiding the immune response: lessons from 'simple' bacteria. Some of the most important bacterial diseases of domestic animals are caused by mycoplasmas. Improved control of these diseases would significantly improve agricultural productivity by reducing losses associated with reduced feed conversion efficiency and increased susceptibility to other diseases, as well as improve animal welfare and public health, by reducing the need for antibiotic therapy to control these diseases in food producing animals.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
Microcrystallography of spheroids: crystalline armours of insect viruses. The proposed project will provide fundamental insights into the organisation of ultra-stable armours protecting insect viruses. This will open novel avenues for the development of highly efficient and specific bioinsectides as well as innovative tools such as natural microparticles for improved vaccines.
The techniques used in this project are at the frontier of imaging techniques and will establish a national expertise i ....Microcrystallography of spheroids: crystalline armours of insect viruses. The proposed project will provide fundamental insights into the organisation of ultra-stable armours protecting insect viruses. This will open novel avenues for the development of highly efficient and specific bioinsectides as well as innovative tools such as natural microparticles for improved vaccines.
The techniques used in this project are at the frontier of imaging techniques and will establish a national expertise in X-ray micro-crystallography. This will contribute to the optimal use of the $8-million microfocus beamline of the newly built Australian Synchrotron enabling breakthroughs such as the structures of membrane receptors for hormone and neurotransmitter with major implications for drug development.Read moreRead less
Unravelling small RNA regulatory networks to target and control bacteria. Small RNA (sRNA) molecules are critical regulators of bacterial gene expression. These molecules control important phenotypes in the Gram-negative veterinary pathogen Pasteurella multocida. This project aims to identify the range of P. multocida sRNAs and to show how expression of these molecules changes under various growth conditions. Specifically, this project endeavours: to identify the mRNA targets of the sRNAs; to id ....Unravelling small RNA regulatory networks to target and control bacteria. Small RNA (sRNA) molecules are critical regulators of bacterial gene expression. These molecules control important phenotypes in the Gram-negative veterinary pathogen Pasteurella multocida. This project aims to identify the range of P. multocida sRNAs and to show how expression of these molecules changes under various growth conditions. Specifically, this project endeavours: to identify the mRNA targets of the sRNAs; to identify the mechanisms of sRNA-mRNA interaction; to build systems-biology models that describe the sRNA regulatory circuits; to design inhibitors capable of disrupting critical sRNA-mRNA interactions; and to use the new inhibitors to modulate specific phenotypes. The ability to precisely manipulate sRNA regulatory circuits could allow fine control of bacterial phenotypes and could be widely applicable.Read moreRead less
A comprehensive analysis of the outer membrane, surface exposed and secreted proteome of Pasteurella multocida. Pasteurella multocida is the causative agent of a range of animal diseases. The molecular mechanisms of P. multocida pathogenesis are poorly understood and the current vaccines generally ineffective. We will identify all P. multocida outer membrane, surface exposed and secreted proteins expressed during natural infection, or under conditions which mimic natural infection, by a global p ....A comprehensive analysis of the outer membrane, surface exposed and secreted proteome of Pasteurella multocida. Pasteurella multocida is the causative agent of a range of animal diseases. The molecular mechanisms of P. multocida pathogenesis are poorly understood and the current vaccines generally ineffective. We will identify all P. multocida outer membrane, surface exposed and secreted proteins expressed during natural infection, or under conditions which mimic natural infection, by a global proteomics approach. We believe that secreted proteins and those found on the outer surface of the bacterial cell are likely to be crucial virulence determinants. The expected outcomes are the identification of a number of candidate vaccine antigens and an enhanced understanding of Pasteurella pathogenesis.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
Linking immunomodulation and latency in alphaherpesvirus infection. Herpesviruses cause major diseases in humans and all domestic animal species. Latency forms a significant part of the evolutionary success of herpesviruses, by enabling transmission of the virus throughout the lifetime of the host. Our work has shown that an alphaherpesvirus protein can divert the host’s immune response to become more antibody-mediated and less T cell-mediated. This study explores the consequences of this immune ....Linking immunomodulation and latency in alphaherpesvirus infection. Herpesviruses cause major diseases in humans and all domestic animal species. Latency forms a significant part of the evolutionary success of herpesviruses, by enabling transmission of the virus throughout the lifetime of the host. Our work has shown that an alphaherpesvirus protein can divert the host’s immune response to become more antibody-mediated and less T cell-mediated. This study explores the consequences of this immune diversion, and examines whether this reduced T cell response enables the development of latent infections. Disrupting the virus-host balance by alterations to this conserved viral protein will enable novel approaches to controlling these economically significant viruses.Read moreRead less