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
Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may ....Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may lead to the development of useful drugs to treat rotavirus infection and may reduce significant loss of life caused by this deadly virus.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
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
Functional identification of vaccine targets in pathogenic mycoplasmas. Mycoplasmas are important bacterial pathogens in domestic animals that are incompletely controlled by current vaccines. As a result current control measures for the diseases they cause rely on ongoing treatment with antibiotics. This project will aim to use functional genomics and metabolomics to determine the function of specific surface proteins of a model mycoplasma to identify targets for novel approaches to vaccines aga ....Functional identification of vaccine targets in pathogenic mycoplasmas. Mycoplasmas are important bacterial pathogens in domestic animals that are incompletely controlled by current vaccines. As a result current control measures for the diseases they cause rely on ongoing treatment with antibiotics. This project will aim to use functional genomics and metabolomics to determine the function of specific surface proteins of a model mycoplasma to identify targets for novel approaches to vaccines against these pathogens, and to then assess the potential for inclusion of these proteins in vaccines. Ultimately this will lead to improved vaccines against these important pathogens, improving agricultural productivity and reducing the use of antibiotics in intensively raised livestock.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
Harnessing innate immunity to mitigate bovine respiratory disease. Bovine Respiratory Disease (BRD) is the most significant health problem faced by the beef industry worldwide, causing economic losses of up to $40 million annually in Australia alone. This Project aims to assess an immunostimulant for its ability to induce resistance to infection with bovine respiratory viruses associated with BRD. The Project is expected to generate fundamental new knowledge in veterinary virology. Expected outc ....Harnessing innate immunity to mitigate bovine respiratory disease. Bovine Respiratory Disease (BRD) is the most significant health problem faced by the beef industry worldwide, causing economic losses of up to $40 million annually in Australia alone. This Project aims to assess an immunostimulant for its ability to induce resistance to infection with bovine respiratory viruses associated with BRD. The Project is expected to generate fundamental new knowledge in veterinary virology. Expected outcomes include scholarly publications. The Project will provide significant benefits, such as advances to fundamental knowledge, training of higher research degree students and proof-of-concept data to promote collaborations with commercial partners to develop novel treatment strategies to limit BRD.Read moreRead less