Structural and functional investigations into a novel chemokine binding protein encoded by evolutionarily diverse alphaherpesviruses. The outcomes of this project will help control disease caused by alphaherpesviruses, including disease in livestock (horses and poultry) and wildlife (kangaroos and wallabies). This will enhance animal health and welfare and will also benefit the associated industries. Livestock industries are critically important to the Australian economy (equine and poultry indu ....Structural and functional investigations into a novel chemokine binding protein encoded by evolutionarily diverse alphaherpesviruses. The outcomes of this project will help control disease caused by alphaherpesviruses, including disease in livestock (horses and poultry) and wildlife (kangaroos and wallabies). This will enhance animal health and welfare and will also benefit the associated industries. Livestock industries are critically important to the Australian economy (equine and poultry industries annually contribute approximately $7.7 and $2.6 billion respectively to our GDP). Wildlife species are crucial to Australian ecosystems and feature in the Australian tourism industry. This project is expected to strengthen international research collaborations and further enhance Australia's reputation as a world-class leader in research and biotechnology.Read moreRead less
Equine rhinitis A virus; molecular pathogenesis and methods for control. The horse industry in Australia is primarily based in rural locations and is a major contributor to the national economy both in terms of direct economic contribution to gross domestic product and as a major employer of people in regional Australia. The research proposed in this project will improve our understanding of the pathogenesis of a virus that causes respiratory disease in horses that is related to the virus that c ....Equine rhinitis A virus; molecular pathogenesis and methods for control. The horse industry in Australia is primarily based in rural locations and is a major contributor to the national economy both in terms of direct economic contribution to gross domestic product and as a major employer of people in regional Australia. The research proposed in this project will improve our understanding of the pathogenesis of a virus that causes respiratory disease in horses that is related to the virus that causes foot and mouth disease in ruminants and swine. The technology developed during this project would have a global market.Read moreRead less
Investigation of the immunological properties of a novel adjuvant in sheep. The induction of strong immune responses without side effects is a highly desirable goal in vaccine R&D. The recently developed adjuvant DCtag utilises unique properties of dendritic cells to boost both cellular and humoral immune responses without tissue damage. This project will identify the mechanisms of immune induction of DCtag using unique properties of our sheep cannulation model. This will allow further optimisat ....Investigation of the immunological properties of a novel adjuvant in sheep. The induction of strong immune responses without side effects is a highly desirable goal in vaccine R&D. The recently developed adjuvant DCtag utilises unique properties of dendritic cells to boost both cellular and humoral immune responses without tissue damage. This project will identify the mechanisms of immune induction of DCtag using unique properties of our sheep cannulation model. This will allow further optimisation of DCtag adjuvanticity in sheep, which will then be applied to the delivery of a prototype peptide based vaccine against foot and mouth disease virus, a veterinary disease of global importance, hereby increasing Australia's leadership in biotechnology.Read moreRead less
Application of DNA vaccination to the control of gastrointestinal nematodes in livestock. Gastrointestinal nematode parasites inflict great losses in sheep and cattle and reliance on anthelmintic drugs for their control is problematic. Vaccination would provide a better alternative but has been difficult to achieve. This proposal aims to apply novel DNA vaccination strategies to the development of parasite vaccines through optimisation of DNA delivery, development of new vaccination vectors and ....Application of DNA vaccination to the control of gastrointestinal nematodes in livestock. Gastrointestinal nematode parasites inflict great losses in sheep and cattle and reliance on anthelmintic drugs for their control is problematic. Vaccination would provide a better alternative but has been difficult to achieve. This proposal aims to apply novel DNA vaccination strategies to the development of parasite vaccines through optimisation of DNA delivery, development of new vaccination vectors and modulation of immune responses by co-delivery of cytokine genes. The results of these studies will not only add a new approach to vaccine development against gastrointestinal parasites but will also contribute to our knowledge of DNA vaccination in large animals.Read moreRead less
Defining pathways that control T cell lifespan for long-term immunity. This project will investigate the cellular and molecular pathways regulating lifespan of tissue-resident memory T cells (Trm cells), a non-circulating T cell subset that play a crucial role in the frontline defence against infection. Significantly, how long Trm cells live is paramount to how long immunity is sustained. Using cutting-edge cellular and molecular techniques, the expected outcomes of this project include identifi ....Defining pathways that control T cell lifespan for long-term immunity. This project will investigate the cellular and molecular pathways regulating lifespan of tissue-resident memory T cells (Trm cells), a non-circulating T cell subset that play a crucial role in the frontline defence against infection. Significantly, how long Trm cells live is paramount to how long immunity is sustained. Using cutting-edge cellular and molecular techniques, the expected outcomes of this project include identification of the genes and processes that control lifespan. This should provide significant benefits in the basic knowledge of how longevity of immunity is regulated. This understanding will be useful for future immunotherapeutic applications, such as veterinary or human vaccines requiring maximal duration of immunityRead moreRead less
Application of in vivo electroporation to DNA immunisation. The in vivo delivery of plasmid DNA induces immune responses to the encoded protein vaccine. In large animals including humans, DNA vaccination needs to be further improved before becoming a commercial reality, at least partially due to the very low levels of expression in vivo. In vivo electroporation has proven to be an effective way to enhance the level of protein expression and increase DNA vaccine efficacy. We combine enhanced in ....Application of in vivo electroporation to DNA immunisation. The in vivo delivery of plasmid DNA induces immune responses to the encoded protein vaccine. In large animals including humans, DNA vaccination needs to be further improved before becoming a commercial reality, at least partially due to the very low levels of expression in vivo. In vivo electroporation has proven to be an effective way to enhance the level of protein expression and increase DNA vaccine efficacy. We combine enhanced in vivo expression using electroporation with the co-delivery of plasmids encoding cytokines to enhance and modulate DNA vaccine in sheep. We will apply our findings to bovine viral diarrhoea virus (BVDV), both as an animal model for humans and as an economically important diseases of livestock.Read moreRead less
Designing new generation adjuvants for allergy and parasite vaccines. Allergy vaccines have the potential to provide a permanent cure against many allergic diseases, currently affecting 20-30 per cent of people in developed countries. This project will study how allergy vaccines work and how we can improve their effectiveness and safety.
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 immuno-exosomes in innate immunity. This project aims to determine the role of exosomes (EV) in innate immunity. Exosomes are extracellular vesicles secreted by mammalian cells that have an important biological function in intercellular communication by transferring biologically active proteins, lipids, and RNAs to neighbouring or distant cells. Following exposure to a foreign organism, cells dynamically change the protein composition of the EV they secrete. While this data supports ....The role of immuno-exosomes in innate immunity. This project aims to determine the role of exosomes (EV) in innate immunity. Exosomes are extracellular vesicles secreted by mammalian cells that have an important biological function in intercellular communication by transferring biologically active proteins, lipids, and RNAs to neighbouring or distant cells. Following exposure to a foreign organism, cells dynamically change the protein composition of the EV they secrete. While this data supports a role for EV as key players in innate immunity, a full understanding of the biological relevance of these vesicles and how they serve as a cellular defence mechanism is lacking. This project will provide significant benefits such as addressing key questions in EV biology and providing new fundamental insights into a novel and poorly understood component of the innate immune response.Read moreRead less