Alphaherpesvirus recombination: safety implications for attenuated Herpesvirus vaccines. Under certain conditions some herpesviruses, including mild vaccine strains, can recombine to generate virulent viruses. Following findings that this occurred naturally between Australian poultry vaccines, with devastating results, this project will study natural herpesvirus recombination with the aim of allowing vaccines to be used more safely.
Imperfect vaccination drives herpesvirus evolution through recombination. Vaccines are used to help control disease caused by herpesviruses in animals, but some vaccination programs may drive the evolution and spread of herpesviruses with increased fitness (transmissibility, replication and virulence) through recombination. This project aims to study an important avian herpesvirus (infectious laryngotracheitis virus) in the natural host (poultry) to gain fundamental knowledge of how vaccination ....Imperfect vaccination drives herpesvirus evolution through recombination. Vaccines are used to help control disease caused by herpesviruses in animals, but some vaccination programs may drive the evolution and spread of herpesviruses with increased fitness (transmissibility, replication and virulence) through recombination. This project aims to study an important avian herpesvirus (infectious laryngotracheitis virus) in the natural host (poultry) to gain fundamental knowledge of how vaccination programs influence the emergence of diverse recombinant viruses, and identify which types of vaccination programs are best at preventing the emergence of fitter and more virulent viruses. The results are expected to inform vaccination practices to allow more effective control of these viruses in poultry and other animals.Read moreRead less
Role of Pasteurella surface polysaccharides in pathogenesis and immunity. Livestock infections cause major economic losses worldwide. The bacterium Pasteurella multocida causes multiple diseases in a range of livestock, including hemorrhagic septicaemia in cattle and fowl cholera in poultry. Two surface polysaccharide structures, capsule and lipopolysaccharide, are crucial for P. multocida to cause disease. Our data indicate that varying the amount/content of these structures also affects vaccin ....Role of Pasteurella surface polysaccharides in pathogenesis and immunity. Livestock infections cause major economic losses worldwide. The bacterium Pasteurella multocida causes multiple diseases in a range of livestock, including hemorrhagic septicaemia in cattle and fowl cholera in poultry. Two surface polysaccharide structures, capsule and lipopolysaccharide, are crucial for P. multocida to cause disease. Our data indicate that varying the amount/content of these structures also affects vaccine performance. This project aims to identify how the production of these P. multocida structures are controlled and if changes to these structures affect its ability to infect different animals/birds. Using this information, the project aims to develop state-of-the-art livestock vaccines with superior disease coverage.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
How do kangaroo herpesviruses jump to new host species? . This project aims to study alphaherpesviruses of kangaroos and other marsupials. These viruses cause outbreaks of severe disease in captive populations of marsupials when they are transmitted from natural hosts to new host species, but these cross-species transmission events are poorly understood. This project aims to study these viruses, and their capacity for cross-species transmission, using new approaches that consider herpesviruses a ....How do kangaroo herpesviruses jump to new host species? . This project aims to study alphaherpesviruses of kangaroos and other marsupials. These viruses cause outbreaks of severe disease in captive populations of marsupials when they are transmitted from natural hosts to new host species, but these cross-species transmission events are poorly understood. This project aims to study these viruses, and their capacity for cross-species transmission, using new approaches that consider herpesviruses as dynamic, mixed populations of viruses. This project also aims to develop novel, practical, and accessible vaccines to prevent disease. Benefits are expected to arise through prevention of disease in captive marsupial populations, including benefits for conservation efforts and for Australian tourism.
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Phase-variable epigenetic regulators in bacterial veterinary pathogens. This project aims to identify phasevarion regulated genes in the major bacterial swine pathogens Streptococcus suis and Actinobacillus pleuropneumoniae. Both species contain randomly switching epigenetic regulators that control expression of multiple genes by epigenetic mechanisms. Identifying phasevarion controlled genes will inform and direct future vaccine development for important livestock species.
Novel Babesia proteins and their roles in the pathogenesis of tick fever. This project aims at gaining a deep understanding of the biology of Babesia parasites and how they cause tick fever in cattle. The project expects to discover novel parasite proteins involved in the development and persistence of tick fever and identify their functional role in infection. The main expected outcome is the discovery of parasite proteins that are critical for infection and pathogenesis of cattle tick fever. T ....Novel Babesia proteins and their roles in the pathogenesis of tick fever. This project aims at gaining a deep understanding of the biology of Babesia parasites and how they cause tick fever in cattle. The project expects to discover novel parasite proteins involved in the development and persistence of tick fever and identify their functional role in infection. The main expected outcome is the discovery of parasite proteins that are critical for infection and pathogenesis of cattle tick fever. The findings will contribute to the development of future novel vaccines to control tick fever, with significant economic benefits for the beef and dairy industries worldwide.Read moreRead less
Structural Characterisation of the Type IX Secretion System. The Type IX Secretion System present in diverse bacteria of veterinary, agricultural, environmental and industrial importance enables effector proteins to be secreted and attached to the cell surface where they contribute to disease pathogenesis or degrade biopolymers of commercial interest. This project aims to determine the structure and assembly mechanism of this complex secretion nanomachine comprising 15 different proteins using s ....Structural Characterisation of the Type IX Secretion System. The Type IX Secretion System present in diverse bacteria of veterinary, agricultural, environmental and industrial importance enables effector proteins to be secreted and attached to the cell surface where they contribute to disease pathogenesis or degrade biopolymers of commercial interest. This project aims to determine the structure and assembly mechanism of this complex secretion nanomachine comprising 15 different proteins using state of the art microscopy. Knowledge of the structure will greatly enhance our understanding of secretion mechanisms and our ability to both inhibit the system to treat disease in animals or manipulate the system for industrial applications providing future economic and environmental benefits to our nation.Read moreRead less
A next-generation whole parasite bovine Babesia vaccine. . In Australia, Babesia parasites cause most of the severe and often fatal cases of cattle-tick fever, a globally significant tick-borne disease. It can be prevented by a live-attenuated parasite vaccine which has critical limitations of a 4-day shelf-life and risk of severe disease if administered to adult cattle. This project aims to evaluate in cattle a novel whole parasite Babesia bovis vaccine that cannot cause disease and can be pres ....A next-generation whole parasite bovine Babesia vaccine. . In Australia, Babesia parasites cause most of the severe and often fatal cases of cattle-tick fever, a globally significant tick-borne disease. It can be prevented by a live-attenuated parasite vaccine which has critical limitations of a 4-day shelf-life and risk of severe disease if administered to adult cattle. This project aims to evaluate in cattle a novel whole parasite Babesia bovis vaccine that cannot cause disease and can be preserved as an off-the-shelf product without losing efficacy. The expected outcome is a significantly improved vaccine for a major infectious disease that affects primary food production. As the disease imposes a major economic burden, it will have great benefit for the Australian livestock industry.
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Poly(amino acids) as immune stimulators. This project aims to develop nanoparticles built from natural hydrophobic amino acids as an immune stimulatory delivery system for peptide antigens. Currently available immune stimulants (adjuvants) are often toxic and/or are poorly chemically defined fragments of bacteria or toxins and vary from batch-to-batch. New adjuvants are in high demand; especially to facilitate the use of optimal, but weakly immunogenic, peptide antigens. It is expected that the ....Poly(amino acids) as immune stimulators. This project aims to develop nanoparticles built from natural hydrophobic amino acids as an immune stimulatory delivery system for peptide antigens. Currently available immune stimulants (adjuvants) are often toxic and/or are poorly chemically defined fragments of bacteria or toxins and vary from batch-to-batch. New adjuvants are in high demand; especially to facilitate the use of optimal, but weakly immunogenic, peptide antigens. It is expected that the proposed project will develop a novel efficient, safe and notably biodegradable self-adjuvanting delivery system that can be fully customised to match an antigen of choice. This foundational research should provide important advances for commercial immune stimulatory applications.Read moreRead less