Designing effective Gram negative bacterial vaccines. There is a need for the development of novel vaccines for use in animals and humans. This project will to address this need by studying the functions of bacterial 'blebs' as potent inducers of the host immune system and by developing these nano-sized particles for use as safe and cost-effective vaccine candidates.
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
Structural and functional alteration of red blood cells by Babesia parasites. Cattle Tick Fever caused by Babesia parasites causes significant economic loss to the Australian livestock industry. New approaches to prevent this disease are urgently needed but this requires greater knowledge of how the parasites cause disease in cattle. By identifying novel proteins involved in the disease process we will be able to make better vaccines and drugs and save the Australian livestock industry millions ....Structural and functional alteration of red blood cells by Babesia parasites. Cattle Tick Fever caused by Babesia parasites causes significant economic loss to the Australian livestock industry. New approaches to prevent this disease are urgently needed but this requires greater knowledge of how the parasites cause disease in cattle. By identifying novel proteins involved in the disease process we will be able to make better vaccines and drugs and save the Australian livestock industry millions of dollars each year.Read moreRead less
Functional genomics of large clostridial plasmids. The aims of this genomics project are to determine how large DNA elements called plasmids are able to be transferred between different strains of a bacterium that causes disease in domestic livestock. These plasmids carry genes that encode the potent protein toxins that are responsible for several diseases. To understand how these diseases are spread we must learn how the plasmids have evolved and whether they can move from bacterium to bacteriu ....Functional genomics of large clostridial plasmids. The aims of this genomics project are to determine how large DNA elements called plasmids are able to be transferred between different strains of a bacterium that causes disease in domestic livestock. These plasmids carry genes that encode the potent protein toxins that are responsible for several diseases. To understand how these diseases are spread we must learn how the plasmids have evolved and whether they can move from bacterium to bacterium. The successful completion of the project will result in a detailed understanding of genetic elements that are important mediators of several diseases of importance to Australian primary industry.Read moreRead less
The Evolution and Diversification of Apicomplexan Cell Invasion Mechanisms. Insights gained through this project, about the mechanisms of cell invasion in Apicomplexan parasites, will have far reaching implications for a number of parasites of great significance to humans and animals. Since host cell invasion is a key step in the parasite lifecycle, proteins identified here will be prime targets for novel drugs that prevent invasion or antigens that can be used as vaccines. This will be importan ....The Evolution and Diversification of Apicomplexan Cell Invasion Mechanisms. Insights gained through this project, about the mechanisms of cell invasion in Apicomplexan parasites, will have far reaching implications for a number of parasites of great significance to humans and animals. Since host cell invasion is a key step in the parasite lifecycle, proteins identified here will be prime targets for novel drugs that prevent invasion or antigens that can be used as vaccines. This will be important for developing new control strategies for diseases of global significance such as malaria or toxoplasmosis, as well as those of national importance to the food industry of Australia, including diseases like babesiosis and coccidiosis that cause significant economic loss to the livestock and poultry industries each year.Read moreRead less
An Investigation of the Structure and Conformational Stability of a Membrane Associating Protein and its Petidic Ligands. The genome of the parasite most commonly responsible for fatal malaria will be completed this year. Structural elucidations of proteins identified from these genomic data will expedite the identification and classification of proteins synthesised by the parasite that might be developed as vaccines or as targets for anti-malarial therapeutics. In this work, recent developmen ....An Investigation of the Structure and Conformational Stability of a Membrane Associating Protein and its Petidic Ligands. The genome of the parasite most commonly responsible for fatal malaria will be completed this year. Structural elucidations of proteins identified from these genomic data will expedite the identification and classification of proteins synthesised by the parasite that might be developed as vaccines or as targets for anti-malarial therapeutics. In this work, recent developments in structural biology will be employed to obtain the structure of a vaccine candidate and to identify environmental factors that influence the stability of this structure. A novel approach will be taken to determine the conformation of ligands bound to such proteins, which will provide a basis for the development of therapeutics.Read moreRead less
Regulation of local lymphocyte trafficking and its role during infection. The study of early immune responses will contribute to the development of better vaccination strategies. In particular it will contribute by helping to understand the essential differences between reactogenicity and immunogenicity and how this relates to adjuvants. Using this understanding it will be possible to develop novel adjuvants that induce appropriate immunity with minimal side effects.
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
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