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
Vaccine against leptospirosis. This project will utilise the information from the determination of the complete genome sequence of Leptospira borgpetersenii serovar Hardjobovis at Monash University. Bioinformatics analysis will be used to allow a global approach to identify all putative vaccine antigens which will be cloned, expressed and purified and their protective capacity investigated.
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
Pathogenesis, regulation and genomics of the ovine footrot pathogen, Dichelobacter nodosus. Footrot is one of the most economically significant diseases of sheep in Australia. The aim of this project is to develop a detailed understanding of how the bacterium that causes this infection is able to infect the sheep hoof and result in clinical disease. The complete sequence of the genome of the causative bacterium will be determined, enabling us to deduce its genetic potential. The completed projec ....Pathogenesis, regulation and genomics of the ovine footrot pathogen, Dichelobacter nodosus. Footrot is one of the most economically significant diseases of sheep in Australia. The aim of this project is to develop a detailed understanding of how the bacterium that causes this infection is able to infect the sheep hoof and result in clinical disease. The complete sequence of the genome of the causative bacterium will be determined, enabling us to deduce its genetic potential. The completed project will significantly advance fundamental knowledge of the disease process and will lead to the development of improved methods for the control of the disease, with concomitant cost savings to Australian primary industry.Read moreRead less
Proteomics and vaccine development in swine dysentery. Swine dysentery is an infectious disease of significant economic importance caused by Brachyspira hyodysenteriae. There is no effective vaccine available. This project will combine modern techniques in microbial genomics and proteomics to identify outer membrane proteins of B. hyodysenteriae and evaluate their role as candidate vaccine antigens.
Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastro ....Dissociation of a Tetrameric Enzyme with Interface-Targeted Peptides. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics and an equally urgent need to characterise new antibiotic targets. One such target is dihydrodipicolinate synthase (DHDPS) which catalyses the critical step in lysine and cell wall biosynthesis in bacteria. This proposal aims to generate new drugs targeting DHDPS for effective and rapid treatment of bacterial infections, including gastroenteritis. Recent statistics show that over 5 million Australians suffer from gastroenteritis each year and hospitalisation for this infection is nearly seven times higher for indigenous than non-indigenous children. Accordingly, this research has the potential to assure a healthier future for millions of Australians.Read moreRead less
Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to tr ....Inhibitors of meso-diaminopimelic acid (meso-DAP) and lysine biosynthesis: targeting dihydrodipicolinate synthase. With antibiotic resistance on the rise, there is an urgent need to develop new antibiotics with novel modes of action. This project aims to generate new drug candidates that target dihydrodipicolinate synthase (DHDPS) - the first enzyme in the synthesis of the bacterial cell wall - using a triple-pronged approach. This novel approach will allow for the development of new drugs to treat a range of pathogenic bacteria, including "Golden Staph".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
Bacterial vesicles transport their bioactive cargo to the host nucleus. This project aims to investigate how bacterial membrane vesicles transport their cargo to the nucleus of cells and its impact on host cell functions. Bacteria use membrane vesicles as a means of communication with the host, but the full extent of their effects on host cells has yet to be fully elucidated. This project expects to generate new knowledge in the field using cutting-edge imaging and molecular biology approaches. ....Bacterial vesicles transport their bioactive cargo to the host nucleus. This project aims to investigate how bacterial membrane vesicles transport their cargo to the nucleus of cells and its impact on host cell functions. Bacteria use membrane vesicles as a means of communication with the host, but the full extent of their effects on host cells has yet to be fully elucidated. This project expects to generate new knowledge in the field using cutting-edge imaging and molecular biology approaches. The work should provide significant benefits, particularly towards the development of membrane vesicles in gene therapy, gene editing and other applications. Read moreRead less
Characterising O-linked glycosylation across Burkholderia. Protein glycosylation, the chemical addition of sugars to proteins, enables the augmentation of protein properties. Across the Burkholderia genus we have shown O-linked glycosylation is both conserved as well as essential for bacterial fitness. Yet, we have little understanding of how glycosylation modulates the proteome of this genus. This project aims to characterise the glycoproteomes of Burkholderia species and track the impact of gl ....Characterising O-linked glycosylation across Burkholderia. Protein glycosylation, the chemical addition of sugars to proteins, enables the augmentation of protein properties. Across the Burkholderia genus we have shown O-linked glycosylation is both conserved as well as essential for bacterial fitness. Yet, we have little understanding of how glycosylation modulates the proteome of this genus. This project aims to characterise the glycoproteomes of Burkholderia species and track the impact of glycosylation on both the proteome and protein stability. By understanding how glycosylation shapes the proteome we will gain a greater understanding of the role of bacterial glycosylation in Burkholderia physiology as well as how we may better utilise microbial glycosylation for glycoprotein production.Read moreRead less