The biogenesis of bacterial outer membranes; how bacteria build their surface membranes. The outer membrane protects probiotic bacteria in the human intestine and enables pathogenic bacteria to cause infectious diseases. We will determine bacteria build their outer membranes - outstanding training opportunities come through cutting edge technology and the development of skills not common in Australia.
Molecular insights into bacterial metal ion homeostasis and toxicity. This project aims to measure bacterial cellular metal concentrations, elucidate mechanisms cells use to adapt to changing extracellular metal concentrations, and reveal the molecular targets of metal toxicity. Metal ions are essential to all forms of life, and half of all proteins use metal ions for cellular chemical processes. However, how cells precisely balance sufficient metal ions for essential cellular chemistry without ....Molecular insights into bacterial metal ion homeostasis and toxicity. This project aims to measure bacterial cellular metal concentrations, elucidate mechanisms cells use to adapt to changing extracellular metal concentrations, and reveal the molecular targets of metal toxicity. Metal ions are essential to all forms of life, and half of all proteins use metal ions for cellular chemical processes. However, how cells precisely balance sufficient metal ions for essential cellular chemistry without accumulating a toxic excess (metal homeostasis) is poorly understood. Discovering the roles of metal ions in bacterial cells will be key to defining the chemical biology of living systems and will provide information essential to understanding how microbes adapt to changing environments.Read moreRead less
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
Investigating pathways of lipoglycan formation in the bacterial cell wall. This project aims to investigate how the complex cell walls of Mycobacteria and Corynebacteria are assembled. The project will utilise a combination of genetic, biochemical and advanced analytical approaches to investigate individual steps in the synthesis of key cell wall components and understand how the assembly of these components is coordinated with bacterial growth. Important outcomes of this research will be detail ....Investigating pathways of lipoglycan formation in the bacterial cell wall. This project aims to investigate how the complex cell walls of Mycobacteria and Corynebacteria are assembled. The project will utilise a combination of genetic, biochemical and advanced analytical approaches to investigate individual steps in the synthesis of key cell wall components and understand how the assembly of these components is coordinated with bacterial growth. Important outcomes of this research will be detailed information on processes that regulate the growth of bacteria with important biotechnology, veterinary and medical significance, as well as information on mechanisms of cell wall synthesis that may be conserved in all bacteria.Read moreRead less
Nucleomodulin effectors of the environmental pathogen Legionella. This project aims to examine the evolution of Legionella as an intracellular organism and the mechanisms by which the bacteria evade environmental predation by amoebae. Aside from the advancement of knowledge, expected outcomes of this project include a greater understanding of amoebae. This will provide significant benefits, and this knowledge may be used to develop inhibitors of amoebae growth.
Mechanism of action of a novel multifunctional bacterial secretion system. This project aims to examine the functional role of holin/lysin secretion systems in the complex lifestyles of important animal bacterial pathogens. This project will generate new knowledge in how bacteria interact with each other, the environment or their hosts through the secretion of proteins or other particles. The results of this research will provide a deeper understanding of the multifunctional roles that these un ....Mechanism of action of a novel multifunctional bacterial secretion system. This project aims to examine the functional role of holin/lysin secretion systems in the complex lifestyles of important animal bacterial pathogens. This project will generate new knowledge in how bacteria interact with each other, the environment or their hosts through the secretion of proteins or other particles. The results of this research will provide a deeper understanding of the multifunctional roles that these unusual secretion systems play and how they contribute to niche adaptation and disease. New insights will lead to identifying targets for future veterinary disease interventions or biotechnological applications.Read moreRead less
Identifying Novel Biosynthetic Pathways in Mycobacteria using DNA Microarray Technology. DNA microarrays are a powerful new bioinformatics-based technology and an ideal tool for characterising complex biosynthetic pathways since the expression of all genes in the bacterial genome can be monitored in a single experiment. In this project we aim to construct and use a DNA microarray to identify novel biosynthetic pathways in mycobacteria. Of particular interest are pathways used to create compone ....Identifying Novel Biosynthetic Pathways in Mycobacteria using DNA Microarray Technology. DNA microarrays are a powerful new bioinformatics-based technology and an ideal tool for characterising complex biosynthetic pathways since the expression of all genes in the bacterial genome can be monitored in a single experiment. In this project we aim to construct and use a DNA microarray to identify novel biosynthetic pathways in mycobacteria. Of particular interest are pathways used to create components of the highly complex and poorly characterised cell wall. Since this structure is unique in the bacterial world, we expect to identify and characterise pathways that are unique to mycobacteria.Read moreRead less
How auto-transporter proteins mediate bacterial interactions. This project aims to investigate the structure-function relationships that underpin key auto-transporter roles in bacterial cell adhesion, aggregation and biofilm formation. Auto-transporter proteins are extremely common in bacteria where they play a central role in controlling bacterial interactions with other bacteria, with human cells, and with surfaces. This project will define the molecular mechanisms underlying these processes. ....How auto-transporter proteins mediate bacterial interactions. This project aims to investigate the structure-function relationships that underpin key auto-transporter roles in bacterial cell adhesion, aggregation and biofilm formation. Auto-transporter proteins are extremely common in bacteria where they play a central role in controlling bacterial interactions with other bacteria, with human cells, and with surfaces. This project will define the molecular mechanisms underlying these processes. This will have significant benefits, such as providing the basis for the development of approaches to block auto-transporter functions that contribute to the establishment of persistent and difficult to treat bacterial infections.Read moreRead less
Investigation of a Novel Protein Implicated in Phosphate Metabolism in Bacteria. Phosphate is an important nutrient for all forms of life on Earth. A novel bacterial protein has been identified that appears to be important for the uptake or processing of phosphate, since mutants lacking the protein grow poorly inside certain cells of the human immune system (where phosphate levels are low) and in media containing low phosphate. The aims of this project are: to determine the role of the protein b ....Investigation of a Novel Protein Implicated in Phosphate Metabolism in Bacteria. Phosphate is an important nutrient for all forms of life on Earth. A novel bacterial protein has been identified that appears to be important for the uptake or processing of phosphate, since mutants lacking the protein grow poorly inside certain cells of the human immune system (where phosphate levels are low) and in media containing low phosphate. The aims of this project are: to determine the role of the protein by examining all phosphate containing molecules in our mutants; to determine its location in bacteria and functional domains; to identify other affected genes in our mutants; and, to find proteins that interact with this new protein. This project expects to demonstrate the importance of this protein in phosphate metabolism in bacteria.Read moreRead less
Unraveling autotransporter function in bacterial aggregates and biofilms. Autotransporters are a large family of bacterial proteins that play a central role in pathogenesis. They promote the formation of cell clusters and biofilms, which are mechanisms for bacterial resistance to host immune factors and antibiotics. Currently, the precise mode of action of autotransporters is unknown. This project will examine the interplay between the structure and function of key autotransporter proteins. It ....Unraveling autotransporter function in bacterial aggregates and biofilms. Autotransporters are a large family of bacterial proteins that play a central role in pathogenesis. They promote the formation of cell clusters and biofilms, which are mechanisms for bacterial resistance to host immune factors and antibiotics. Currently, the precise mode of action of autotransporters is unknown. This project will examine the interplay between the structure and function of key autotransporter proteins. It is expected that the outcomes of this research will establish how these proteins mediate aggregation and biofilm formation. It may also provide three-dimensional structures of proteins that are strongly immunogenic and may represent targets for future vaccine design, as well as identify molecules that inhibit autotransporter function.Read moreRead less