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.
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
The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Mic ....The Fine Tuned Physiology of Microaerophilic Gastric Spirilla. The aim of the project is to understand the molecular basis of fundamental properties of the physiology of enterogastric spiral bacteria of the genera Campylobacter and Helicobacter. The characteristics of these obligate microaerophiles which will be investigated are their aerobic respiratory chains, the special metabolites and enzymes involved in thiol-disulphide redox balance, and their essential requirement for carbon dioxide. Microaerobes include some bacteria, archea and protozoa. Realisation of the widespread habitats and importance of microaerophiles, has led recently to a vigorous interest in understanding their physiology. Knowledge of the basic properties of microaerophily has potential applications to Environmental Microbiology, Agriculture, Industrial Microbiology, Veterinary Science and Medicine.Read moreRead less
How Bacteria Fold Virulence Factors to Cause Disease. Bacteria use folding enzymes to assemble proteins essential for cell integrity and pathogenicity. These foldases include the Disulphide bridge proteins, which catalyse the introduction of disulfide bonds. This project will study two important human pathogens, Salmonella Typhimurium and uropathogenic Escherichia coli, to address the fundamental and poorly understood questions of diversity of Dsb networks across bacterial pathogens and the role ....How Bacteria Fold Virulence Factors to Cause Disease. Bacteria use folding enzymes to assemble proteins essential for cell integrity and pathogenicity. These foldases include the Disulphide bridge proteins, which catalyse the introduction of disulfide bonds. This project will study two important human pathogens, Salmonella Typhimurium and uropathogenic Escherichia coli, to address the fundamental and poorly understood questions of diversity of Dsb networks across bacterial pathogens and the role of these foldases in virulence. The research will reveal how bacterial virulence factors are folded, identify novel targets for therapeutic intervention and provide the basis for structure-based design on new antimicrobials in the future. Read moreRead less
A microscopical examination of curdlan production by an Agrobacterium sp. We will investigate the secretion of the insoluble polysaccharide curdlan, a (1,3)-beta-glucan, from the surfaces of Agrobacterium cells and the assembly of the individual polysaccharide chains into microfibrils. Using state-of-the-art techniques in time lapse and electron microscopy we will compare the images of wild type curdlan-producing cells with those of mutants impaired in the production of curdlan. The outputs will ....A microscopical examination of curdlan production by an Agrobacterium sp. We will investigate the secretion of the insoluble polysaccharide curdlan, a (1,3)-beta-glucan, from the surfaces of Agrobacterium cells and the assembly of the individual polysaccharide chains into microfibrils. Using state-of-the-art techniques in time lapse and electron microscopy we will compare the images of wild type curdlan-producing cells with those of mutants impaired in the production of curdlan. The outputs will be information on the mechanics of curdlan production that will complement that emerging from our molecular biological and biochemical studies. These will have implications for understanding bacterial polysaccharide production in general and may have a commercial outcome in enhanced curdlan production.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
Structures to Solve Conflicts of DNA Replication and RNA Transcription. This project aims to understand how new DNA is made so quickly and without mistakes in cells that are about to divide, in spite of competition from other processes happening at the same time on the DNA that should stop or interfere with it, such as the synthesis of RNA. The project expects to use the latest available methods to uncover what the microscopic natural machines that make DNA and RNA look like, and how they compet ....Structures to Solve Conflicts of DNA Replication and RNA Transcription. This project aims to understand how new DNA is made so quickly and without mistakes in cells that are about to divide, in spite of competition from other processes happening at the same time on the DNA that should stop or interfere with it, such as the synthesis of RNA. The project expects to use the latest available methods to uncover what the microscopic natural machines that make DNA and RNA look like, and how they compete with each other for access to DNA. Potential outcomes include the identification of processes that can be compromised by small molecules that may be developed into new antibiotics. This would be of great benefit - new antibiotics are urgently needed as one approach to countering the threat of antimicrobial resistance.Read moreRead less
Ubiquinone in Giardia: Amitochondrial component in an amitochondriate parasite. Giardia intestinalis is a fascinating organism, it is one of the most primitive nucleated organisms known and is responsible for ~280 million infections annually. Ubiquinone is usually associated with mitochondrial function, however it has been found in Giardia, which lacks this organelle. Our initial studies show that in Giardia, ubiquinone plays essential roles in electron transport pathways associated with membr ....Ubiquinone in Giardia: Amitochondrial component in an amitochondriate parasite. Giardia intestinalis is a fascinating organism, it is one of the most primitive nucleated organisms known and is responsible for ~280 million infections annually. Ubiquinone is usually associated with mitochondrial function, however it has been found in Giardia, which lacks this organelle. Our initial studies show that in Giardia, ubiquinone plays essential roles in electron transport pathways associated with membrane energisation and oxidative stress management. Elucidation of these mechanisms will have a major impact on the understanding of Giardia and other anaerobic organisms as well as being of significant evolutionary and medical importance.
Read moreRead less
Regulation of proteolysis by specialised adaptor proteins. Training research scientists of the future forms an integral part of this research program and this collaboration will provide an excellent opportunity for young Australian scientists to be exposed to the very professional and competitive environment of basic research, as it exists in Germany. It will expose early career researchers to new ideas and emerging methodologies arming them with valuable skills, which they will transfer to Aust ....Regulation of proteolysis by specialised adaptor proteins. Training research scientists of the future forms an integral part of this research program and this collaboration will provide an excellent opportunity for young Australian scientists to be exposed to the very professional and competitive environment of basic research, as it exists in Germany. It will expose early career researchers to new ideas and emerging methodologies arming them with valuable skills, which they will transfer to Australia. The involvement of Prof. Turgay in the Deutsche Forschungsgemeinschaft (DFG) Priority Programme: Proteolysis in Prokaryotes also provides a unique opportunity for these young researchers to interact with several of the worlds leading scientists in the area of proteolysis, enhancing Australia's reputation at the forefront of science.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