Bacterial filamentation as a survival strategy: a goldmine for the discovery of new cell division regulators. The increasing emergence of untreatable bacterial infections is a serious threat to the health of Australians. Medical advances (organ transplants, chemotherapy), increases in diabetes, and an aging population increase the risk of infections caused by bacteria that are now resistant to most available antibiotics. New classes of antibiotics are urgently needed to treat these infections. T ....Bacterial filamentation as a survival strategy: a goldmine for the discovery of new cell division regulators. The increasing emergence of untreatable bacterial infections is a serious threat to the health of Australians. Medical advances (organ transplants, chemotherapy), increases in diabetes, and an aging population increase the risk of infections caused by bacteria that are now resistant to most available antibiotics. New classes of antibiotics are urgently needed to treat these infections. This project uses a novel approach to identify the mechanisms bacterial cells use to control their growth and avoid attack by our immune system. The research will identify potential targets for the development of new, effective antibiotics to kill multi-resistant bacteria, and ensure Australia's position at the forefront of infection control.Read moreRead less
Investigating the Ability of Honey to Inhibit Bacterial Biofilms Found in Chronic Wounds. Chronic (non-healing) wounds are a serious health problem in Australia. One quarter of our institutionalized aged population have pressure ulcers. The difficulty in treating these wounds is that most contain communities of bacteria, called biofilms, that are not killed by conventional antibiotics. Special honeys from Australia and NZ that are effective in chronic wound treatment can eradicate these biofilms ....Investigating the Ability of Honey to Inhibit Bacterial Biofilms Found in Chronic Wounds. Chronic (non-healing) wounds are a serious health problem in Australia. One quarter of our institutionalized aged population have pressure ulcers. The difficulty in treating these wounds is that most contain communities of bacteria, called biofilms, that are not killed by conventional antibiotics. Special honeys from Australia and NZ that are effective in chronic wound treatment can eradicate these biofilms. This project will identify the components in honey that do this and determine how they do it, to provide a more effective chronic wound treatment. It will decrease the prevalence of these wounds in Australia and the associated personal trauma and health costs.Read moreRead less
Evolutionary and ecological complexity in an experimentally controlled environment. Understanding the capacity and mechanism of microbial evolution provides the framework for developing new strategies for preventing infectious disease. If we know how evolution works, it will be possible to hamper the capacity to evolve as a mechanism of preventing new diseases and controlling existing ones. This project will provide a mechanistic description of evolution in real time under controlled conditions. ....Evolutionary and ecological complexity in an experimentally controlled environment. Understanding the capacity and mechanism of microbial evolution provides the framework for developing new strategies for preventing infectious disease. If we know how evolution works, it will be possible to hamper the capacity to evolve as a mechanism of preventing new diseases and controlling existing ones. This project will provide a mechanistic description of evolution in real time under controlled conditions. This detailed information will be used in the education of the public and in debates about evolution. The project will also train at least five students in molecular and evolutionary microbiology, essential for facing future challenges.
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Synthesis and assembly of bacterial repeat unit polysaccharides. Bacteria make an enormous range of surface polysaccharides. The complexity was first appreciated as antigenic diversity, but we now have hundreds of chemical structures and perhaps a hundred sequences of their gene clusters, but the number in nature must be many thousands. Our knowledge of gene function is growing but is not keeping up with the discovery of new sequences and structures. The aim is to determine structure and functio ....Synthesis and assembly of bacterial repeat unit polysaccharides. Bacteria make an enormous range of surface polysaccharides. The complexity was first appreciated as antigenic diversity, but we now have hundreds of chemical structures and perhaps a hundred sequences of their gene clusters, but the number in nature must be many thousands. Our knowledge of gene function is growing but is not keeping up with the discovery of new sequences and structures. The aim is to determine structure and function of key O antigen processing genes and the functions of a range of glycosyl transferases, and to use the information to generate novel gene clusters to synthesise novel polysaccharidesRead moreRead less
Elucidation of bacterial glycosylytransferase specificity. The benefits are involvement in the growth area of polysaccharide research, with potential for major industrial spin off. Polysaccharides are critical in all organisms as signalling, structural and storage compounds. Bacteria make a wide variety with extensive use of unusual sugars, some with uses from oil emulsifiers to food thickeners. The project is on the enzymes that assemble bacterial polysaccharides. We are world leaders in genet ....Elucidation of bacterial glycosylytransferase specificity. The benefits are involvement in the growth area of polysaccharide research, with potential for major industrial spin off. Polysaccharides are critical in all organisms as signalling, structural and storage compounds. Bacteria make a wide variety with extensive use of unusual sugars, some with uses from oil emulsifiers to food thickeners. The project is on the enzymes that assemble bacterial polysaccharides. We are world leaders in genetics of the gene clusters especially synthesis of the unusual sugars. We now aim to fill a major gap by determining which enzymes make which bonds, leading to options for new gene combinations and novel structures. We have a lead in research in this area and Australia gains if we maintain that lead.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
Coproantigen detection tests for diagnosis of intestinal parasitic nematode infection. The aim of this project is to develop new tests for detection of hookworm and Strongyloides, two common intestinal worm infections of humans. These tests offer the potential to replace current tests, namely stool microscopy and serodiagnosis, both of whose performance is unsatisfactory due to deficiencies in sensitivity, specificity and operator convenience. The tests will rely on monoclonal antibodies to dete ....Coproantigen detection tests for diagnosis of intestinal parasitic nematode infection. The aim of this project is to develop new tests for detection of hookworm and Strongyloides, two common intestinal worm infections of humans. These tests offer the potential to replace current tests, namely stool microscopy and serodiagnosis, both of whose performance is unsatisfactory due to deficiencies in sensitivity, specificity and operator convenience. The tests will rely on monoclonal antibodies to detect parasite products in stool. Such testing technology is amenable to configuration in a robust format, suitable for large-scale manufacture. Given the worldwide prevalence of these parasites, the tests will have a market potential of international significance.Read moreRead less
Bacterial Proteomics: From Cell Division to Novel Antibiotic Targets. When a cell divides it is essential that each newborn cell gets a complete copy of the DNA. To ensure that this happens, cell division must be tightly controlled. It is not known how this occurs in bacteria. However, if we knew what molecules were involved in this control, we could target them to kill harmful bacteria. This project aims to identify such regulatory molecules as candidate targets for antimicrobial agents, with a ....Bacterial Proteomics: From Cell Division to Novel Antibiotic Targets. When a cell divides it is essential that each newborn cell gets a complete copy of the DNA. To ensure that this happens, cell division must be tightly controlled. It is not known how this occurs in bacteria. However, if we knew what molecules were involved in this control, we could target them to kill harmful bacteria. This project aims to identify such regulatory molecules as candidate targets for antimicrobial agents, with a view to developing powerful, novel antibiotics to protect us from the imminent threat of bioterrorism and antibiotic-resistant bacteria.
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Dynamic signaling pathways of dispersal in bacterial biofilms. This Breakthrough Science project will result in an increased understanding of the molecular processes that govern biofilm development and dispersal. While the outcomes will be directly applicable where P. aeruginosa infections continue to cause health-threatening conditions, such as in Cystic Fibrosis chronic infections, it will also be instrumental for the rational design of novel products and strategies to control biofilms of othe ....Dynamic signaling pathways of dispersal in bacterial biofilms. This Breakthrough Science project will result in an increased understanding of the molecular processes that govern biofilm development and dispersal. While the outcomes will be directly applicable where P. aeruginosa infections continue to cause health-threatening conditions, such as in Cystic Fibrosis chronic infections, it will also be instrumental for the rational design of novel products and strategies to control biofilms of other single species or of mixed species populations in many other settings. Countless environmental, industrial and clinical applications will benefit from improved antimicrobial strategies and reduced usage of antibiotics.Read moreRead less
Functional and structural diversity of the cathepsin L peptidase from the human blood fluke Schistosoma mansoni. Peptidases are enzymes that are important in many infectious and physiological disease states. For example, they are used by infectious pathogens to enter human tissues and survive inside their bodies. The same type of enzymes also contribute to tissue damage in many pathological processes in humans such as cancer, arithritis and osteoporosis. There is an urgent need to define their s ....Functional and structural diversity of the cathepsin L peptidase from the human blood fluke Schistosoma mansoni. Peptidases are enzymes that are important in many infectious and physiological disease states. For example, they are used by infectious pathogens to enter human tissues and survive inside their bodies. The same type of enzymes also contribute to tissue damage in many pathological processes in humans such as cancer, arithritis and osteoporosis. There is an urgent need to define their structure and properties so that we can employ rational approaches to develop new drugs that can combat these diseases and ailments. Read moreRead less