Environmental influence on evolutionary processes in bacterial populations. Bacterial populations exhibit remarkable adaptive capabilities in many environmental and medical settings. They respond to environmental stress in terms of altered gene expression, but what are the effects on mutation rates and fitness when cells grow at suboptimal growth rates? We plan to test whether the physiological state of an ancestral population is a determinant of a population's subsequent response to selection. ....Environmental influence on evolutionary processes in bacterial populations. Bacterial populations exhibit remarkable adaptive capabilities in many environmental and medical settings. They respond to environmental stress in terms of altered gene expression, but what are the effects on mutation rates and fitness when cells grow at suboptimal growth rates? We plan to test whether the physiological state of an ancestral population is a determinant of a population's subsequent response to selection. A simple model system using controlled culture conditions will be used to investigate the linkage between environment, mutation rate and fitness under selection. Demonstration of these linkages will have significant impacts on microbiology and understanding evolution.Read moreRead less
Genetics and evolution of Shigella O antigens. We use genome scale sequencing techniques to sequence 26 O-antigen gene clusters from Shigella. With the seven already known, this will give sequences for every O-antigen of Shigella. This will be the first time that such set is fully sequenced. Shigella are human specific pathogens, have emerged with the evolution of humans. O-antigens are important for their life and pathogenicity. This project will greatly extend our knowledge of the genetic basi ....Genetics and evolution of Shigella O antigens. We use genome scale sequencing techniques to sequence 26 O-antigen gene clusters from Shigella. With the seven already known, this will give sequences for every O-antigen of Shigella. This will be the first time that such set is fully sequenced. Shigella are human specific pathogens, have emerged with the evolution of humans. O-antigens are important for their life and pathogenicity. This project will greatly extend our knowledge of the genetic basis and evolution of this important polymorphism. O-antigens are used for typing Shigella and also elicit strong immunity. The molecular data will help establish DNA based typing and vaccine development.Read moreRead less
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
Development of SELEX technology (Systematic Evolution of Ligands by EXponential enrichment). A recently developed in vitro genetic selection technique has allowed the isolation of oligonucleotides that can bind target molecules with high affinity and specificity. The strategy know as SELEX (Systematic Evolution of Ligands by EXponential enrichment) uses protein biochemistry and PCR technology, with subsequent repeated rounds of selection and amplification, to screen vast libraries of oligonucle ....Development of SELEX technology (Systematic Evolution of Ligands by EXponential enrichment). A recently developed in vitro genetic selection technique has allowed the isolation of oligonucleotides that can bind target molecules with high affinity and specificity. The strategy know as SELEX (Systematic Evolution of Ligands by EXponential enrichment) uses protein biochemistry and PCR technology, with subsequent repeated rounds of selection and amplification, to screen vast libraries of oligonucleotides (RNA or DNA) for their ability to bind target proteins. This procedure will be developed by UNSW in collaboration with the biotech company BTF Plc., Ltd., to be used in two applications. The first is the research interest of UNSW and involves the development of aptamers against hepatitis C virus. The second lies within the interests of BTF and will involve the development of aptamers against the water borne pathogen Cryptosporidium parvum.Read moreRead less
Variation in bacterial genomic mutation rates. Our measurement of global mutation rates will contribute to an understanding of the evolutionary properties of bacteria, the most diverse and successful organisms in the biosphere. Bacterial variation and culture richness contributes not only to ecological processes but also to emerging diseases. The studies will enhance capabilities essential in interpreting the evolution of epidemics and the kinetics of bacterial sweeps in nature. Variation also p ....Variation in bacterial genomic mutation rates. Our measurement of global mutation rates will contribute to an understanding of the evolutionary properties of bacteria, the most diverse and successful organisms in the biosphere. Bacterial variation and culture richness contributes not only to ecological processes but also to emerging diseases. The studies will enhance capabilities essential in interpreting the evolution of epidemics and the kinetics of bacterial sweeps in nature. Variation also provides the source material for exploitation of bacterial products such as antibiotics. The results from understanding a complete set of mutational changes through genomic analysis will provide the most direct estimates of variation in evolving bacteria.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
Development of an anti-Chlamydia vaccine for the koala. The koala is one of Australia's main icons and a major drawcard for tourists. However, it suffers from debilitating disease due to the bacterium Chlamydia, which can lead to severe conjunctivitis, eventual blindness in both sexes, and the females develop untreatable cysts and can become infertile. This project will develop a Chlamydia vaccine to be administered to healthy and diseased koalas in zoos, sanctuaries, koala care centres, relocat ....Development of an anti-Chlamydia vaccine for the koala. The koala is one of Australia's main icons and a major drawcard for tourists. However, it suffers from debilitating disease due to the bacterium Chlamydia, which can lead to severe conjunctivitis, eventual blindness in both sexes, and the females develop untreatable cysts and can become infertile. This project will develop a Chlamydia vaccine to be administered to healthy and diseased koalas in zoos, sanctuaries, koala care centres, relocation programs and eventually perhaps even wild populations. The vaccine findings may also be transferable to other animals and may also even assist the development of a human Chlamydia vaccine.Read moreRead less
Microfluidic device for microbial separation and concentration. This project will enhance Australia's capabilities and presence in the rapidly expanding field of chemical and biological analysis systems on a chip. We will develop and build handheld devices for microbial concentration that will facilitate earlier and easier detection of potentially pathogenic organisms in critical situations such as epidemiological crises or forensics. The portability and ease of operation of our integrated micro ....Microfluidic device for microbial separation and concentration. This project will enhance Australia's capabilities and presence in the rapidly expanding field of chemical and biological analysis systems on a chip. We will develop and build handheld devices for microbial concentration that will facilitate earlier and easier detection of potentially pathogenic organisms in critical situations such as epidemiological crises or forensics. The portability and ease of operation of our integrated microfluidic devices and their increased resilience to blockages make them ideal for use in remote areas and non-laboratory settings. Application areas will include disease detection, microbial contamination in food industries and water quality monitoring.Read moreRead less
Molecular and antibody analysis of cytomegalovirus (CMV) infection of fetal and placental cells. CMV is a beta herpesvirus with many unknown molecular mechanisms associated with cellular infection. The virus infects placental cells in vivo, although pathogenesis of viral damage to these cells has been extremely difficult to study in vitro. We have commenced a study to i) demonstrate the molecular accompaniments of infection of placental cells in vitro, ii) determine the genotypic characteristics ....Molecular and antibody analysis of cytomegalovirus (CMV) infection of fetal and placental cells. CMV is a beta herpesvirus with many unknown molecular mechanisms associated with cellular infection. The virus infects placental cells in vivo, although pathogenesis of viral damage to these cells has been extremely difficult to study in vitro. We have commenced a study to i) demonstrate the molecular accompaniments of infection of placental cells in vitro, ii) determine the genotypic characteristics of congenital CMV infections, in collaboration with Abbott Diagnostics, and iii) produce an in vivo model of CMV infection to demonstrate the pathogenesis of cellular injury. The combination of molecular expertise at UNSW with monoclonal antibody expertise from Abbott Diagnostics mean this project is unique worldwide.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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