Autotransporter proteins of enterohemorrhagic Escherichia coli O157:H7. Escherichi (E.) coli O157:H7 has caused hundreds of outbreaks in the United States and United Kingdom. Although not currently a major problem in Australia, the emergence of E. coli O157:H7 here would have serious implications for our meat and livestock industry. This study will provide important information for the selection of vaccine antigens used to prevent the colonisation of cattle with E. coli O157:H7 and other diarrho ....Autotransporter proteins of enterohemorrhagic Escherichia coli O157:H7. Escherichi (E.) coli O157:H7 has caused hundreds of outbreaks in the United States and United Kingdom. Although not currently a major problem in Australia, the emergence of E. coli O157:H7 here would have serious implications for our meat and livestock industry. This study will provide important information for the selection of vaccine antigens used to prevent the colonisation of cattle with E. coli O157:H7 and other diarrhoeagenic E. coli serotypes. A direct outcome of this will be improved human health, as E. coli O157:H7 can cause life threatening infections in humans. The study will also examine the contribution of specific adhesins to biofilm formation; measures to prevent biofilm formation may reduce the persistence and spread of E. coli O157:H7 in the environment.Read moreRead less
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
The role of virulence factors of Clostridium difficile in food animals. Disease caused by the bacterium Clostridium difficile are a significant food production animal and public health problem in many countries. Specific animal and human public health resources have been allocated in many countries in efforts to mitigate the growing epidemics. The study proposed in this application presents a significant opportunity to learn about the virulence factors of animal strains of this bacterium about w ....The role of virulence factors of Clostridium difficile in food animals. Disease caused by the bacterium Clostridium difficile are a significant food production animal and public health problem in many countries. Specific animal and human public health resources have been allocated in many countries in efforts to mitigate the growing epidemics. The study proposed in this application presents a significant opportunity to learn about the virulence factors of animal strains of this bacterium about which very little is known. This project will lead to rationally designed preventative and treatment strategies that apply to both animals and humans, thereby impeding epidemics caused by C. difficile in Australia.Read moreRead less
Identification of the basic elements of Plasmodium transcription. This Discovery Project falls under the NRP for safeguarding Australia. Australian troops stationed in malaria endemic areas face the threat of infection and require medical attention upon return.Any research on malaria will expand our knowledge on prevention and treatment. Australia near malariaendemic locations such as Indonesia and Papua New Guinea.These countries do not have the means to support effective basic research into ....Identification of the basic elements of Plasmodium transcription. This Discovery Project falls under the NRP for safeguarding Australia. Australian troops stationed in malaria endemic areas face the threat of infection and require medical attention upon return.Any research on malaria will expand our knowledge on prevention and treatment. Australia near malariaendemic locations such as Indonesia and Papua New Guinea.These countries do not have the means to support effective basic research into the disease and wealthier countries such as Australia have the responsibility to fill this void.Furthermore, the aims of this Discovery Project are unique within the Australian malaria research community and the results fully complement other studies on transcription regulation of antigenic genes. 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
Discovery of Novel Respiratory Viruses Causing Influenza-Like Illness in Healthy Australian Adults Aged 18 to 64 Years. This work will inform our understanding of the causes of acute respiratory illnesses in Australia at the present time by looking for both known and previously undiscovered respiratory viruses. Increasing the knowledge base regarding causes of disease will have downstream relevance for health policy planners seeking to assess the burden of disease due to different causes. Early ....Discovery of Novel Respiratory Viruses Causing Influenza-Like Illness in Healthy Australian Adults Aged 18 to 64 Years. This work will inform our understanding of the causes of acute respiratory illnesses in Australia at the present time by looking for both known and previously undiscovered respiratory viruses. Increasing the knowledge base regarding causes of disease will have downstream relevance for health policy planners seeking to assess the burden of disease due to different causes. Early identification and description of new diseases will allow pre-emptive evaluation of new public health threats. This information will help to ensure availability and marketability of vaccines to prevent infection.Read moreRead less
A fundamental study of the role of signal transduction pathways in the regulation of Chlamydia's complex developmental cycle. Chlamydia are unique organisms in the microbial world. They are among the smallest bacteria and yet have a complex two-stage developmental cycle. In addition they are major causes of disease in animals and humans with no vaccines available. We have used the recent flood of full genome sequence data to identify over 30 new cell signalling proteins. By understanding how the ....A fundamental study of the role of signal transduction pathways in the regulation of Chlamydia's complex developmental cycle. Chlamydia are unique organisms in the microbial world. They are among the smallest bacteria and yet have a complex two-stage developmental cycle. In addition they are major causes of disease in animals and humans with no vaccines available. We have used the recent flood of full genome sequence data to identify over 30 new cell signalling proteins. By understanding how these cell signaling proteins are organized into pathways and how this microorganism controls its complex growth and developmental cycle, we will be able to develop novel methods of control. We are at the fore front of international research and therefore uniquely placed to conduct this project.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