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 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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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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Genomic and molecular characterisation of a novel Australian leishmania pathogen. Leishmaniasis is the second most serious protozoal disease after malaria. This project will help characterise the first Leishmania species identified in Australia providing molecular tools to monitor the pathogen and a detailed assessment of any potential risk to human health. Comparative analysis with more pathogenic species will help identify genes and mechanisms that determine the progression of human disease le ....Genomic and molecular characterisation of a novel Australian leishmania pathogen. Leishmaniasis is the second most serious protozoal disease after malaria. This project will help characterise the first Leishmania species identified in Australia providing molecular tools to monitor the pathogen and a detailed assessment of any potential risk to human health. Comparative analysis with more pathogenic species will help identify genes and mechanisms that determine the progression of human disease leading to the potential identification of new drug and vaccine targets. The methodologies and expertise developed will be used will be available to other research groups working on infectious diseases.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
Host cell targets of bacterial virulence effectors. The research described in this proposal will result in a better understanding of the cell biology of host-pathogen interactions. We are in a unique position to analyze the importance of protein/protein interactions between bacterial virulence determinants and host cell proteins using a range of cell biology techniques to address the fundamental, molecular basis of the host-pathogen interaction. In addition we will construct a new genetic tool ....Host cell targets of bacterial virulence effectors. The research described in this proposal will result in a better understanding of the cell biology of host-pathogen interactions. We are in a unique position to analyze the importance of protein/protein interactions between bacterial virulence determinants and host cell proteins using a range of cell biology techniques to address the fundamental, molecular basis of the host-pathogen interaction. In addition we will construct a new genetic tool to identify novel bacterial virulence determinants. We anticipate that a greater knowledge of the factors that contribute to the host-pathogen interaction will provide new insights into the subversion of host cell processes by bacterial pathogens of animals, plants and humans.
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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
Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identifie ....Phasevarions of Haemophilus influenzae: mechanisms and origins of a novel epigenetic system controlling coordinated random switching in expression of multiple genes. Central to the utilisation of biological information is our ability to identify and interpret DNA sequence information from genomes. In bacteria that cause disease, these investigations can identify key aspects of the infectious process or potential components of vaccines or new targets for antibiotics. Our recent work has identified a new genetic system, the 'phasevarion', that mediates random expression of multiple genes. The proposed research aims to advance our understanding of gene expression at the most basic level, revealing how bacteria generate diverse populations to evade environmental and immune stresses, and facilitating improved interpretation and use of DNA sequences for researchers and industry in this field.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
Next generation metagenomics. Applying the latest scientific advances supports society directly through promoting a knowledge based economy, as well as indirectly through securing agricultural productivity, improved biomedical applications and a greater understanding of our changing environment. Establishing these methods places Australia at the forefront of genomics technology with direct applications for Australian biomedical and biotechnology industries. Applying next generation sequencing fo ....Next generation metagenomics. Applying the latest scientific advances supports society directly through promoting a knowledge based economy, as well as indirectly through securing agricultural productivity, improved biomedical applications and a greater understanding of our changing environment. Establishing these methods places Australia at the forefront of genomics technology with direct applications for Australian biomedical and biotechnology industries. Applying next generation sequencing for metagenomics will provide a detailed understanding of microbial population structures and lead to advances in biomedicine, agriculture and environmental science. Read moreRead less