The multiplexed diagnosis of arbovirus infections using combinatorial probes. Viruses that cause serious diseases such as hemorrhagic fever or encephalitis must be quickly identified. Diagnostic tests based on DNA hybridisation are accurate and can be rapid but they are expensive. We will test a method for simplifying DNA tests and increasing their capabilities. DNA probes for detecting arboviruses will be designed at the ANU using new bioinformatic methods and their reliability will be model ....The multiplexed diagnosis of arbovirus infections using combinatorial probes. Viruses that cause serious diseases such as hemorrhagic fever or encephalitis must be quickly identified. Diagnostic tests based on DNA hybridisation are accurate and can be rapid but they are expensive. We will test a method for simplifying DNA tests and increasing their capabilities. DNA probes for detecting arboviruses will be designed at the ANU using new bioinformatic methods and their reliability will be modelled using all the available genetic information. Computer predictions will be experimentally tested in the PANBIO laboratory by using the probes to detect viral nucleic acids. The influence of virus genome complexity will be investigatedRead moreRead less
A high-through-put method for unlocking the mitochondrial genomes of significant pathogens. The national/community benefits of this research are: (1) to develop a long-term, high quality scientific and technological program contributing to national objectives, including the maintenance of a strong capability in basic research, the development of new scientific concepts and the enhancement of international collaborative links; (2) to strengthen the links between basic and applied research; (3) to ....A high-through-put method for unlocking the mitochondrial genomes of significant pathogens. The national/community benefits of this research are: (1) to develop a long-term, high quality scientific and technological program contributing to national objectives, including the maintenance of a strong capability in basic research, the development of new scientific concepts and the enhancement of international collaborative links; (2) to strengthen the links between basic and applied research; (3) to develop excellence in research by promoting collaborative research, resulting in a more efficient use of resources in a national and international context; (4) to enhance the skills-base in biology and biotechnology; and (5) to substantially increase global visibility through quality research, leading to an increased investment in Australian science.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
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
Origins of Parasitism in the Psocodea (Insecta). The Psocodea has 2 groups: the lice and the psocopterans (the psocids and their kin). The lice are parasites whereas the psocopterans are free-living. The Psocodea are a unique model-system that will allow us to discover the processes that preadapt arthropods for parasitism and the processes that facilitate "explosive" radiations of arthropods once they become parasites. We will infer evolutionary trees for these insects from 3 genes. Then we ....Origins of Parasitism in the Psocodea (Insecta). The Psocodea has 2 groups: the lice and the psocopterans (the psocids and their kin). The lice are parasites whereas the psocopterans are free-living. The Psocodea are a unique model-system that will allow us to discover the processes that preadapt arthropods for parasitism and the processes that facilitate "explosive" radiations of arthropods once they become parasites. We will infer evolutionary trees for these insects from 3 genes. Then we will use these trees to track the evolution of feeding, attachment, senses and reproduction through evolutionary time. Our work should provide unprecedented insight into the evolution of parasitism in the arthropods.Read 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 Evolution and Diversification of Apicomplexan Cell Invasion Mechanisms. Insights gained through this project, about the mechanisms of cell invasion in Apicomplexan parasites, will have far reaching implications for a number of parasites of great significance to humans and animals. Since host cell invasion is a key step in the parasite lifecycle, proteins identified here will be prime targets for novel drugs that prevent invasion or antigens that can be used as vaccines. This will be importan ....The Evolution and Diversification of Apicomplexan Cell Invasion Mechanisms. Insights gained through this project, about the mechanisms of cell invasion in Apicomplexan parasites, will have far reaching implications for a number of parasites of great significance to humans and animals. Since host cell invasion is a key step in the parasite lifecycle, proteins identified here will be prime targets for novel drugs that prevent invasion or antigens that can be used as vaccines. This will be important for developing new control strategies for diseases of global significance such as malaria or toxoplasmosis, as well as those of national importance to the food industry of Australia, including diseases like babesiosis and coccidiosis that cause significant economic loss to the livestock and poultry industries each year.Read moreRead less