Mapping cell wall and surface structures of Gram-positive cocci. The synthesis of the Gram-positive cell wall and protein transport are fundamental processes, the improved understanding of which will impact across a range of fields including microbiology, biochemistry and biotechnology, and the application and manipulation of Gram-positive bacteria in agriculture, industry and human health. In the long-term, the analysis of the Gram-positive ExPortal and cell wall will identify proteins that ma ....Mapping cell wall and surface structures of Gram-positive cocci. The synthesis of the Gram-positive cell wall and protein transport are fundamental processes, the improved understanding of which will impact across a range of fields including microbiology, biochemistry and biotechnology, and the application and manipulation of Gram-positive bacteria in agriculture, industry and human health. In the long-term, the analysis of the Gram-positive ExPortal and cell wall will identify proteins that may represent targets for therapeutic intervention. Additionally a precise understanding of the mechanisms of secretion of anchorless proteins will have an important impact in the biotechnology field, as new methodologies for the secretion of recombinant proteins of industrial value is a potential outcome.Read moreRead less
Safety in numbers: Bacterial aggregation and adaptation to oxidative stress. This project is a new collaboration which links two molecular microbiologists with the complementary skills required to make new insights into the molecular processes that underpin bacterial aggregation and biofilm formation. Biofilms are of immense significance in medical, industrial and environmental settings and so the fundamental information gained from this project will have wider relevance to the field of microbio ....Safety in numbers: Bacterial aggregation and adaptation to oxidative stress. This project is a new collaboration which links two molecular microbiologists with the complementary skills required to make new insights into the molecular processes that underpin bacterial aggregation and biofilm formation. Biofilms are of immense significance in medical, industrial and environmental settings and so the fundamental information gained from this project will have wider relevance to the field of microbiology. An outcome of this proposal will be fundamental knowledge about the production of surface adhesins that will form the basis for rational treatment of disease in the future. Prevention of aggregation and biofilm formation would make bacterial populations more susceptible to conventional antibiotic treatment.Read moreRead less
Molecular mechanisms of pilin glycosylation in Neisseria: a model system for protein glycosylation in bacteria. The disease causing bacteria Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens. Cell surface structures, called pili, are known to be important in allowing the bacteria to stick to host cells. Genetic and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. Until recently ....Molecular mechanisms of pilin glycosylation in Neisseria: a model system for protein glycosylation in bacteria. The disease causing bacteria Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens. Cell surface structures, called pili, are known to be important in allowing the bacteria to stick to host cells. Genetic and structural studies have identified that the protein subunits, which make up pili, are glycosylated - modified by the addition of sugars. Until recently glycosylation of Gram-negative bacterial proteins was not thought to occur, however our recent work with these bacteria, and other groups studying Pseudomonas and Campylobacter, have shown that this process may be widespread. In our previous studies, we have identified and analysed a number of genes involved in pili glycosylation, in bacteria, which make known sugar structures. We have used this information to developed models for how the biochemistry and physiology of the glycosylation system may work. With a well-established structure and many genes already identified, glycosylation in Neisseria represents the best available model system to study this novel and important process. In the proposed study we describe experiments planned to test our models and reveal the molecular detail of this process. This study could lead to major advances in our understanding of this process and, when understood, may have future applications in biotechnology.Read moreRead less
Nuclear structure and function in the nucleated planctomycete bacterium Gemmata obscuriglobus: a third cell plan for living organisms? The project will contribute knowledge of how cells such as those of animals and plants evolved from bacterial components. Origins of cell nuclei and pores in nuclear membranes will be studied via the simple eukaryote-like nucleus of the planctomycete Gemmata obscuriglobus, from Australian freshwater. Simple nuclear pore-like structures of G. obscuriglobus will he ....Nuclear structure and function in the nucleated planctomycete bacterium Gemmata obscuriglobus: a third cell plan for living organisms? The project will contribute knowledge of how cells such as those of animals and plants evolved from bacterial components. Origins of cell nuclei and pores in nuclear membranes will be studied via the simple eukaryote-like nucleus of the planctomycete Gemmata obscuriglobus, from Australian freshwater. Simple nuclear pore-like structures of G. obscuriglobus will help understanding nucleus function in animal cells, and such pores will give insight into 'minimal' composition needed for cell nuclei, and allow design of biological nanopores. The origin of the nucleus is a major problem in biology, and an Australian contribution to its solution will achieve international recognition. Read moreRead less
A Genomic Dissection of Natural Adaptation in Mate Recognition. Adaptation is a fundamental area of evolutionary biology but we know surprisingly little about its underlying genetic basis. As a process, adaptation poses several challenges for Australian society including bacterial evolution of resistance to antibiotics, HIV resistance to antiviral medications and the evolution of pesticide resistance in agricultural pests. This study will use a model system and genomic tools to test theoretical ....A Genomic Dissection of Natural Adaptation in Mate Recognition. Adaptation is a fundamental area of evolutionary biology but we know surprisingly little about its underlying genetic basis. As a process, adaptation poses several challenges for Australian society including bacterial evolution of resistance to antibiotics, HIV resistance to antiviral medications and the evolution of pesticide resistance in agricultural pests. This study will use a model system and genomic tools to test theoretical models of the genetic basis of adaptation. This integrative approach will enhance Australia's research profile in genomics and evolutionary biology. The project will provide emerging scientists with skills in areas including genomics, molecular biology, evolutionary biology and agricultural genetics.Read moreRead less
Maximising knowledge from dense SNP (single nucleotide polymorphisms) data using multi-locus analysis. The genomics revolution has made it possible to measure thousands of DNA variants in individuals. This information can be used in many ways, including to find genes that cause variation between individuals in a population and to estimate the size of the population in the past. Our study will lead an analysis method that will extract more information out of such data. This will improve the effi ....Maximising knowledge from dense SNP (single nucleotide polymorphisms) data using multi-locus analysis. The genomics revolution has made it possible to measure thousands of DNA variants in individuals. This information can be used in many ways, including to find genes that cause variation between individuals in a population and to estimate the size of the population in the past. Our study will lead an analysis method that will extract more information out of such data. This will improve the efficiency of gene mapping methods, including applications in humans for traits related to productive ageing and a healthy start to life, will allow the estimation of genetic relatedness and genetic variation in natural populations, and will lead to more efficient selection programs in agricultural populations.Read moreRead less
Sexual selection and the accumulation of deleterious mutations. Mutation is the ultimate source of all genetic variation. Understanding the nature of mutation, its frequency, the distribution of effects, and the forces of selection that remove mutational load from populations is therefore a central concern of genetics. The accumulation of mutational load in endangered species and in human populations, where the forces of selection tend not to operate, has the potential to create serious proble ....Sexual selection and the accumulation of deleterious mutations. Mutation is the ultimate source of all genetic variation. Understanding the nature of mutation, its frequency, the distribution of effects, and the forces of selection that remove mutational load from populations is therefore a central concern of genetics. The accumulation of mutational load in endangered species and in human populations, where the forces of selection tend not to operate, has the potential to create serious problems. We will determine the efficacy of sexual selection in preventing deleterious mutations from accumulating in populations. This project will provide research training opportunities in quantitative genetics, an enabling discipline in Biology.Read moreRead less
Autotransporter proteins of Escherichia coli. Autoransporters are a novel class of proteins associated with bacterial virulence properties such as adhesion, invasion and biofilm formation. Despite this, limited information is available on their functional role. The aim of this project is to characterize several of the autotransporter proteins from pathogenic E. coli. The likely contribution of these proteins to infection suggests that they are potential targets for strain attenuation and vaccine ....Autotransporter proteins of Escherichia coli. Autoransporters are a novel class of proteins associated with bacterial virulence properties such as adhesion, invasion and biofilm formation. Despite this, limited information is available on their functional role. The aim of this project is to characterize several of the autotransporter proteins from pathogenic E. coli. The likely contribution of these proteins to infection suggests that they are potential targets for strain attenuation and vaccine strain construction. Many of these proteins also mediate bacterial aggregation and are therefore targets for novel drugs that inhibit this process. The project will be carried out with a high profile partner from Denmark and will provide opportunity for travel and technology development. Read moreRead less
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
MULTIVARIATE QUANTITATIVE GENETICS AND THE LEK PARADOX. This research program as the potential to change the way evolutionary biologists view how selection changes the available patterns of genetic variance and covariance. In particular, it will highlight the possibility that a lack of genetic variance in multi-trait systems may be an important mechanism that limits the response to selection. It is therefore addresses a fundamental problem in quantitative genetics that underlies selection li ....MULTIVARIATE QUANTITATIVE GENETICS AND THE LEK PARADOX. This research program as the potential to change the way evolutionary biologists view how selection changes the available patterns of genetic variance and covariance. In particular, it will highlight the possibility that a lack of genetic variance in multi-trait systems may be an important mechanism that limits the response to selection. It is therefore addresses a fundamental problem in quantitative genetics that underlies selection limits in evolution and agriculture.Read moreRead less