A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a ....A genetic analysis of the role of an atypical hexokinase in gene regulation. This project addresses a question which is relevant to all living things-how do changes in the environment of a cell bring about a change in gene expression? The aim of this project is to investigate the role of hexokinases in gene regulation by studying the Aspergillus nidulans xprF gene, which encodes an an unusual hexokinase. Hexokinases are thought to be the glucose sensors in plants, animals and fungi, and play a role in the development of diabetes in humans. In plants, sugars affect many processes including growth, flowering, photosynthesis, nitrogen metabolism, starch synthesis, pigmentation and response to pathogens.Read moreRead less
Plasmid maintenance and interactions with the host cell and its genome. Plasmids are extrachromosomal genetic elements that play a central role in the evolution of bacteria. They are the most dynamic component of the bacterial genome, augmenting the host chromosome by conferring a range of significant phenotypes that facilitate environmental adaptation. This project aims to elucidate fundamental aspects of the relationship between plasmids and their bacterial hosts. Significant outcomes include ....Plasmid maintenance and interactions with the host cell and its genome. Plasmids are extrachromosomal genetic elements that play a central role in the evolution of bacteria. They are the most dynamic component of the bacterial genome, augmenting the host chromosome by conferring a range of significant phenotypes that facilitate environmental adaptation. This project aims to elucidate fundamental aspects of the relationship between plasmids and their bacterial hosts. Significant outcomes include understanding the molecular basis of efficient plasmid inheritance in bacterial populations, and exploration of the innovative hypothesis that plasmids modulate expression of the host chromosome, a possibility that would profoundly alter our view of how plasmids influence host phenotype.Read moreRead less
Further Genetic and Molecular studies of an Important Prokaryotic Regulator Protein TyrR. Genomes encode many functions whose expression varies dramatically depending on particular cellular environments. Special proteins called Regulator Proteins act as sensors to detect subtle changes in the environment and, in response, to influence the expression of certain genes either dampening them down or stimulating their activity. We are working with the TyrR regulator protein of the simple bacterium E ....Further Genetic and Molecular studies of an Important Prokaryotic Regulator Protein TyrR. Genomes encode many functions whose expression varies dramatically depending on particular cellular environments. Special proteins called Regulator Proteins act as sensors to detect subtle changes in the environment and, in response, to influence the expression of certain genes either dampening them down or stimulating their activity. We are working with the TyrR regulator protein of the simple bacterium Escherichia coli to elucidate the molecular strategies used in these controls. Because this protein controls the expression of a number of genes with diverse functions, evolution has selected equally diverse mechanisms to achieve appropriate transcriptional responses. The detailed knowledge of the E.coli genome and of the various genes regulated by TyrR make it an excellent system for such fundamental studies.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
Defining New Building Blocks for the Construction of Artificial Genetic Circuits. By characterising the components of a natural genetic switch, we will make available a set of well defined genetic building blocks for construction of rationally designed biological circuits. The ability to build such circuits would have significant economic benefit in areas such as metabolic engineering, to improve the efficiency of production of natural compounds from micro-organisms, and in biomedicine, for the ....Defining New Building Blocks for the Construction of Artificial Genetic Circuits. By characterising the components of a natural genetic switch, we will make available a set of well defined genetic building blocks for construction of rationally designed biological circuits. The ability to build such circuits would have significant economic benefit in areas such as metabolic engineering, to improve the efficiency of production of natural compounds from micro-organisms, and in biomedicine, for the controlled release of therapeutic compounds. The involvement of Honours and Ph.D students in this project will expose the next generation of Australian scientists to this emerging discipline. International collaboration leading to publications in high impact scientific journals will enhance Australia's scientific reputation.Read moreRead less
The evolution of bacterial pathogenesis: a genomic approach. The outcome of this research will be a better understanding of the genes involved with adaptation to particular pathogenic lifestyles. Specifically, genes that are rapidly evolving in selected bacterial pathogens of medical and veterinary importance will be identified using a bioinformatics approach that exploits the existence of multiple closely-related genome sequences. Such genes encode potential new targets for therapeutic interv ....The evolution of bacterial pathogenesis: a genomic approach. The outcome of this research will be a better understanding of the genes involved with adaptation to particular pathogenic lifestyles. Specifically, genes that are rapidly evolving in selected bacterial pathogens of medical and veterinary importance will be identified using a bioinformatics approach that exploits the existence of multiple closely-related genome sequences. Such genes encode potential new targets for therapeutic intervention that provide alternatives in the face of emerging antibiotic resistance. Importantly, the methodology developed in this project is broadly applicable to the study of evolution of bacterial pathogenesis in any background: medical, agricultural or horticultural.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
Molecular genetic analysis of genes controlling morphogenesis: Dimorphic switching in the fungus Penicillium marneffei. Fungi exist in two predominant growth forms; unicellular yeast and multicellular mould (filamentous hyphae). Some fungi can alternate between these two forms in response to environmental stimuli, a process known as dimorphic switching. The cells of these two forms have distinctive shapes and physiological capacities established by genome-wide expression patterns that are trigge ....Molecular genetic analysis of genes controlling morphogenesis: Dimorphic switching in the fungus Penicillium marneffei. Fungi exist in two predominant growth forms; unicellular yeast and multicellular mould (filamentous hyphae). Some fungi can alternate between these two forms in response to environmental stimuli, a process known as dimorphic switching. The cells of these two forms have distinctive shapes and physiological capacities established by genome-wide expression patterns that are triggered by signalling pathways. This research aims to understand the fundamental mechanisms controlling dimorphic switching using Penicillium marneffei, a model system. P. marneffei switches between yeast and filamentous forms in response to temperature. Uncovering the molecular mechanisms that control dimorphic switching has important implications for biotechnology and medicine.Read moreRead less
Regulation of nuclear localisation of the AreA transcription factor in Aspergillus nidulans. An understanding of the means by which the expression of genes is regulated is of fundamental significance. Changes in gene expression are central to the development, growth and viability of all cells and their response to environmental changes/stresses. This study uses the fungus Aspergillus nidulans as an excellent molecular genetic tool to investigate how a key regulatory protein controls gene expres ....Regulation of nuclear localisation of the AreA transcription factor in Aspergillus nidulans. An understanding of the means by which the expression of genes is regulated is of fundamental significance. Changes in gene expression are central to the development, growth and viability of all cells and their response to environmental changes/stresses. This study uses the fungus Aspergillus nidulans as an excellent molecular genetic tool to investigate how a key regulatory protein controls gene expression in response to nitrogen starvation stress. Our understanding of these dynamic processes informs our approaches to the development of cancer therapies, to commercial biotechnology application and to control of human, plant and animal pathogens in which the infectious process is triggered by environmental stress. Read moreRead less
Decoding regulatory RNA function in bacteria. All complex biological processes in bacterial cells appear to utilise regulatory small RNAs to control gene expression, but we lack a systems-level understanding of their functions and mechanisms of control. This proposal aims to address this fundamental knowledge gap using machine learning and cutting-edge, systems-level techniques to determine how small RNA sequence and structure determines function. Small RNAs have been found to control a broad ra ....Decoding regulatory RNA function in bacteria. All complex biological processes in bacterial cells appear to utilise regulatory small RNAs to control gene expression, but we lack a systems-level understanding of their functions and mechanisms of control. This proposal aims to address this fundamental knowledge gap using machine learning and cutting-edge, systems-level techniques to determine how small RNA sequence and structure determines function. Small RNAs have been found to control a broad range of traits including metabolism, biofilm formation, antibiotic tolerance, and virulence. The work proposed here will enhance our ability to predict and control bacterial gene expression with potential future impacts on bioproduction, synthetic biology, and veterinary and medical microbiology.Read moreRead less