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
Metabolic control of gene expression networks and microbiome interactions. The proposal aims to advance our understanding of how metabolism (and resulting metabolites) regulate the expression of genes, and investigate how these processes dictate the interaction of microbiota with the immune system. The project is expected to generate transformative knowledge of gene regulation, a fundamental process for cellular function, and decipher how the microbiome yeast Candida albicans interacts with immu ....Metabolic control of gene expression networks and microbiome interactions. The proposal aims to advance our understanding of how metabolism (and resulting metabolites) regulate the expression of genes, and investigate how these processes dictate the interaction of microbiota with the immune system. The project is expected to generate transformative knowledge of gene regulation, a fundamental process for cellular function, and decipher how the microbiome yeast Candida albicans interacts with immune cells and bacteria. By utilising a powerful combination of molecular and systems biology with molecular genetics and imaging, the project outcomes should foster interdisciplinary collaborations and build capacity for fundamental and applied research to benefit academia and industry, locally and globally.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE140101728
Funder
Australian Research Council
Funding Amount
$395,220.00
Summary
The regulation and evolution of posttranscriptional gene networks. The ability of cells to regulate gene expression is key for organism development, adaptation to new environments and evolutionary changes that shape the diversity of life on Earth. This project studies the RNA binding proteins called PUFs which are central for gene expression in diverse organisms. Using cutting-edge new generation systems biology approaches, this project will study how PUF proteins regulate genes to enable metabo ....The regulation and evolution of posttranscriptional gene networks. The ability of cells to regulate gene expression is key for organism development, adaptation to new environments and evolutionary changes that shape the diversity of life on Earth. This project studies the RNA binding proteins called PUFs which are central for gene expression in diverse organisms. Using cutting-edge new generation systems biology approaches, this project will study how PUF proteins regulate genes to enable metabolic adaptation, differentiation of cell types and the evolution of new gene expression outputs in distinct biological species. The outcomes will include new insights into the regulation and evolution of posttranscriptional gene networks. Read moreRead less
Discovery of bioactive natural substances from uncultured bacteria and their production using photosynthetic reactor technology. The range and rate of natural product discovery is the limiting factor in developing new therapies for cancer and infectious disease. This research will enable the discovery of new drugs, coupled to their production in a photosynthetic expression system. This represents a truly “green” and sustainable technology for the pharmaceutical industry.
How do Microbes Grow in High Salt at Very Cold Temperatures. The proposed research aims to define mechanisms of survival and speciation that underpin the capacity of a novel group of Antarctic microorganisms to evolve dominance in their very cold (-20 degrees Celsius) and very salty environment. Most (~85 per cent) of the Earth's biosphere is cold (<5 degrees Celsius), and yet contains a rich diversity of microorganisms of which we know little. The uniqueness and sensitivity of Antarctica partic ....How do Microbes Grow in High Salt at Very Cold Temperatures. The proposed research aims to define mechanisms of survival and speciation that underpin the capacity of a novel group of Antarctic microorganisms to evolve dominance in their very cold (-20 degrees Celsius) and very salty environment. Most (~85 per cent) of the Earth's biosphere is cold (<5 degrees Celsius), and yet contains a rich diversity of microorganisms of which we know little. The uniqueness and sensitivity of Antarctica particularly demands that we rapidly improve our understanding of its biology. The discoveries made could provide fundamental insight about speciation - processes controlling which life forms that colonise the planet.Read moreRead less
Genetic regulation of developmental competence: molecular mechanisms that establish a competent state. Development is a key biological process for multicellular life. This project will study development using a simple, established experimental organism, a fungus, as a model for development in other organisms, including humans. Moreover, fungi directly impact on life at many levels and understanding their biology has direct benefits for society.
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