Biohumanities: Philosophical, Historical, and Socio-Cultural Studies of Contemporary Bioscience. Improving understanding of the meaning and implications of contemporary bioscience, especially genetics and molecular biology, through bioliterate research in the humanities and social sciences, and conversely through better assimilation of bioscience and its significance by the humanities and social sciences. The research will be conducted in close collaboration with the Australian scientific commun ....Biohumanities: Philosophical, Historical, and Socio-Cultural Studies of Contemporary Bioscience. Improving understanding of the meaning and implications of contemporary bioscience, especially genetics and molecular biology, through bioliterate research in the humanities and social sciences, and conversely through better assimilation of bioscience and its significance by the humanities and social sciences. The research will be conducted in close collaboration with the Australian scientific community and will be disseminated back to the scientific community, to the humanities and to the Australian public. The project will bring to Australia the strengths of the applicant's existing collaborations with leading research centres in this field in the USA, UK and Canada.Read moreRead less
A genomic approach to the mechanism of meiotic recombination in Neurospora. Recombination shuffles DNA sequences between homologous chromosomes during the reduction division in the life cycle of higher organisms. Along with mutation, it is a key process in evolution. Understanding of the molecular processes involved in recombination is largely based on yeast, which is intolerant of significant levels of sequence mismatch, limiting the resolution of analyses of normal recombination events. We hav ....A genomic approach to the mechanism of meiotic recombination in Neurospora. Recombination shuffles DNA sequences between homologous chromosomes during the reduction division in the life cycle of higher organisms. Along with mutation, it is a key process in evolution. Understanding of the molecular processes involved in recombination is largely based on yeast, which is intolerant of significant levels of sequence mismatch, limiting the resolution of analyses of normal recombination events. We have shown that Neurospora, like other less tractable multicellular eukaryotes, is tolerant of sequence mismatch, allowing high resolution analysis of individual recombination events. This project will build on fundamental advances we have already made in understanding how recombination occurs.Read moreRead less
Controlling the rate of transcription and translation of Rubisco transgenes effectively in higher-plant plastids. Genetic transformation of the circular genome of the plastids provides a containable means for modifying plant growth by manipulating photosynthesis. Although the transformation mechanism is precise, predicting the level of foreign gene expression is difficult because the amounts of messenger RNA and protein produced by foreign genes in plastids varies widely, even when the protein a ....Controlling the rate of transcription and translation of Rubisco transgenes effectively in higher-plant plastids. Genetic transformation of the circular genome of the plastids provides a containable means for modifying plant growth by manipulating photosynthesis. Although the transformation mechanism is precise, predicting the level of foreign gene expression is difficult because the amounts of messenger RNA and protein produced by foreign genes in plastids varies widely, even when the protein assembles without difficulty. This project will devise strategies for controlling this variability that will facilitate attempts to exploit plastid transformation for transplanting better versions of the photosynthetic CO2-fixing enzyme, Rubisco, into plants to improve their growth efficiency in terms of water, fertiliser and light use.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
MOLECULAR BREEDING OF CYTOCHROME P450 ENZYMES. Cytochrome P450s are enzymes that catalyse an impressive array of oxidative transformations. However, there is little available data on how to modify their substrate specificity and generate tailored biocatalysts. We plan to use an emerging technology known as DNA shuffling to create libraries of P450s with varying activities. These will then be screened for enzymes that can catalyse the formation of indigo (a blue dye) and indirubin (a chemother ....MOLECULAR BREEDING OF CYTOCHROME P450 ENZYMES. Cytochrome P450s are enzymes that catalyse an impressive array of oxidative transformations. However, there is little available data on how to modify their substrate specificity and generate tailored biocatalysts. We plan to use an emerging technology known as DNA shuffling to create libraries of P450s with varying activities. These will then be screened for enzymes that can catalyse the formation of indigo (a blue dye) and indirubin (a chemotherapeutic agent). The enzymes that catalyse indigo formation will be useful in the production of coloured transgenic plants and those that produce indirubin will have a role in gene therapy.Read moreRead less
Practical strategies for engineering the CO2-fixing enzyme, Rubisco, whose subunits are encoded in different subcellular compartments. My recent replacement of the plant CO2-fixing enzyme, Rubisco, with a less efficient bacterial version, with a single type of subunit encoded by a single gene, demonstrated the feasibility of replacing Rubisco. This encourages ongoing attempts to replace plant Rubisco with more efficient versions that would allow the plants to grow with less water, fertiliser or ....Practical strategies for engineering the CO2-fixing enzyme, Rubisco, whose subunits are encoded in different subcellular compartments. My recent replacement of the plant CO2-fixing enzyme, Rubisco, with a less efficient bacterial version, with a single type of subunit encoded by a single gene, demonstrated the feasibility of replacing Rubisco. This encourages ongoing attempts to replace plant Rubisco with more efficient versions that would allow the plants to grow with less water, fertiliser or light. The most efficient Rubiscos are more complex, with two different types of subunits which, in plants, are encoded in different subcellular compartments (nucleus and plastid). This proposal addresses the challenges associated with complementary engineering both genomes to substitute foreign Rubiscos into higher-plant chloroplasts.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100008
Funder
Australian Research Council
Funding Amount
$350,000.00
Summary
Laser microdissection microscopy system for cell and development biology. The University of Newcastle has invested heavily in its biological and life sciences to create a research nexus focusing on national research priorities in biotechnology and environmental protection. The live cell laser microdissection platform will be utilised by scientists researching such strategically important areas as developmental biology, intracellular signalling cascades, cell cycle dynamics, plant development and ....Laser microdissection microscopy system for cell and development biology. The University of Newcastle has invested heavily in its biological and life sciences to create a research nexus focusing on national research priorities in biotechnology and environmental protection. The live cell laser microdissection platform will be utilised by scientists researching such strategically important areas as developmental biology, intracellular signalling cascades, cell cycle dynamics, plant development and microbiology. Moreover, this component of the University's research portfolio plays a major role in the postgraduate training of young Australian scientists who will, in turn, fuel future developments in both the life sciences and biotechnology industries.Read moreRead less
Enantioselective nitrilases from filamentous fungi. The optical characteristics (chirality) of chemical precursors are important for many fine chemicals. Chiral intermediates are in high demand by the pharmaceutical and agrochemical industries for the preparation of bulk drug intermediates and agricultural products. Nitriles are attractive starting points but their conversion to corresponding amides and carboxylic acids generates significant wastes. Their hydrolysis can be performed under mil ....Enantioselective nitrilases from filamentous fungi. The optical characteristics (chirality) of chemical precursors are important for many fine chemicals. Chiral intermediates are in high demand by the pharmaceutical and agrochemical industries for the preparation of bulk drug intermediates and agricultural products. Nitriles are attractive starting points but their conversion to corresponding amides and carboxylic acids generates significant wastes. Their hydrolysis can be performed under mild conditions by enzymes termed nitrilases. We will work on fungal nitrilases as they present a globally attractive, yet untapped commercial target. The outcome for Applimex will be a suite of biocatalysts specific for the production of key intermediates for drug and agrochemical syntheses.Read moreRead less
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
Novel coding and decoding in suspension arrays for accelerated biomolecular discovery and personalised medicine. This project will establish an advanced multiplexing technique to rapidly analyse complex biological mixtures, such as cell lysates, food samples or body fluids. It will enable the analysis of not tens, but thousands or more distinctive molecular targets in a single test. This will build the foundations for future generation bioassays, paving the way to emerging personalised medicine. ....Novel coding and decoding in suspension arrays for accelerated biomolecular discovery and personalised medicine. This project will establish an advanced multiplexing technique to rapidly analyse complex biological mixtures, such as cell lysates, food samples or body fluids. It will enable the analysis of not tens, but thousands or more distinctive molecular targets in a single test. This will build the foundations for future generation bioassays, paving the way to emerging personalised medicine. This will lead to new personal diagnostics tools for rapid genotype profiling, to better tailor therapy to the individual patient's specific characteristics. As well as the potential to improve health outcomes, the project will generate significant intellectual property and the opportunity for development of new diagnostic instrumentation in Australia.Read moreRead less