Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100089
Funder
Australian Research Council
Funding Amount
$700,000.00
Summary
Super-resolution fluorescence microscopy. The prestigious journal Nature Methods named super-resolution fluorescent microscopy as the Method of the Year 2008. This recognition is justified because fluorescent imaging on the molecular scale will revolutionise biological sciences. It will literally change the way we see the smallest building blocks of life and this allows researchers to identify the function of proteins and lipids in health and disease. This breakthrough technology is currently no ....Super-resolution fluorescence microscopy. The prestigious journal Nature Methods named super-resolution fluorescent microscopy as the Method of the Year 2008. This recognition is justified because fluorescent imaging on the molecular scale will revolutionise biological sciences. It will literally change the way we see the smallest building blocks of life and this allows researchers to identify the function of proteins and lipids in health and disease. This breakthrough technology is currently not available to researchers in Australia. Super-resolution fluorescence microscopy would extend Australia's leading position in the fundamental biological sciences, bio- and nano-technologies as well as imaging and microscopy.Read moreRead less
Lipid raft and cyotoskeleton organization: How membrane domains give cells direction. For a large number of cells in our body it is imperative that they are able to orientate themselves relative to their environment, sense direction and translate incoming signals. To do so it is hypothesised that lipids on the cell surface are redistributed to form specialized domains. An asymmetric distribution of membrane domains can provide cells with a front and rear end and can further concentrate and co-or ....Lipid raft and cyotoskeleton organization: How membrane domains give cells direction. For a large number of cells in our body it is imperative that they are able to orientate themselves relative to their environment, sense direction and translate incoming signals. To do so it is hypothesised that lipids on the cell surface are redistributed to form specialized domains. An asymmetric distribution of membrane domains can provide cells with a front and rear end and can further concentrate and co-ordinate signalling molecules to a specific site. The project will determine the role of lipid domain in stabilizing cell shape and their remodelling during cell migration, the digestion of foreign particles and the formation of cell-cell contacts.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
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
Genetic modification and lyophilisation of microorganisms for the generation of bacteriological internal quality controls. The development of internal quality control micro-organisms in precise numbers is necessary for the evolution of standard methodology in microbiology, which until now, remains obsolete, because it relies on inaccurate methods to produce quantitative and qualitative results. The research described here is largely based on molecular techniques to genetically tag micro-organism ....Genetic modification and lyophilisation of microorganisms for the generation of bacteriological internal quality controls. The development of internal quality control micro-organisms in precise numbers is necessary for the evolution of standard methodology in microbiology, which until now, remains obsolete, because it relies on inaccurate methods to produce quantitative and qualitative results. The research described here is largely based on molecular techniques to genetically tag micro-organisms with fluorescent proteins and pigment producing enzymes, and on the manipulation of growth and storage conditions to maximize the survival of micro-organisms during lyophilisation. Successful completion and application of the proposed project through existing patents owned by BTF, will revolutionise the way microbiological tests are performed worldwide.Read moreRead less
Role of the proteasome in eradication of misfolded proteins in fungal cell factories. Filamentous fungi contribute to the well being of modern society as surrogate hosts for the synthesis of vaccines, hormones and enzymes for their application to health, agriculture, industry and the environment. However, attempts to express foreign proteins to the full potential of a given system have been disappointing. It is vital to understand unexplored molecular and physiological factors such as protein ....Role of the proteasome in eradication of misfolded proteins in fungal cell factories. Filamentous fungi contribute to the well being of modern society as surrogate hosts for the synthesis of vaccines, hormones and enzymes for their application to health, agriculture, industry and the environment. However, attempts to express foreign proteins to the full potential of a given system have been disappointing. It is vital to understand unexplored molecular and physiological factors such as protein quality control in the cell to take advantage of the global opportunities that recombinant gene expression indisputably offers in the form of unrestricted supply of proteins of social and economic value. The project will create novel IP and licensing opportunities for Australia.Read moreRead less
Bacterial innovation and evolution: Molecular prospecting by targeting integrons and gene cassettes. Bacteria can respond rapidly to environmental change by acquiring new genes via lateral gene transfer. A DNA element called the integron can capture, mobilise and express genes, thereby playing a role in the transfer process. We have discovered that integrons are surprisingly abundant in the environment and are associated with a hitherto unsuspected diversity of novel genes. In this study we will ....Bacterial innovation and evolution: Molecular prospecting by targeting integrons and gene cassettes. Bacteria can respond rapidly to environmental change by acquiring new genes via lateral gene transfer. A DNA element called the integron can capture, mobilise and express genes, thereby playing a role in the transfer process. We have discovered that integrons are surprisingly abundant in the environment and are associated with a hitherto unsuspected diversity of novel genes. In this study we will assess the diversity of environmental integrons and examine their contribution to bacterial evolution. Further, we aim to use integron systems to prospect for novel genes and contract new enzyme pathways by directed evolution.
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Biosynthesis of nonribosomal peptide toxins in cyanobacteria: A functional characterisation of microcystin synthetase. Microcystins are potent toxins and tumour promoters produced by cyanobacteria associated with blue-green algal blooms. This non-ribosomal peptide is produced by microcystin synthetase, a unique enzyme complex comprised of peptide synthetases, polyketide synthases, and integrated accessory enzymes. We have identified and characterised the extensive gene cluster encoding this enzy ....Biosynthesis of nonribosomal peptide toxins in cyanobacteria: A functional characterisation of microcystin synthetase. Microcystins are potent toxins and tumour promoters produced by cyanobacteria associated with blue-green algal blooms. This non-ribosomal peptide is produced by microcystin synthetase, a unique enzyme complex comprised of peptide synthetases, polyketide synthases, and integrated accessory enzymes. We have identified and characterised the extensive gene cluster encoding this enzyme. This project describes the biochemical characterisation of specific enzyme activities within microcystin synthetase and how they determine the final structure and toxicity of the many forms of microcystin. Interactions between this enzyme complex and its substrate amino acids will provide information for the genetic engineering of this and similar natural products.Read moreRead less
Recovery and characterization of monooxygenases for biocatalysis and bioremediation through development of novel DNA- and protein-based technology. Australia contains hundreds of sites contaminated with toxic waste and judged to pose significant risk of harm to the public. This project will identify enzymes and organisms capable of remediating such contaminated sites by natural processes. It will also result in training of persons and development of techniques that will contribute to making bi ....Recovery and characterization of monooxygenases for biocatalysis and bioremediation through development of novel DNA- and protein-based technology. Australia contains hundreds of sites contaminated with toxic waste and judged to pose significant risk of harm to the public. This project will identify enzymes and organisms capable of remediating such contaminated sites by natural processes. It will also result in training of persons and development of techniques that will contribute to making bioremediation an environmentally sustainable and cost-effective technology. The environmental proteomics strategy is a frontier technology, expected to have broad applications in health, food science and the environment. Our development of this technology will create a wide range of opportunities for Australian scientists and companies.Read moreRead less