Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100010
Funder
Australian Research Council
Funding Amount
$720,000.00
Summary
A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the ....A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the nation's research priorities. It will enable: fundamental studies of cancer, neural diseases and immune disorders; the development of frontier technologies, such as smart nanomaterials, biosensors and targeted drug delivery; and applied research to help plants and soils adapt to climate variability, and to increase sustainable use of water.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
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
Enhancing plant photosynthesis by engineering the carbon dioxide (CO2)-fixing enzyme Rubisco. Improving the ability of crops to use water, sunlight and fertiliser more efficiently would have economic benefits for Australia and ease the environmental impacts associated with agricultural practices. Photosynthesis research has confirmed that such improvements are theoretically possible by enhancing the efficiency of the protein, Rubisco, which initiates the conversion of carbon dioxide into carbon ....Enhancing plant photosynthesis by engineering the carbon dioxide (CO2)-fixing enzyme Rubisco. Improving the ability of crops to use water, sunlight and fertiliser more efficiently would have economic benefits for Australia and ease the environmental impacts associated with agricultural practices. Photosynthesis research has confirmed that such improvements are theoretically possible by enhancing the efficiency of the protein, Rubisco, which initiates the conversion of carbon dioxide into carbon compounds required for growth. The biotechnological research proposed here uses unique capabilities to improve our understanding of structural features in Rubisco that influence its assembly and functional efficiency in plants. This knowledge will pave the way for transplanting more efficient Rubisco into crops to improve their growth.Read moreRead less
BIOCATALYSTS MINED FROM CYTOCHROME P450 LIBRARIES: AN INNOVATIVE TOOL FOR ACCELERATING DRUG DEVELOPMENT. The cytochrome P450s (P450s) are a family of enzymes that are perhaps the most versatile biological catalysts known. DNA shuffling is an emerging technique that takes the genes encoding families of enzymes and creates libraries of catalysts with both improved and novel properties. We will obtain proof of concept that shuffled P450 libraries can be screened and optimized for use as biocatalys ....BIOCATALYSTS MINED FROM CYTOCHROME P450 LIBRARIES: AN INNOVATIVE TOOL FOR ACCELERATING DRUG DEVELOPMENT. The cytochrome P450s (P450s) are a family of enzymes that are perhaps the most versatile biological catalysts known. DNA shuffling is an emerging technique that takes the genes encoding families of enzymes and creates libraries of catalysts with both improved and novel properties. We will obtain proof of concept that shuffled P450 libraries can be screened and optimized for use as biocatalysts in drug development. The methodologies developed here will overcome two critical bottlenecks in current drug development: the optimisation and metabolic profiling of new drug candidates. This will yield important benefits in accelerating the optimisation and safety testing of drugs under development.Read moreRead less
Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase. Enzymes have the ability to catalyse biological reactions rapidly as a consequence of their unique three-dimensional structures. We seek to define the structures of a family of metalloenzymes that are required in most living organisms to activate hormones, degrade unwanted proteins or recycle the protein building blocks for further synthesis. We shall use this information to enhance a second ....Understanding and changing the mechanism of an enzyme: converting a peptidase to a phosphotriesterase. Enzymes have the ability to catalyse biological reactions rapidly as a consequence of their unique three-dimensional structures. We seek to define the structures of a family of metalloenzymes that are required in most living organisms to activate hormones, degrade unwanted proteins or recycle the protein building blocks for further synthesis. We shall use this information to enhance a second function of these enzymes, namely their ability to break down organophosphorus-containing insecticides and nerve agents. Ultimately, the structural information resulting from this project may be used in drug design to regulate blood pressure and in engineering proteins for bioremediation.Read moreRead less
Organophosphate pesticide degradation: evolved enzymes and biomimetics for bioremediation and medicine. Organophosphate (OP) pesticides are an indispensable part of modern agriculture - their use results in dramatically increased crop yields. However, they are toxic and can damage the environment and cause significant health problems. Enzymes are currently being used to treat runoff water that is contaminated with OPs. The same enzymes also have the potential to aid in the treatment of OP poison ....Organophosphate pesticide degradation: evolved enzymes and biomimetics for bioremediation and medicine. Organophosphate (OP) pesticides are an indispensable part of modern agriculture - their use results in dramatically increased crop yields. However, they are toxic and can damage the environment and cause significant health problems. Enzymes are currently being used to treat runoff water that is contaminated with OPs. The same enzymes also have the potential to aid in the treatment of OP poisoning. However, OP degrading enzymes could be improved in many ways - we will evolve these enzymes to enhance their catalytic properties - to enable them to act more efficiently on an increased number of OPs. Read moreRead less
The toxins of water-borne cyanobacteria: regulation and exploitation of their biosynthesis. Water quality is a major concern in Australia, as is the global need for new natural products with antibiotic activity. The mechanisms by which cyanobacteria produce toxins that reduce the quality of water may very well be the answer to the lack of novel medicinal compounds currently being discovered in nature. Encompassed in this one program are the aims of ameliorating the effects of toxic algal blooms ....The toxins of water-borne cyanobacteria: regulation and exploitation of their biosynthesis. Water quality is a major concern in Australia, as is the global need for new natural products with antibiotic activity. The mechanisms by which cyanobacteria produce toxins that reduce the quality of water may very well be the answer to the lack of novel medicinal compounds currently being discovered in nature. Encompassed in this one program are the aims of ameliorating the effects of toxic algal blooms as well as introducing the means for the design and synthesis of a range of novel bioactive products. The benefits include better water quality and biosafety management options, a new generation of drug design and discovery, and the associated transformation of environmental and medical research and education in Australia.Read moreRead less