A sustainable cellular factory for the production of antibiotics by photosynthetic bacteria. The range and rate of natural product discovery is the limiting factor in developing new pharmaceuticals. Traditional methods for the screening of these compounds or for their chemical synthesis are rapidly becoming inadequate as an increasing number of specific therapies, for cancers and infectious diseases for instance, are required. The research proposed will enable the design and production of "unnat ....A sustainable cellular factory for the production of antibiotics by photosynthetic bacteria. The range and rate of natural product discovery is the limiting factor in developing new pharmaceuticals. Traditional methods for the screening of these compounds or for their chemical synthesis are rapidly becoming inadequate as an increasing number of specific therapies, for cancers and infectious diseases for instance, are required. The research proposed will enable the design and production of "unnatural" products, including novel antibiotics, via combinatorial biosynthesis in photosynthetic microorgansims. The outcomes include graduate student training and Australian innovation in an enormous global market that is awaiting the next generation of medicines and associated pharmaceutical production technologies.Read moreRead less
Exploiting novel yeast attributes to produce industrial strains with better fermentative and processing qualities. Food and beverage fermentations are problematic processes, largely due to limitations of the yeast being used. This laboratory has indentified in individual yeast strains highly desirable fermentative characteristics or else the ability to over-produce compounds that benefit product processing. Pursuing the commercial potential of these findings is the specific objective of this pro ....Exploiting novel yeast attributes to produce industrial strains with better fermentative and processing qualities. Food and beverage fermentations are problematic processes, largely due to limitations of the yeast being used. This laboratory has indentified in individual yeast strains highly desirable fermentative characteristics or else the ability to over-produce compounds that benefit product processing. Pursuing the commercial potential of these findings is the specific objective of this proposal. Thus we will extend our collaboration with Coopers Brewery through this new project area with the aims of a) producing optimised, hybrid (non-GMO) strains with combinations of desirable fermentation properties, b) develop novel processing or quality-enhancing treatments while c) generating a high caliber PhD graduate with extensive industry experience.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
Enhancing Grain Yield Potential and Quality of Lupin. Sustainability of wheat production in Western Australia depends on the continued use of legumes, specifically lupins, in farming systems. The low returns to growers for lupins has jeopardised these sustainable systems. This project aims to gather new information to develop novel genetic strategies to increase yield potential and modify seed composition in lupins, enhancing their commercial worth.
Engineering of anti-platelet antibodies for the diagnosis and therapy of infants with bleeding disorders. Foeto-maternal alloimmune thrombocytopenia (FMAIT) is a serious clinical condition where infants suffer potentially fatal bleeding disorders from 14 weeks gestation to 1-2 weeks post delivery. The cause of the disease is through maternal antibodies destroying foetal platelets. Our aim is to produce human antibodies, which will be used as diagnostic agents to screen for the condition in preg ....Engineering of anti-platelet antibodies for the diagnosis and therapy of infants with bleeding disorders. Foeto-maternal alloimmune thrombocytopenia (FMAIT) is a serious clinical condition where infants suffer potentially fatal bleeding disorders from 14 weeks gestation to 1-2 weeks post delivery. The cause of the disease is through maternal antibodies destroying foetal platelets. Our aim is to produce human antibodies, which will be used as diagnostic agents to screen for the condition in pregnant women, and to further develop such antibodies for therapy. Identification of mothers at risk of FMAIT and the development of a specific therapy are vital to the management and prevention of this serious condition.Read moreRead less