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
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
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
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 molecular biology and biochemistry of bacterial manganese oxidation. This project will further the understanding of bacterial manganese (Mn2+) oxidation. A multi-disciplinary approach will be used to further investigate the genetics and biochemistry of the Mn2+-oxidising systems of Pseudomonas putida, Leptothrix sp. and Pedomicrobium sp. This work will focus in particular on comparing the Mn2+-oxidising systems from unrelated bacteria. A combination of molecular biology, protein biochemis ....The molecular biology and biochemistry of bacterial manganese oxidation. This project will further the understanding of bacterial manganese (Mn2+) oxidation. A multi-disciplinary approach will be used to further investigate the genetics and biochemistry of the Mn2+-oxidising systems of Pseudomonas putida, Leptothrix sp. and Pedomicrobium sp. This work will focus in particular on comparing the Mn2+-oxidising systems from unrelated bacteria. A combination of molecular biology, protein biochemistry and spectroscopy will be used. This will be the first time that the enzymes of bacterial Mn2+-oxidation will have been characterised in such detail and will lead to a greater understanding of the process of bacterial manganese oxidation.Read moreRead less
High throughput engineering of genetically encodable fluorescent sensors of intracellular signalling networks. Understanding of biochemical processes in living organisms is central to biological research and drug discovery. At present, the field suffers from a chronic paucity of adequate observation methods. The proposed project represents an interdisciplinary effort to create approaches for real-time monitoring of complex cellular chemistries. This work will deliver novel technologies for use i ....High throughput engineering of genetically encodable fluorescent sensors of intracellular signalling networks. Understanding of biochemical processes in living organisms is central to biological research and drug discovery. At present, the field suffers from a chronic paucity of adequate observation methods. The proposed project represents an interdisciplinary effort to create approaches for real-time monitoring of complex cellular chemistries. This work will deliver novel technologies for use in diagnostics and drug development. It will provide vital information on the changes in cellular processes induced by malignant transformation, viral infection and aging. This work will generate both health and economic benefits for the community and have a positive impact on the international visibility of Australian biomedical research.Read moreRead less
Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in bi ....Understanding mechanistic and systemic regulation of protein prenyltransferases. The proposed research will expand our understanding of lipid-conjugating enzymes that are critical for a multitude of normal cellular functions. We seek to reveal the basic workings of cells and help to explain the development and complexity of signalling networks in eukaryotic evolution. The findings will enable us to explore and exploit the catalytic properties of these lipid-related enzymes for applications in biotechnology. The ultimate aim is to create novel technologies for protein production, modification and analysis that will accelerate the pace of discovery in protein research, basic cell and organism biology, diagnostics, biotechnology and drug discovery. Read moreRead less
Directed evolution of enzymes for bioremediation: structure function studies of bimetalloenzymes. We will evolve enzymes that degrade organophosphate pesticides (OPs) that are used in Australian agriculture. Although these OPs were designed to kill insects they are closely related to chemical warfare agents and are known to be toxic to humans. Bacteria have acquired a number of enzymes that degrade some OPs. One such enzyme has been used in field trials demonstrating its potential to degrade OP ....Directed evolution of enzymes for bioremediation: structure function studies of bimetalloenzymes. We will evolve enzymes that degrade organophosphate pesticides (OPs) that are used in Australian agriculture. Although these OPs were designed to kill insects they are closely related to chemical warfare agents and are known to be toxic to humans. Bacteria have acquired a number of enzymes that degrade some OPs. One such enzyme has been used in field trials demonstrating its potential to degrade OP residues. However, many pesticides are not removed rapidly and OP-degrading enzymes require modification(s) if they are to be useful environmental reagents - this can be achieved with directed evolution. Read moreRead less
Evolving enzymes to harness the clean energy reserves of nature. We want to improve enzymes that are used by nature to harness huge amounts of energy - the energy present in glucose, one of the most abundant materials in the biosphere. The enzymes will be evolved to efficiently produce biological power in a practically useable form rather than for the growth of the organisms from which they originated. We will use this energy to drive the synthesis of chemicals of practical value, truly green ch ....Evolving enzymes to harness the clean energy reserves of nature. We want to improve enzymes that are used by nature to harness huge amounts of energy - the energy present in glucose, one of the most abundant materials in the biosphere. The enzymes will be evolved to efficiently produce biological power in a practically useable form rather than for the growth of the organisms from which they originated. We will use this energy to drive the synthesis of chemicals of practical value, truly green chemistry. We also seek to answer questions such as: how do proteins evolve, how do enzymes work and how can biochemical pathways be optimised for industrial processes? This information will be of fundamental benefit for the use of enzymes in green chemistry, providing cleaner ways to produce important chemicals. Read moreRead less
Disulfide Bonds and Protein Folding. This work will advance our understanding of protein folding, which has important implications in biotechnology, impacting on commercial production of recombinant proteins (for pharmaceutical and biomedical applications) and on 1000s of research laboratories worldwide that use recombinant technologies. This research could also contribute to medicine (new treatments for diseases of protein misfolding like Alzheimer's), and to membrane protein structural biology ....Disulfide Bonds and Protein Folding. This work will advance our understanding of protein folding, which has important implications in biotechnology, impacting on commercial production of recombinant proteins (for pharmaceutical and biomedical applications) and on 1000s of research laboratories worldwide that use recombinant technologies. This research could also contribute to medicine (new treatments for diseases of protein misfolding like Alzheimer's), and to membrane protein structural biology. This work could yield economic benefits in the long-term through patentable outcomes and will benefit the community by producing high impact research papers, providing training to Australians and forging links with renowned international scientists.Read moreRead less