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Nanoprobe and Microprobe Structural and Spectroscopic Studies in Biomedical Research. Breakthrough microprobe and nanoprobe technologies, involving X-ray, visible and infrared light can focus into different components of mammalian cells in order to interrogate the biochemistry that is occurring therein. Each of the different wavelengths of light provides complementary biochemical information that enables multi-layered information on changes in cells that occur as a function of drug treatments a ....Nanoprobe and Microprobe Structural and Spectroscopic Studies in Biomedical Research. Breakthrough microprobe and nanoprobe technologies, involving X-ray, visible and infrared light can focus into different components of mammalian cells in order to interrogate the biochemistry that is occurring therein. Each of the different wavelengths of light provides complementary biochemical information that enables multi-layered information on changes in cells that occur as a function of drug treatments and disease processes. This will provide unprecedented information as to where drugs go and how they are transformed inside cells that, in turn, may revolutionalise the way in which new drugs are designed that have higher specificity and lower side effects.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
Gold-based mitochondria targeted chemotherapeutics: mechanistic studies probing interactions with thiol and selenol containing proteins. Cancer affects one in four Australians and prostate cancer is the most commonly diagnosed and second leading cause of male cancer deaths, for which there is currently no effective treatment. Current chemotherapeutics must overcome drug resistance and lack of selectivity between tumour and normal cells. To circumvent these problems we are investigating gold-base ....Gold-based mitochondria targeted chemotherapeutics: mechanistic studies probing interactions with thiol and selenol containing proteins. Cancer affects one in four Australians and prostate cancer is the most commonly diagnosed and second leading cause of male cancer deaths, for which there is currently no effective treatment. Current chemotherapeutics must overcome drug resistance and lack of selectivity between tumour and normal cells. To circumvent these problems we are investigating gold-based compounds, which act by a novel mechanism. The research will lead to new strategies in the design of improved anticancer drugs, an important Australian research priority that will promote and maintain good health. Other benefits arise from training PhD students with interdisciplinary skills for Australian biotechnology industries.Read moreRead less
Bacterial monooxygenases as new biocatalysts. Using enzymes for synthesis of new pharmaceuticals is of increasing importance. Monooxygenases are particularly interesting because of their capacity to perform chemically difficult reactions thus increasing potential to make new pharmaceuticals. We have shown that an enormous pool of diverse and novel monooxygenases exists in naturally occurring bacteria. These enzymes are naturally important in pollutant degradation and regulating the emissions of ....Bacterial monooxygenases as new biocatalysts. Using enzymes for synthesis of new pharmaceuticals is of increasing importance. Monooxygenases are particularly interesting because of their capacity to perform chemically difficult reactions thus increasing potential to make new pharmaceuticals. We have shown that an enormous pool of diverse and novel monooxygenases exists in naturally occurring bacteria. These enzymes are naturally important in pollutant degradation and regulating the emissions of greenhouse gases. We will develop these enzymes for biotechnology by characterizing structural features that influence catalytic properties relevant to challenges in pharmaceutical synthesis. The outcomes will enable their engineering for specific applications in synthesis of new drugs.Read moreRead less
Molecular genetic analysis of genes controlling morphogenesis: Dimorphic switching in the fungus Penicillium marneffei. Fungi exist in two predominant growth forms; unicellular yeast and multicellular mould (filamentous hyphae). Some fungi can alternate between these two forms in response to environmental stimuli, a process known as dimorphic switching. The cells of these two forms have distinctive shapes and physiological capacities established by genome-wide expression patterns that are trigge ....Molecular genetic analysis of genes controlling morphogenesis: Dimorphic switching in the fungus Penicillium marneffei. Fungi exist in two predominant growth forms; unicellular yeast and multicellular mould (filamentous hyphae). Some fungi can alternate between these two forms in response to environmental stimuli, a process known as dimorphic switching. The cells of these two forms have distinctive shapes and physiological capacities established by genome-wide expression patterns that are triggered by signalling pathways. This research aims to understand the fundamental mechanisms controlling dimorphic switching using Penicillium marneffei, a model system. P. marneffei switches between yeast and filamentous forms in response to temperature. Uncovering the molecular mechanisms that control dimorphic switching has important implications for biotechnology and medicine.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
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
Molecular Genetic Analysis of Genes Regulating Metabolism in the Fungus Aspergillus nidulans. Filamentous fungi can use a wide variety of sources of carbon and nitrogen. In order to grow on these compounds metabolism is adjusted in response to changes in nutrient availability. Patterns of genome expression are altered by signalling to global regulatory genes which control the transcription of genes producing enzymes appropriate to the substrates available. This is of fundamental significance to ....Molecular Genetic Analysis of Genes Regulating Metabolism in the Fungus Aspergillus nidulans. Filamentous fungi can use a wide variety of sources of carbon and nitrogen. In order to grow on these compounds metabolism is adjusted in response to changes in nutrient availability. Patterns of genome expression are altered by signalling to global regulatory genes which control the transcription of genes producing enzymes appropriate to the substrates available. This is of fundamental significance to the physiology and development of fungi which include devastating pathogens and species used in industrial microbiology. This project aims to use the excellent molecular genetics of the model fungus Aspergillus nidulans to investigate the strategies employed and the mechanisms involved.Read moreRead less
Gating, specificity and regulation of the YggB channel protein from Corynebacterium glutamicum. The proposed research will greatly contribute to our understanding of the functioning of a bacterial membrane channel/transporter, which has played a significant role in biotechnology of commercially important amino acids. A direct national benefit will result from establishing collaboration with a leading German laboratory providing expertise in protein biochemistry and molecular microbiology not ava ....Gating, specificity and regulation of the YggB channel protein from Corynebacterium glutamicum. The proposed research will greatly contribute to our understanding of the functioning of a bacterial membrane channel/transporter, which has played a significant role in biotechnology of commercially important amino acids. A direct national benefit will result from establishing collaboration with a leading German laboratory providing expertise in protein biochemistry and molecular microbiology not available in Australia. The acquired knowledge will present an original contribution which will have a strong impact on a very competitive field of molecular microbiology and biotechnology.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