Intravital super-resolution imaging via Stimulated Emission Depletion microscopy (STED)-microendoscopy. We will develop a new technology to enable the imaging of sub-cellular structures within a biological specimen, with super-resolution. This intravital super-resolution imaging technology will build off world leading techniques to image objects with super-resolution and to perform this within a specimen, with minimal invasion. The broad ramifications of this technology apply to biology, medical ....Intravital super-resolution imaging via Stimulated Emission Depletion microscopy (STED)-microendoscopy. We will develop a new technology to enable the imaging of sub-cellular structures within a biological specimen, with super-resolution. This intravital super-resolution imaging technology will build off world leading techniques to image objects with super-resolution and to perform this within a specimen, with minimal invasion. The broad ramifications of this technology apply to biology, medical science, imaging and sensing. Important applications include the early detection of debilitating diseases and the advancement of understanding of cellular biology. This research will raise Australia's profile as a world leader in science and technology, building on our emerging presence in the biophysical sciences.Read moreRead less
Sequencing the mammalian transcriptome in toto. The mammalian genome projects have provided a huge leap forward for biological research by giving the framework to study genes on a global scale. This project will provide human genome project scale information for every major tissue in mammals and will provide the research community with a world class resource to further genomic research. It will also investigate parts of gene regulation which have been invisible to researchers in the past. Discov ....Sequencing the mammalian transcriptome in toto. The mammalian genome projects have provided a huge leap forward for biological research by giving the framework to study genes on a global scale. This project will provide human genome project scale information for every major tissue in mammals and will provide the research community with a world class resource to further genomic research. It will also investigate parts of gene regulation which have been invisible to researchers in the past. Discovering these rules will provide novel insights in pathology with a genetic component and provide a further boost to biotechnological approaches to obtain expression of specific sets of genes in model systems. Read moreRead less
Discovery and characterization of new classes of small regulatory RNAs in mammals. The project will reaffirm and enhance Australian leadership in the most rapidly developing area of molecular biological and genetic research, by the application of ultra high-throughput sequencing technologies to discovery of regulatory RNAs, thereby to identify the characteristics of important regulatory pathways that underpin mammalian development, brain function and species diversity. The results of this resear ....Discovery and characterization of new classes of small regulatory RNAs in mammals. The project will reaffirm and enhance Australian leadership in the most rapidly developing area of molecular biological and genetic research, by the application of ultra high-throughput sequencing technologies to discovery of regulatory RNAs, thereby to identify the characteristics of important regulatory pathways that underpin mammalian development, brain function and species diversity. The results of this research will have wide implications and applications in biotechnology, genetic engineering, animal breeding, medical science and advanced informatics.Read moreRead less
High resolution single particle analysis of biological macromolecules. One of the great challenges of cell biology is to increase the rate of atomic resolution structure determination, particularly of membrane proteins and macromolecular assemblies. The current rate-limiting step is high quality crystal production. Our goal is to prove that protein structures can be determined to atomic resolution by single-particle analysis. 3D structures will be produced by computationally aligning high-resolu ....High resolution single particle analysis of biological macromolecules. One of the great challenges of cell biology is to increase the rate of atomic resolution structure determination, particularly of membrane proteins and macromolecular assemblies. The current rate-limiting step is high quality crystal production. Our goal is to prove that protein structures can be determined to atomic resolution by single-particle analysis. 3D structures will be produced by computationally aligning high-resolution electron microscope images of individual, randomly oriented molecules. The importance of this project is highlighted by the fact over 120,000 protein sequences are already databased, a number set to increase rapidly as new genome sequencing projects are completed.
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Advanced optical tweezers technologies for biophysical measurements. While much is understood about the fundamental unit of life, the living cell, such as their behaviour and their biochemistry and genetics, the interface between these two is only poorly known. We will use optical tweezers, which can trap and move microscopic objects without physical contact, to measure forces on the molecular and cellular scale to study the mechanical properties of cells and biomolecules, including molecular mo ....Advanced optical tweezers technologies for biophysical measurements. While much is understood about the fundamental unit of life, the living cell, such as their behaviour and their biochemistry and genetics, the interface between these two is only poorly known. We will use optical tweezers, which can trap and move microscopic objects without physical contact, to measure forces on the molecular and cellular scale to study the mechanical properties of cells and biomolecules, including molecular motors, which are Nature's own nanomachines, advanced our knowledge of the fundamental machinery of life.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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560657
Funder
Australian Research Council
Funding Amount
$740,000.00
Summary
Ultra-High Resolution NMR Imaging System for Nanotechnology including Nanobiotechnology. The ultra-high resolution imaging NMR spectrometer at the centre of this application is a generation ahead of comparable facilities in Australia and will extend the research capacity of numerous research groups comprising in excess of 50 academics and postgraduate students. The aims and significance of this infrastructure lie in it being one of the centrepieces of the partner institutions' aspirations to tak ....Ultra-High Resolution NMR Imaging System for Nanotechnology including Nanobiotechnology. The ultra-high resolution imaging NMR spectrometer at the centre of this application is a generation ahead of comparable facilities in Australia and will extend the research capacity of numerous research groups comprising in excess of 50 academics and postgraduate students. The aims and significance of this infrastructure lie in it being one of the centrepieces of the partner institutions' aspirations to take Australia to the cutting edge of nanotechnology and cognate disciplines many of which are areas of national priority. The expected manifold outcomes include research of the highest rank into fundamental problems of drug development through to applied outcomes such as new nanomaterials and improved horticulture/fruit preservation.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
Plant heterotrimeric G proteins: new roles in defence, stomatal control and ABA perception. Agriculture is an important economic activity in Australia that results in considerable export revenues. Two of the major problems facing agriculture around the globe are the incidence of diseases and the scarcity of water. Agricultural losses caused by plant pathogens and low water availability account for billions of dollars every year and have profound economic and social implications. Water is an extr ....Plant heterotrimeric G proteins: new roles in defence, stomatal control and ABA perception. Agriculture is an important economic activity in Australia that results in considerable export revenues. Two of the major problems facing agriculture around the globe are the incidence of diseases and the scarcity of water. Agricultural losses caused by plant pathogens and low water availability account for billions of dollars every year and have profound economic and social implications. Water is an extremely scarce resource in Australia and periodic droughts inflict immense losses to the Australian agricultural sector. Our research will explore new and cleaner strategies to provide crop protection as well as to increase water use efficiency.Read moreRead less