New approaches to functional and structural genomics. Genome sequencing has revealed complete sets of macromolecules that make up our cells. We now need to learn how these macromolecules work together in a coordinated fashion. The proposed research will lead to the discovery of new biological molecules, interactions and processes essential for the function of cells, identify new therapeutic targets and strategies to combat disease, identify new concepts in bio- and nanotechnology, and train new ....New approaches to functional and structural genomics. Genome sequencing has revealed complete sets of macromolecules that make up our cells. We now need to learn how these macromolecules work together in a coordinated fashion. The proposed research will lead to the discovery of new biological molecules, interactions and processes essential for the function of cells, identify new therapeutic targets and strategies to combat disease, identify new concepts in bio- and nanotechnology, and train new interdisciplinary researchers. It will underpin the National Research Priorities (Frontier Technologies for Building and Transforming Australian Industries, and Promoting and Maintaining Good Health) and help Australia capitalise on a plethora of opportunities for future economic and health benefits.Read moreRead less
Enabling Technologies for Motion Corrected Positron Emission Tomography (PET) of Unanaesthetized Laboratory Animals. Small animal molecular imaging is a powerful tool in biological research and drug discovery. Anaesthesia is routinely used to avoid motion distortion, but can profoundly alter the biological process studied. This research will enable quantitative imaging of neurobiological phenomena in awake laboratory animals. It will create new opportunities for Australian basic researchers to ....Enabling Technologies for Motion Corrected Positron Emission Tomography (PET) of Unanaesthetized Laboratory Animals. Small animal molecular imaging is a powerful tool in biological research and drug discovery. Anaesthesia is routinely used to avoid motion distortion, but can profoundly alter the biological process studied. This research will enable quantitative imaging of neurobiological phenomena in awake laboratory animals. It will create new opportunities for Australian basic researchers to use innovative technology with expected high economic potential, and benefit small biotech companies by facilitating pre-clinical and clinical development of new pharmaceuticals. The new motion tracking and image reconstruction technologies developed will strengthen Australia's leading position in engineering and biomedical systems development.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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A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to ....A study of the nongenomic action of Vitamin D: proposed role of the nuclear VDR and downstream signalling molecules. Vitamin D (1,25D) activates genes in the nucleus through the vitamin D receptor (VDR). 1,25D can also elicit rapid responses at the plasma membrane. This action is critical to the activation of nuclear genes. We hypothesise that a proportion of the nuclear VDR is located at the plasma membrane where it stimulates downstream signalling molecules eg Ras, ERK1/2 and ERK5. We plan to explore this hypothesis and to identify the signalling molecules. We will also investigate our novel finding that a specific Ras isoform is involved in ERK5 activation. The work will provide new information on signalling pathways.Read moreRead less
Structural studies on the mitochondrial protein import machinery. Proteins transported across biological membranes are generally synthesized as precursors with signal sequences. These signal sequences are decoded by one of a number of membrane-specific protein transport machinery, but how this decoding occurs is largely unknown. This proposal aims to understand the structural basis of protein import into the mitochondrion, a poorly understood biological process. This study will enhance signif ....Structural studies on the mitochondrial protein import machinery. Proteins transported across biological membranes are generally synthesized as precursors with signal sequences. These signal sequences are decoded by one of a number of membrane-specific protein transport machinery, but how this decoding occurs is largely unknown. This proposal aims to understand the structural basis of protein import into the mitochondrion, a poorly understood biological process. This study will enhance significantly our understanding of mitochondrial biology, and will also have ramifications for other areas of protein transport.Read moreRead less
Guanylate cyclases - an expanding family critical in plant growth and development. The enzyme guanylate cyclase (GC) forms an important signalling molecule. We have identified unique GC molecules from higher plants. We shall use strategic basic research to determine the biological importance of these novel molecules in plant growth and development. We have formed an international team to achieve these goals and also to develop strong scientific links between Australia and other countries such as ....Guanylate cyclases - an expanding family critical in plant growth and development. The enzyme guanylate cyclase (GC) forms an important signalling molecule. We have identified unique GC molecules from higher plants. We shall use strategic basic research to determine the biological importance of these novel molecules in plant growth and development. We have formed an international team to achieve these goals and also to develop strong scientific links between Australia and other countries such as South Africa. The outcomes will provide new insight into the biological function of the novel GCs. Consequently, the new knowledge is critical to the development of novel biotechnological approaches to benefit sustainable agriculture in Australia.Read moreRead less
Regulation of the actin cytoskeleton by LIM kinase 2. Because the regulation of actin cytoskeleton is essential for many cellular processes including cell motility and the normal function of neurons, it is of great importance to understand its regulation. Elucidation of the molecular and biological mechanisms underlying the actin cytoskeleton including cell motility may enable the identification of novel therapeutic targets for the treatment of diseases such as cancer metastasis, Alzheimer disea ....Regulation of the actin cytoskeleton by LIM kinase 2. Because the regulation of actin cytoskeleton is essential for many cellular processes including cell motility and the normal function of neurons, it is of great importance to understand its regulation. Elucidation of the molecular and biological mechanisms underlying the actin cytoskeleton including cell motility may enable the identification of novel therapeutic targets for the treatment of diseases such as cancer metastasis, Alzheimer disease (AD) and/or Multiple Sclerosis (MS) in which the regulation of the actin cytoskeleton is affected.
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Analysis of the Role of Snapin in the Regulation of SNARE Complex Assembly. The aims of the proposed studies are to investigate the role played by a protein, snapin in the trafficking of membranes and cargo proteins between different compartments inside mammalian cells. Membrane trafficking is a fundamental cellular process that requires a family of related molecules termed SNARES. We have recently discovered that snapin interacts with certain members of the SNARE family, implying a critical rol ....Analysis of the Role of Snapin in the Regulation of SNARE Complex Assembly. The aims of the proposed studies are to investigate the role played by a protein, snapin in the trafficking of membranes and cargo proteins between different compartments inside mammalian cells. Membrane trafficking is a fundamental cellular process that requires a family of related molecules termed SNARES. We have recently discovered that snapin interacts with certain members of the SNARE family, implying a critical role in membrane trafficking. The proposed studies will provide important new insights into the molecular mechanisms underlying the function of both snapin and SNAREs, and membrane trafficking in general.Read moreRead less
Gain modulation and stability in biological neural systems. This project is relevant to the National Research Priority area of Frontier Technologies and addresses fundamental cross-disciplinary issues of control and information processing in large, distributed neural systems that are at the cutting edge of intelligent processing systems. Applications are in rapidly growing fields of robotics, machine learning, adaptive control and intelligent systems, all with applications in diverse areas of ec ....Gain modulation and stability in biological neural systems. This project is relevant to the National Research Priority area of Frontier Technologies and addresses fundamental cross-disciplinary issues of control and information processing in large, distributed neural systems that are at the cutting edge of intelligent processing systems. Applications are in rapidly growing fields of robotics, machine learning, adaptive control and intelligent systems, all with applications in diverse areas of economic importance. Applications to cochlear implant speech processing will provide benefit for the hearing impaired. The project will provide students with training at an international level within Australia, thus helping ensure Australia maintains and extends its science and technology base into the futureRead moreRead less
Molecular pumps and metabolism: regulatory interactions that control metal uptake and metabolism in bacteria. ABC (ATP-Binding Cassette) transporters are ubiquitous pumps that transport small molecules into and out of cells. This project investigates the novel roles of small-molecule-binding domains in the protein machine that drives the transporters for molybdenum and iron. They are predicted to interact with regulatory proteins and integrate transport with metabolism. It will provide insights ....Molecular pumps and metabolism: regulatory interactions that control metal uptake and metabolism in bacteria. ABC (ATP-Binding Cassette) transporters are ubiquitous pumps that transport small molecules into and out of cells. This project investigates the novel roles of small-molecule-binding domains in the protein machine that drives the transporters for molybdenum and iron. They are predicted to interact with regulatory proteins and integrate transport with metabolism. It will provide insights into metal trafficking and characterize gene regulatory networks that are important for bacterial pathogenicity and biological nitrogen fixation.Read moreRead less