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
Final frontier in computational modelling of movement. This project aims to create the computational models and methods needed to advance current understanding of musculoskeletal function during movement. Humans must maintain their capacity to move in order to maintain quality-of-life. Predictive modelling is potentially the most powerful approach for understanding musculoskeletal function during movement. Current computational methods are too slow and unreliable to deliver predictive simulation ....Final frontier in computational modelling of movement. This project aims to create the computational models and methods needed to advance current understanding of musculoskeletal function during movement. Humans must maintain their capacity to move in order to maintain quality-of-life. Predictive modelling is potentially the most powerful approach for understanding musculoskeletal function during movement. Current computational methods are too slow and unreliable to deliver predictive simulations of movement using realistic models of muscle and joint anatomy. This project expects to create the next generation of methods and algorithms needed to enable predictive modelling of movement. Predictive simulations will provide new insights into how muscles stabilise and control movements of the spine, pelvis and lower limbs during daily activities such as walking.Read moreRead less
Accurate Prediction of Safe Life of Buried Pipelines. Failures of buried pipes are disastrous, causing severe consequences and disruptions. They often reoccur because the fundamental cause-effect relation for pipe failures has not been fully understood and hence the safe life of pipelines cannot be reliably predicted. The aim of this research is to develop a new theory to predict pipe failures, based on a fundamental analysis of pipe behaviour and failure mechanisms and a reliability approach. T ....Accurate Prediction of Safe Life of Buried Pipelines. Failures of buried pipes are disastrous, causing severe consequences and disruptions. They often reoccur because the fundamental cause-effect relation for pipe failures has not been fully understood and hence the safe life of pipelines cannot be reliably predicted. The aim of this research is to develop a new theory to predict pipe failures, based on a fundamental analysis of pipe behaviour and failure mechanisms and a reliability approach. The outcomes will be a suite of models and solutions that will advance knowledge in deterioration science and failure theory. They will provide a sustainable solution to the intelligent management of buried pipelines throughout the world.Read 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
Fundamental theoretical and experimental investigation of cartilage mechanics. Arthritis and chronic joint symptoms are one of the leading causes of disability in the community, yet a fundamental understanding of joint mechanics has yet to be realised. The aim of this project is to develop a new state-of-the-art mathematical model describing cartilage behaviour in humans. The model will explain how activities like walking maintain healthy cartilage by transferring growth factors through the tiss ....Fundamental theoretical and experimental investigation of cartilage mechanics. Arthritis and chronic joint symptoms are one of the leading causes of disability in the community, yet a fundamental understanding of joint mechanics has yet to be realised. The aim of this project is to develop a new state-of-the-art mathematical model describing cartilage behaviour in humans. The model will explain how activities like walking maintain healthy cartilage by transferring growth factors through the tissue, and quantitatively explain how wear is minimised in cartilage through weeping lubrication. This model will progress our understanding of cartilage mechanics in health and disease, and so help Australians age well and productively.Read moreRead less
The response of beams subjected to axial load and lateral soil movements. Beams (piles, soil nails, and pipelines) are not only subjected to axial (vertical, axial and longitudinal)loading, but often withstand simultaneous lateral loading, due to either explicit structural loads, or due to loads induced by movement of the soils in which they are founded. Bridge piles adjacent to an approach embankment are one example. This project will provide experimental evidence to assist with the estimation ....The response of beams subjected to axial load and lateral soil movements. Beams (piles, soil nails, and pipelines) are not only subjected to axial (vertical, axial and longitudinal)loading, but often withstand simultaneous lateral loading, due to either explicit structural loads, or due to loads induced by movement of the soils in which they are founded. Bridge piles adjacent to an approach embankment are one example. This project will provide experimental evidence to assist with the estimation of capacity, axial and shear resistance, the validation of unified solutions for beams subjected to simultaneous lateral soil movements and axial loads. Such experimental evidence and analytical solutions are not currently available. The evidence will also assist with solving a contradictory, existing design principle, which will lead to an economic and efficient design approach.Read moreRead less
Microstructure-Based Computational Homogenization of Geomaterials. This project seeks to establish a basis for virtual testing of materials. This type of non-destructive testing has numerous applications of obvious benefit to society and will contribute to the continued growth and development of a large number of industries in Australia and worldwide. The methods developed will allow for cheaper, faster, and more accurate testing of materials. The outcomes of the project can find direct applicat ....Microstructure-Based Computational Homogenization of Geomaterials. This project seeks to establish a basis for virtual testing of materials. This type of non-destructive testing has numerous applications of obvious benefit to society and will contribute to the continued growth and development of a large number of industries in Australia and worldwide. The methods developed will allow for cheaper, faster, and more accurate testing of materials. The outcomes of the project can find direct application in civil engineering as well as in environmental, mining and petroleum engineering which together make up a significant portion of the nation's industry.Read moreRead less