Structural Determinants of an Intracellular Calcium Store. Understanding the molecular interactions between key proteins in calcium signalling in muscle and the heart will allow calcium signalling to be used as a platform for a variety of purposes. These include reducing the debilitating effects of changes in calcium signalling and muscle performance in aging and in genetically- or drug-induced disorders. The project will have benefits for Australian biotechnology since it will facilitate the de ....Structural Determinants of an Intracellular Calcium Store. Understanding the molecular interactions between key proteins in calcium signalling in muscle and the heart will allow calcium signalling to be used as a platform for a variety of purposes. These include reducing the debilitating effects of changes in calcium signalling and muscle performance in aging and in genetically- or drug-induced disorders. The project will have benefits for Australian biotechnology since it will facilitate the design of novel compounds for treating muscle disorders in animals and humans, for improving meat quality and for use as insecticides. The project will facilitate graduate and undergraduate training in basic science with exposure to biotechnology, through our commercial partner Biotron.Read moreRead less
Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behav ....Discovering mechanisms of primary embryonic tissue migration through live cell imaging and novel genetic approaches. The studies proposed here will provide concepts and knowledge about the molecular basis of cell migration that will impact on diverse aspects of human health, such as the causes and nature of tumour metastasis and our understanding of the developmental basis of birth defects. In addition, understanding cell migration mechanisms will allow us to better predict or control the behaviour of therapeutic stem cells introduced into the body.Read moreRead less
Mechanism of higher-order chromatin formation and its role in controlling gene expression. The organization of genomic DNA into chromatin has solved one of the most difficult engineering problems required for the development of a multicellular organism; the compaction of over two meters DNA into a cell almost one millionth this size. Importantly, this compaction of the genome into chromatin has also been exploited by the cell to regulate the expression of genes. The aim of this investigation is ....Mechanism of higher-order chromatin formation and its role in controlling gene expression. The organization of genomic DNA into chromatin has solved one of the most difficult engineering problems required for the development of a multicellular organism; the compaction of over two meters DNA into a cell almost one millionth this size. Importantly, this compaction of the genome into chromatin has also been exploited by the cell to regulate the expression of genes. The aim of this investigation is to elucidate how genes are assembled into complex active or inactive chromatin structures by employing a novel in vitro system. This information will have important implications for gene therapy strategies.
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The Dynamic Control of Chromatin Structure. A human chromosome is a highly heterogeneous global structure because along its axis, it folds to different extents to form either highly compacted domains that repress the expression of genes or less condensed regions that enable genes to be turned on. Changes to the structure or stability of chromosomes, and the corresponding alterations to gene expression, have been linked to many diseases states like defects in human development and cancer. This s ....The Dynamic Control of Chromatin Structure. A human chromosome is a highly heterogeneous global structure because along its axis, it folds to different extents to form either highly compacted domains that repress the expression of genes or less condensed regions that enable genes to be turned on. Changes to the structure or stability of chromosomes, and the corresponding alterations to gene expression, have been linked to many diseases states like defects in human development and cancer. This study will uncover the underpinning mechanism of how our chromosomes are organised into distinct functional domains, which may offer the potential to develop new strategies to correct chromosomal abnormalities.
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The Shape of Plants; Discovering factors that control morphology by organizing the cytoskeleton. Understanding how plants generate the huge diversity of shapes seen in nature is both a scientific challenge and a biotechnological opportunity. Microtubules dominate cell architecture, providing dynamic, yet rigid, frameworks for defining or changing growth polarity. We recently discovered and cloned MOR1, a gene that is essential for organizing microtubules and controlling morphogenesis. This place ....The Shape of Plants; Discovering factors that control morphology by organizing the cytoskeleton. Understanding how plants generate the huge diversity of shapes seen in nature is both a scientific challenge and a biotechnological opportunity. Microtubules dominate cell architecture, providing dynamic, yet rigid, frameworks for defining or changing growth polarity. We recently discovered and cloned MOR1, a gene that is essential for organizing microtubules and controlling morphogenesis. This places us in a strong position to resolve a long-standing mystery: how are microtubules organized? We intend to define MOR1's structural attributes, identify its interacting proteins and innovate an ambitious screen for additional genes that have related functions. This project should stimulate new ideas and applications.Read moreRead less
CesA (cellulose synthase) genes of Arabidopsis; all doing the same job or specialists cooperating to make the most abundant biopolymer. The biosphere makes more cellulose than any other polymer with fibre industries depending on its physical properties and atmospheric carbon dioxide levels depending on its stability as a carbon sink. Demonstrations that cellulose production needs CesA genes drove recent progress in elucidating the mechanism of synthesis. CesA proteins all look very similar but i ....CesA (cellulose synthase) genes of Arabidopsis; all doing the same job or specialists cooperating to make the most abundant biopolymer. The biosphere makes more cellulose than any other polymer with fibre industries depending on its physical properties and atmospheric carbon dioxide levels depending on its stability as a carbon sink. Demonstrations that cellulose production needs CesA genes drove recent progress in elucidating the mechanism of synthesis. CesA proteins all look very similar but if all do the same job, why do plants need so many and why do none seem redundant? We will make gene interchanges in transgenic plants, build chimeric genes and identify where each CesA protein operates. This will identify their individual and cooperative contributions to cellulose production.Read moreRead less
Role of a novel zinc-binding motif in the structure-function of deubiquitinating enzymes. The ubiquitin pathway destroys many proteins that control cell function and growth, by attaching ubiquitin to them and marking them for degradation. Deubiquitinating enzymes (DUBs) regulate protein destruction by controlling the amount of ubiquitin attached. DUBs and the ubiquitin pathway can also be manipulated in biotechnology applications. However, very little is known about the structure/function of DUB ....Role of a novel zinc-binding motif in the structure-function of deubiquitinating enzymes. The ubiquitin pathway destroys many proteins that control cell function and growth, by attaching ubiquitin to them and marking them for degradation. Deubiquitinating enzymes (DUBs) regulate protein destruction by controlling the amount of ubiquitin attached. DUBs and the ubiquitin pathway can also be manipulated in biotechnology applications. However, very little is known about the structure/function of DUBs. We have identified a new zinc-binding motif in DUBs, and we will explore how this contributes to their structure, and interactions with other proteins. This will significantly enhance our knowledge of how DUBs function in both biotechnology and in controlling cell function.Read moreRead less
Cellular signals controlling oocyte activation. This research will significantly advance our understanding of the basic biological processes that underpin the fertility rate of all mammals and are key to the immediate and future health and well-being of Australian landscape and society. Understanding the processes that maintain healthy quiescent oocytes over many years before activation and subsequent growth will enable development of methods of increasing productivity in domestic animals and en ....Cellular signals controlling oocyte activation. This research will significantly advance our understanding of the basic biological processes that underpin the fertility rate of all mammals and are key to the immediate and future health and well-being of Australian landscape and society. Understanding the processes that maintain healthy quiescent oocytes over many years before activation and subsequent growth will enable development of methods of increasing productivity in domestic animals and enhancing fertility in endangered species. Knowledge of these cellular mechanisms will underpin biotechnology platforms necessary for novel methods of feral animal population control thus contributing at multiple levels to an economically sustainable Australia.Read moreRead less
Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. ....Protein degradation in mammals. One mechanism by which the regulation of protein turnover occurs is the balance between the activity of enzymes responsible for the ubiquitination and deubiquitination of target proteins. The majority of targets of this second family of enzymes are unknown. This project proposes a method for the identification of the targets of two specific mammalian deubiquitinating enzymes in order to understand their function and to begin to explore this new research field. Knowledge about this new aspect of protein degradation could provide a powerful tool to test the effect of the stabilisation or removal of specific proteins in the cell and also to develop new technologies in protein production.Read moreRead less
A unified model of amino acid homeostasis. This project aims to develop a unified model of amino acid homeostasis in mammalian cells and apply it to brain cells. The model will be underpinned by a mathematical algorithm that allows predicting amino acid levels in the cytosol based on fundamental parameters such as transport and metabolism. This project should provide the significant benefit of enabling the prediction of essential functions such as cell growth and survival.