Synthesis of substrate analogues for probing catalytic mechanisms and specificity of enzymes involved in the metabolism of plant polysaccharides. The project is aimed at strengthening collaborations between research groups in Adelaide and France, with the specific objective of synthesizing substrate analogues as probes of enzymatic mechanisms and substrate specificity in polysaccharide hydrolases and synthases of barley. The chemical expertise resides in France, while the enzymatic work will be ....Synthesis of substrate analogues for probing catalytic mechanisms and specificity of enzymes involved in the metabolism of plant polysaccharides. The project is aimed at strengthening collaborations between research groups in Adelaide and France, with the specific objective of synthesizing substrate analogues as probes of enzymatic mechanisms and substrate specificity in polysaccharide hydrolases and synthases of barley. The chemical expertise resides in France, while the enzymatic work will be conducted largely in Australia. Exchange of research staff, particularly at the postgraduate student and research associate levels, is considered essential to capture the benefits of the complementary expertise and to extend an existing international collaboration. The target enzymes are of central importance in cell wall metabolism during development of higher plants.Read moreRead less
Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only pro ....Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only provide fundamental information on catalytic mechanisms, but will also provide opportunities to manipulate enzyme specificity. Further, site-directed mutagenesis of the enzymes will be used to generate glycosynthases, which will be evaluated for their ability to synthesise novel oligosaccharide and polysaccharide products, some of which might show immunomodulating activity.Read moreRead less
Characterisation of the oxygen-sensing asparaginyl hydroxylase, FIH-1, and hydroxylase-specific antagonists. This research will provide fundamental information on how cells and whole organisms can sense and respond accordingly to oxygen deficiency. This information is fundamental for our understanding of embryo development and adult life in different environments, and central to the diagnosis and treatment of diseases such as stroke, cardiovascular disease, and cancer. This research will contrib ....Characterisation of the oxygen-sensing asparaginyl hydroxylase, FIH-1, and hydroxylase-specific antagonists. This research will provide fundamental information on how cells and whole organisms can sense and respond accordingly to oxygen deficiency. This information is fundamental for our understanding of embryo development and adult life in different environments, and central to the diagnosis and treatment of diseases such as stroke, cardiovascular disease, and cancer. This research will contribute to our basic knowledge of these processes, provide invaluable information about the specific genes and proteins involved, and provide direct information about the therapeutic potential of specific drugs or inhibitors designed to target this oxygen response in human disease.Read moreRead less
Polysaccharide Synthase Genes in Agro-Industrial Applications. Achievement of the project aims will generate valuable intellectual property and meet National Research Priorities by: enhancing our knowledge base for the production of renewable bio-fuels from crop residues, for an environmentally sustainable Australia; developing preventative healthcare through adoption of healthier diets, rich in non-starchy cell wall polysaccharides that help reduce the incidence and severity of cardiovascular d ....Polysaccharide Synthase Genes in Agro-Industrial Applications. Achievement of the project aims will generate valuable intellectual property and meet National Research Priorities by: enhancing our knowledge base for the production of renewable bio-fuels from crop residues, for an environmentally sustainable Australia; developing preventative healthcare through adoption of healthier diets, rich in non-starchy cell wall polysaccharides that help reduce the incidence and severity of cardiovascular disease, obesity, diabetes and some cancers; and by developing breakthrough science in emerging agricultural technologies. The alliance will foster an intellectual environment to provide world-class basic research outcomes and training of highly skilled graduates, thereby contributing to the 'knowledge nation'.Read moreRead less
Regulation of autophagy dependent cell and tissue deletion. This project aims to elucidate novel mechanisms that regulate autophagy-depdendent cell death during animal development. It will combine the power of Drosophila genetics with multidisciplinary approaches, such as proteomics, bioinformatics and cell biology. Given the conserved nature of autophagy the oucomes will provide highly topical and exciting new knowledge of broad biological significance. The project will help establishing inter ....Regulation of autophagy dependent cell and tissue deletion. This project aims to elucidate novel mechanisms that regulate autophagy-depdendent cell death during animal development. It will combine the power of Drosophila genetics with multidisciplinary approaches, such as proteomics, bioinformatics and cell biology. Given the conserved nature of autophagy the oucomes will provide highly topical and exciting new knowledge of broad biological significance. The project will help establishing international collaborations, enhancing Australia’s competitiveness and reputation in an important area of research, and provide training of HDR students in skills across a range of areas. In the long-term the research findings may translate into improved agriculture, food production and human health outcomes.Read moreRead less
Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of ....Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of TRP channels. Preliminary data show that the first candidate, TRPV3, is activated in hypoxia, is hydroxylated by FIH, and hydroxylation mediates changes in activity. Ion channels are important for the physiological response to hypoxia, and this project aims to define a novel mechanism for this response, with relevance to mammalian physiology.Read moreRead less
Re-purposing shelved 'antibiotics' in the search for new herbicides. This project aims to identify target-specific herbicidal compounds that inhibit amino acid biosynthesis pathways to tackle herbicide resistance. This project expects to validate a novel herbicide discovery strategy by exploiting the similarity between bacterial and plant enzymes in these pathways to re-purpose failed 'antibiotics'. Expected outcomes include advances in our knowledge of the structure, function and inhibition of ....Re-purposing shelved 'antibiotics' in the search for new herbicides. This project aims to identify target-specific herbicidal compounds that inhibit amino acid biosynthesis pathways to tackle herbicide resistance. This project expects to validate a novel herbicide discovery strategy by exploiting the similarity between bacterial and plant enzymes in these pathways to re-purpose failed 'antibiotics'. Expected outcomes include advances in our knowledge of the structure, function and inhibition of novel herbicide targets, and the identification of compounds with herbicidal activity. This should lay the foundations for long-term benefits related to improving the quantity and quality of Australia’s crops to ensure our food security.Read moreRead less
Characterisation of vital carbohydrate synthases in pathogenic oomycetes. This project aims to understand the mechanisms that control cell wall stability in the fish pathogen, Saprolegnia parasitica. The biochemical properties and function of vital enzymes involved in cell wall biosynthesis will be determined using innovative approaches at the interface of biochemistry, microbiology, cell biology, and structural biology. Next generation ion mobility mass spectrometry will be used to solve challe ....Characterisation of vital carbohydrate synthases in pathogenic oomycetes. This project aims to understand the mechanisms that control cell wall stability in the fish pathogen, Saprolegnia parasitica. The biochemical properties and function of vital enzymes involved in cell wall biosynthesis will be determined using innovative approaches at the interface of biochemistry, microbiology, cell biology, and structural biology. Next generation ion mobility mass spectrometry will be used to solve challenging structural questions that cannot be tackled with conventional techniques. Expected outcomes include new knowledge on challenging membrane proteins that allows development of novel strategies for disease control in aquaculture. The data may also be applicable to crop protection from related plant pathogens.Read moreRead less
Unravelling cell wall polysaccharide biosynthesis in pathogenic zygomycetes. This project aims to define mechanisms that control cell wall composition and stability in Rhizopus oryzae, a zygomycete fungus responsible for life-threatening human infections. The biochemical properties and function of vital enzymes involved in a newly discovered cell wall polysaccharide biosynthetic pathway will be determined using innovative approaches at the interface of biochemistry, microbiology, cell biology an ....Unravelling cell wall polysaccharide biosynthesis in pathogenic zygomycetes. This project aims to define mechanisms that control cell wall composition and stability in Rhizopus oryzae, a zygomycete fungus responsible for life-threatening human infections. The biochemical properties and function of vital enzymes involved in a newly discovered cell wall polysaccharide biosynthetic pathway will be determined using innovative approaches at the interface of biochemistry, microbiology, cell biology and structural biology. Expected outcomes include new knowledge on the enzymes that synthesise major fucose-based carbohydrates, to guide the future development of novel strategies for antifungal therapies. The data will also be applicable to animal protection from related zygomycete pathogens.
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Three-dimensional structures, substrate specificities and catalytic mechanisms of polysaccharide synthases. Plant wall polysaccharides are extensively used for food and fibre, and are important dietary components in human nutrition. A precise knowledge of mechanisms used by plants to synthesize these polysaccharides is unavailable, but would reveal potential routes to manipulate their biosynthesis in important crop species. For example, the levels or structures of polysaccharides might be modif ....Three-dimensional structures, substrate specificities and catalytic mechanisms of polysaccharide synthases. Plant wall polysaccharides are extensively used for food and fibre, and are important dietary components in human nutrition. A precise knowledge of mechanisms used by plants to synthesize these polysaccharides is unavailable, but would reveal potential routes to manipulate their biosynthesis in important crop species. For example, the levels or structures of polysaccharides might be modified to improve their efficacy as anti-cancer agents in human diets, to enhance digestibility of animal stock feeds, or to synthesise pharmologically valuable compounds. Thus, economic, social and environmental benefits will flow to both producers and consumers. Read moreRead less