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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561030
Funder
Australian Research Council
Funding Amount
$441,100.00
Summary
Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiative ....Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiatives in developmental and cellular biology. This large-scale, high-resolution expression profiling infrastructure is required to maintain international competitiveness and will dramatically improve our gene discovery, functional assessment and understanding of vertebrate development.Read moreRead less
Proteomic analysis of central nervous system inflammation in multiple sclerosis. This project aims to identify new therapeutic targets and diagnostics for Multiple Sclerosis (MS) the most common neurological disease in young adults. The estimated economic burden of this disease in Australia is around $2 billion per annum. There is also a large social cost to take into account. In spite of a great deal of research, current therapies are limited. We expect that this this research will: lead to n ....Proteomic analysis of central nervous system inflammation in multiple sclerosis. This project aims to identify new therapeutic targets and diagnostics for Multiple Sclerosis (MS) the most common neurological disease in young adults. The estimated economic burden of this disease in Australia is around $2 billion per annum. There is also a large social cost to take into account. In spite of a great deal of research, current therapies are limited. We expect that this this research will: lead to new therapies and better diagnostics, which will reduce the financial and human cost of this disease; generate IP with subsequent economic benefits and; expand proteomics technologies which will have flow on effects including economic benefits and benefits to a wide range of basic research. Read moreRead less
Communication and information storage mechanisms in complex dynamical brain networks. Recordings of electrical activity in the brain often cycle repetitively. The aim of this research is to explain how these brain rhythms assist the brain to coordinate simultaneous activity in several regions. Australian socioeconomic benefits include: (i) contributions to the knowledge base of theoretical neuroscience, enhancing Australia's reputation for cutting-edge research; (ii) strengthening of internation ....Communication and information storage mechanisms in complex dynamical brain networks. Recordings of electrical activity in the brain often cycle repetitively. The aim of this research is to explain how these brain rhythms assist the brain to coordinate simultaneous activity in several regions. Australian socioeconomic benefits include: (i) contributions to the knowledge base of theoretical neuroscience, enhancing Australia's reputation for cutting-edge research; (ii) strengthening of international collaborations with Europe and Japan; (iii) outcomes will ultimately impact on improved medical bionics and future interfaces between brain activity and machines or computers; and (iv) commercialization and technology transfer opportunities, via the transfer of results to biologically inspired engineering.Read moreRead less
The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu pr ....The role of the neuronal Hu proteins in the regulation of the BMP signalling pathway. We aim to understand the critical decision of a neural progenitor to commit to becoming a neuron. The BMP signalling pathway is central in this decision. Neural progenitors appear to become insensitive to BMP signals, and this lack of signalling leads to neuronal differentiation. We hypothesise that neuronal identity is regulated by an unusual genetic switch- the translational regulation by the neuronal Hu proteins of two proteins in the BMP pathway. Verification of a post-transcriptional regulatory mechanism for cell fate determination would be a major discovery, and may prompt investigation of how to harness the neuron-inducing function of the Hu proteins to address the therapeutic need for new neurons in neurologic diseases.Read moreRead less
Many Ys in monotremes: multiple sex chromosomes and sex determination in platypus and echidna. Platypus and Echidna are Australian icons, even featuring on our coins. Their unusual biology and ancient relationship to humans make them unique for understanding the mammalian genome, as demonstrated by our recent discovery of ten sex chromosomes in platypus that link mammal and bird sex. Still little is known about their genome, embryo development and how sex is determined. We will identify new gene ....Many Ys in monotremes: multiple sex chromosomes and sex determination in platypus and echidna. Platypus and Echidna are Australian icons, even featuring on our coins. Their unusual biology and ancient relationship to humans make them unique for understanding the mammalian genome, as demonstrated by our recent discovery of ten sex chromosomes in platypus that link mammal and bird sex. Still little is known about their genome, embryo development and how sex is determined. We will identify new genes on all ten sex chromosomes and investigate how they determine sex. The set up of an Australian Monotreme Resource Centre will be crucial for this research and attract worldwide high profile collaborations. We will answer important general questions in monotreme biology and contribute to our understanding of sexual abnormalities in humans.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100010
Funder
Australian Research Council
Funding Amount
$720,000.00
Summary
A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the ....A 5-D Correlative Imaging Platform: Combining the strengths of light and electron microscopy. This will be Australia's first dedicated five-dimensional multiphoton-microscopy platform, allowing observation of dynamic structures across different length and time scales under controlled temperatures, followed by high-resolution electron microscopy studies on the same samples. This platform will provide a unique characterisation tool to Australia's top-flight investigators, and so contribute to the nation's research priorities. It will enable: fundamental studies of cancer, neural diseases and immune disorders; the development of frontier technologies, such as smart nanomaterials, biosensors and targeted drug delivery; and applied research to help plants and soils adapt to climate variability, and to increase sustainable use of water.Read moreRead less
The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and ....The basis of recognition and disposal of dysfunctional proteins by clusterin. When proteins become damaged they can precipitate. A blood protein called clusterin prevents precipitation of damaged proteins. Clusterin does this by forming complexes with the damaged proteins. Clusterin is the first blood protein known to do this. We will discover which parts of clusterin are responsible for this activity. We will also discover whether cells can take up and dispose of the complexes of clusterin and damaged proteins. This work is important because some diseases (eg, Alzheimers disease) involve the toxic effects of abnormal protein precipitation. Understanding how clusterin works may help in developing better treatments for these diseases.Read moreRead less
Structural and Functional Aspects of the Allosteric Regulation of Pyruvate Carboxylase by Acyl-CoA Compounds. Pyruvate carboxylase occupies a central location in intermediary metabolism catalysing the formation of oxaloacetate, a key component of the Krebs' tricarboxylic acid cycle especially in its synthetic modes in gluconeogenesis, lipogenesis and in the synthesis of neurotransmitters.
This project aims: (i) To produce crystals of pyruvate carboxylase for determining its structure by X-ra ....Structural and Functional Aspects of the Allosteric Regulation of Pyruvate Carboxylase by Acyl-CoA Compounds. Pyruvate carboxylase occupies a central location in intermediary metabolism catalysing the formation of oxaloacetate, a key component of the Krebs' tricarboxylic acid cycle especially in its synthetic modes in gluconeogenesis, lipogenesis and in the synthesis of neurotransmitters.
This project aims: (i) To produce crystals of pyruvate carboxylase for determining its structure by X-ray diffraction; (ii) To use affinity-labelling to determine the amino acid residues in the binding site of the enzyme's allosteric activator, acetyl-CoA; (iii) To construct chimeric enzymes from different species to define regions of the enzyme which affect its responses to its important allosteric activator, acetyl-CoA.
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Interactions of Insulin-like Growth Factors and their Binding Proteins with Vitronectin: a structural basis for antagonist design and development. Tissue Therapies Ltd has shown that a patented combination of three biosynthetic molecules, VitroGroR, can promote tissue repair effectively. This project will use biophysical and biochemical techniques to investigate precisely how these molecules interact, and hence provide a rational basis for future developments and improvements of this exciting n ....Interactions of Insulin-like Growth Factors and their Binding Proteins with Vitronectin: a structural basis for antagonist design and development. Tissue Therapies Ltd has shown that a patented combination of three biosynthetic molecules, VitroGroR, can promote tissue repair effectively. This project will use biophysical and biochemical techniques to investigate precisely how these molecules interact, and hence provide a rational basis for future developments and improvements of this exciting new therapeutic strategy.
Conversely, this information would also facilitate the development of antagonists to VitroGroR complexes would provide novel opportunities to treat diseases such as cancer and atherosclerosis that involve excessive production of its component molecules.Read moreRead less