New Insights into the Structure and Function of Pyruvate Carboxylase. Pyruvate carboxylase plays an essential roles in insulin secretion by pancreatic islets and in normal brain function, but excess expression of this enzyme in liver and adipose tissue is associated with diabetes and obesity.
Understanding the function of each structural feature in the reaction mechanism of an enzyme is essential to designing safe and effective pharmaceuticals that are required to modulate its activity.
Th ....New Insights into the Structure and Function of Pyruvate Carboxylase. Pyruvate carboxylase plays an essential roles in insulin secretion by pancreatic islets and in normal brain function, but excess expression of this enzyme in liver and adipose tissue is associated with diabetes and obesity.
Understanding the function of each structural feature in the reaction mechanism of an enzyme is essential to designing safe and effective pharmaceuticals that are required to modulate its activity.
This project, which will use cutting edge techniques in an experimental model, seeks to characterise this important enzyme's function so that better treatments can be developed in future for diabetes and obesity.
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A genomic approach to the mechanism of meiotic recombination in Neurospora. Recombination shuffles DNA sequences between homologous chromosomes during the reduction division in the life cycle of higher organisms. Along with mutation, it is a key process in evolution. Understanding of the molecular processes involved in recombination is largely based on yeast, which is intolerant of significant levels of sequence mismatch, limiting the resolution of analyses of normal recombination events. We hav ....A genomic approach to the mechanism of meiotic recombination in Neurospora. Recombination shuffles DNA sequences between homologous chromosomes during the reduction division in the life cycle of higher organisms. Along with mutation, it is a key process in evolution. Understanding of the molecular processes involved in recombination is largely based on yeast, which is intolerant of significant levels of sequence mismatch, limiting the resolution of analyses of normal recombination events. We have shown that Neurospora, like other less tractable multicellular eukaryotes, is tolerant of sequence mismatch, allowing high resolution analysis of individual recombination events. This project will build on fundamental advances we have already made in understanding how recombination occurs.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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Defining New Building Blocks for the Construction of Artificial Genetic Circuits. By characterising the components of a natural genetic switch, we will make available a set of well defined genetic building blocks for construction of rationally designed biological circuits. The ability to build such circuits would have significant economic benefit in areas such as metabolic engineering, to improve the efficiency of production of natural compounds from micro-organisms, and in biomedicine, for the ....Defining New Building Blocks for the Construction of Artificial Genetic Circuits. By characterising the components of a natural genetic switch, we will make available a set of well defined genetic building blocks for construction of rationally designed biological circuits. The ability to build such circuits would have significant economic benefit in areas such as metabolic engineering, to improve the efficiency of production of natural compounds from micro-organisms, and in biomedicine, for the controlled release of therapeutic compounds. The involvement of Honours and Ph.D students in this project will expose the next generation of Australian scientists to this emerging discipline. International collaboration leading to publications in high impact scientific journals will enhance Australia's scientific reputation.Read moreRead less
Solving the Mysteries of Monotreme Chromosomes. The peculiar chromosomes of Australia's platypus and echidna have been debated for more than 30 years. Classical cytology cannot resolve the puzzling sex chromosome system, or to sort out the bizarre translocation chain (unique in vertebrates) and deduce how it segregates to make viable zyotes. I will microdissect individual chromosomes, and use DNA ?paints? from them (and gene probes isolated by them) to detect homologies between unpaired chromoso ....Solving the Mysteries of Monotreme Chromosomes. The peculiar chromosomes of Australia's platypus and echidna have been debated for more than 30 years. Classical cytology cannot resolve the puzzling sex chromosome system, or to sort out the bizarre translocation chain (unique in vertebrates) and deduce how it segregates to make viable zyotes. I will microdissect individual chromosomes, and use DNA ?paints? from them (and gene probes isolated by them) to detect homologies between unpaired chromosomes at mitosis, meiosis and in sperm. I will use immunohistochemistry to clarify chromosome pairing and recombination at meiosis. This will answer some important general questions about chromosome behaviour and sex chromosome evolution.
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Genetic control of floral architecture. Different flowers have different designs, and so the design must ultimately be controlled by genes. We have identified a gene that keeps sepals separate, and promotes the initiation of petals. We think it does this by a novel growth suppression mechanism, and will now deduce its molecular and cellular basis. This will help maintain Australia's strength in fundamental plant biology. Also, by understanding how sepals and petals arise in a model laboratory sp ....Genetic control of floral architecture. Different flowers have different designs, and so the design must ultimately be controlled by genes. We have identified a gene that keeps sepals separate, and promotes the initiation of petals. We think it does this by a novel growth suppression mechanism, and will now deduce its molecular and cellular basis. This will help maintain Australia's strength in fundamental plant biology. Also, by understanding how sepals and petals arise in a model laboratory species, we can generalise for many species, including economic plants. Thus it may be possible to make designer crops through targeted genetic changes to their floral structure.Read moreRead less
Control of plant organ development by the PETAL LOSS gene of Arabidopsis. We have discovered a new gene in the model laboratory plant Arabidopsis thaliana that is involved in sepal and petal development. It encodes a transcription factor that apparently acts by repressing growth in the inter-sepal zone of flowers where petals arise. We now aim to determine how this growth suppression occurs, and whether it extends to leaves where the gene is also expressed. Control of the initiation and sculptur ....Control of plant organ development by the PETAL LOSS gene of Arabidopsis. We have discovered a new gene in the model laboratory plant Arabidopsis thaliana that is involved in sepal and petal development. It encodes a transcription factor that apparently acts by repressing growth in the inter-sepal zone of flowers where petals arise. We now aim to determine how this growth suppression occurs, and whether it extends to leaves where the gene is also expressed. Control of the initiation and sculpturing of plant organs by site-specific inhibition of growth is a newly discovered mechanism that may be useful in manipulating plant architecture.Read moreRead less
Understanding how auxin and dorsoventral patterning are coordinated in plants. This study will help reveal for the first time how the outgrowth of leaves, flowers and floral organs is coordinated by tissue patterning genes and the plant growth hormone auxin. All plants grow in this way, and our findings, made using a model laboratory plant, will be applicable to crop species as well. Thus we will both expand our core knowledge of how multicellular organisms are constructed, and also generate pos ....Understanding how auxin and dorsoventral patterning are coordinated in plants. This study will help reveal for the first time how the outgrowth of leaves, flowers and floral organs is coordinated by tissue patterning genes and the plant growth hormone auxin. All plants grow in this way, and our findings, made using a model laboratory plant, will be applicable to crop species as well. Thus we will both expand our core knowledge of how multicellular organisms are constructed, and also generate possibilities for modifying the patterns of leaf and flower development in agricultural and horticultural species. Crops with larger leaves, or flowers of different structure, may result.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
Gating and permeation in ClC channels. Chloride ion channels are essential proteins in all living cells but, compared to other channels, little is known of their structure or how this defines and controls chloride transport. We will produce both normal and structurally modified (mutant and known to cause disease) chloride channels in cultured cells by genetic engineering so that we can analyse channel function using a combination of electrophysiological and chemical methods. We expect to learn ....Gating and permeation in ClC channels. Chloride ion channels are essential proteins in all living cells but, compared to other channels, little is known of their structure or how this defines and controls chloride transport. We will produce both normal and structurally modified (mutant and known to cause disease) chloride channels in cultured cells by genetic engineering so that we can analyse channel function using a combination of electrophysiological and chemical methods. We expect to learn which channel parts are fundamental and how subtle changes in structure can alter the opening and closing of these channels and the way that chloride passes through them.Read moreRead less