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
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
Small is beautiful: Did gene-rich regions of mammal chromosomes evolve from microchromosomes? Most birds and reptile genomes feature many tiny microchromosomes. These are not junk, as previously thought, but contain most of the genes. Mammals lack microchromosomes, but contain gene-rich regions with similar attributes. We suggest that microchromosomes originated by genome duplication, and evolved into the gene-rich regions of mammalian chromosomes. We will test this hypothesis by comparing seque ....Small is beautiful: Did gene-rich regions of mammal chromosomes evolve from microchromosomes? Most birds and reptile genomes feature many tiny microchromosomes. These are not junk, as previously thought, but contain most of the genes. Mammals lack microchromosomes, but contain gene-rich regions with similar attributes. We suggest that microchromosomes originated by genome duplication, and evolved into the gene-rich regions of mammalian chromosomes. We will test this hypothesis by comparing sequences and genes in microchromosomes of birds, reptiles and monotremes. This will clarify the origin and evolution of the ?microgenome?, establish its suitability as a model for vertebrate genome organisation, and demonstrate whether microchromosomes are the ancestors of the gene-rich regions of mammalian chromosomes.Read moreRead less
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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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775503
Funder
Australian Research Council
Funding Amount
$255,000.00
Summary
Robotics for plant genomics: Increasing throughput in plant genetic analyses. Plant genomics has direct benefit to crop improvement, especially as focussed in the applicants' laboratories. Thus, the Australian agri-food sector will benefit substantially from the acceleration in plant functional genomics that will arise from the installation of the robotics equipment described in the current application, by both underpinning more applied research and also being used directly in crop improvement p ....Robotics for plant genomics: Increasing throughput in plant genetic analyses. Plant genomics has direct benefit to crop improvement, especially as focussed in the applicants' laboratories. Thus, the Australian agri-food sector will benefit substantially from the acceleration in plant functional genomics that will arise from the installation of the robotics equipment described in the current application, by both underpinning more applied research and also being used directly in crop improvement programs such as are based at the Waite Campus. The outputs will include crops with increased tolerance to biotic and abiotic stresses, a reduced dependence on chemical inputs such as fertilisers and improved food quality, with consequent benefits to the environment and human health and nutrition.Read moreRead less
Endosymbiotic DNA transfer. Interorganellar DNA movement is a major force in evolution. In higher organisms, the prokaryotic ancestors of mitochondria and chloroplasts donated many genes to the nucleus. Plants have unique potential in studies of the mechanisms that have driven genome evolution. We established experimentally that DNA moves from the chloroplast to the nucleus at high frequency and this provided us with a world lead in this scientifically new area. The relocated genes contribute to ....Endosymbiotic DNA transfer. Interorganellar DNA movement is a major force in evolution. In higher organisms, the prokaryotic ancestors of mitochondria and chloroplasts donated many genes to the nucleus. Plants have unique potential in studies of the mechanisms that have driven genome evolution. We established experimentally that DNA moves from the chloroplast to the nucleus at high frequency and this provided us with a world lead in this scientifically new area. The relocated genes contribute to the number and diversity of genes and gene function. Genetically manipulated (GM) crops use the chloroplast compartment to make high levels of protein, necessitating a full understanding of how transgenes behave within the cellular and the external environment.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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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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Trafficking of DNA between chloroplast and nucleus in higher plants. Reliably high levels of diverse proteins can be produced in plant chloroplasts. Environmental risks are considered low for chloroplast genes because they are not transmitted by pollen. However, we recently discovered that DNA escapes from the tobacco chloroplast to the nucleus with unexpectedly high frequency. The associated environmental risks require immediate investigation. This project will determine the fate of chloroplast ....Trafficking of DNA between chloroplast and nucleus in higher plants. Reliably high levels of diverse proteins can be produced in plant chloroplasts. Environmental risks are considered low for chloroplast genes because they are not transmitted by pollen. However, we recently discovered that DNA escapes from the tobacco chloroplast to the nucleus with unexpectedly high frequency. The associated environmental risks require immediate investigation. This project will determine the fate of chloroplast DNA that has moved to the nuclear genome and gain insight into the evolutionary and environmental consequences of chloroplast DNA escape. The ubiquity of DNA escape also will be studied in an edible crop with a small genome, tomato.Read moreRead less
Analysis of interorganellar transposition of DNA. The movement of DNA between organelles is a major driving force in the eukaryotic evolution. In yeast about 75% of all nuclear genes may derive from protomitochondria. Though DNA transfer per se continues in all higher cells, including mammals, in most species the functional transfer of genes has stopped. It continues at a high rate in plants, giving them unique potential in evolutionary studies of the genome. We established experimentally that D ....Analysis of interorganellar transposition of DNA. The movement of DNA between organelles is a major driving force in the eukaryotic evolution. In yeast about 75% of all nuclear genes may derive from protomitochondria. Though DNA transfer per se continues in all higher cells, including mammals, in most species the functional transfer of genes has stopped. It continues at a high rate in plants, giving them unique potential in evolutionary studies of the genome. We established experimentally that DNA moves frequently from the plastid (chloroplast) to the nucleus. We now aim to measure the frequency of DNA transposition from the plastid to the mitochondrion. If transposition is sufficiently frequent, the approach can be used to transformation the mitochondrial genome.Read moreRead less