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
TeraHertz Cell Cluster Imaging. With this program, Australia will benefit from the interaction between physics, engineering, biology and medicine to develop a new TeraHertz imaging system. The project will identify the factors that contribute to TeraHertz contrast in soft tissue cell cultures, thereby developing a non-invasive imaging system to show contrast between diseased and healthy cells. This is a fundamental step towards a system for diagnosing disease states of skin cells, for example, t ....TeraHertz Cell Cluster Imaging. With this program, Australia will benefit from the interaction between physics, engineering, biology and medicine to develop a new TeraHertz imaging system. The project will identify the factors that contribute to TeraHertz contrast in soft tissue cell cultures, thereby developing a non-invasive imaging system to show contrast between diseased and healthy cells. This is a fundamental step towards a system for diagnosing disease states of skin cells, for example, the early detection of melanoma. Ultimately, Australia will benefit from a new technology, and new diagnostic biomedical techniques, for rapid, non-invasive and reliable skin cancer diagnosis.Read moreRead less
Correlation between surface force and morphology of self-assembled monolayer. As a most potential solid support for biological molecules without denaturing their functions, gold thiol self-assembled monolayers (SAMs) have been studied extensively for surface fabrication. In this project we will prepare functional monolayers using newly synthesized thiol derivatives, evaluate correlation between surface force and surface morphology of the SAMs using the surface forces apparatus, and optimize the ....Correlation between surface force and morphology of self-assembled monolayer. As a most potential solid support for biological molecules without denaturing their functions, gold thiol self-assembled monolayers (SAMs) have been studied extensively for surface fabrication. In this project we will prepare functional monolayers using newly synthesized thiol derivatives, evaluate correlation between surface force and surface morphology of the SAMs using the surface forces apparatus, and optimize the condition to fabricate biological devices such as immune sensors.Read moreRead less
Breaking The Wavelength Barrier: Near-Field T-ray Imaging. Australia will benefit from the interaction between engineering, physics, and biology to develop a new T-ray imaging system that will ultimately be able to probe microstructures, biological single cells or even neurons. The project will exploit a powerful new electrooptical technique for obtaining chemical 'fingerprints' at the cellular level. This breakthrough will be a fundamental step towards a system for probing disease states of sin ....Breaking The Wavelength Barrier: Near-Field T-ray Imaging. Australia will benefit from the interaction between engineering, physics, and biology to develop a new T-ray imaging system that will ultimately be able to probe microstructures, biological single cells or even neurons. The project will exploit a powerful new electrooptical technique for obtaining chemical 'fingerprints' at the cellular level. This breakthrough will be a fundamental step towards a system for probing disease states of single cells and will open up new lines of scientific enquiry. Ultimately, Australia will benefit from a new technology and new diagnostic biomedical techniques. This is potentially an enabling technology for future customised medicine, where rapid biochip sensing becomes foreseeable.Read moreRead less
Towards a miniaturised on-chip terahertz biosensing system. Terahertz (or T-ray) radiation is highly sensitive to minute changes in the molecular structure of many substances. Furthermore most packing materials are transparent to this new form of radiation. This implies enormous potential for T-rays in a range of applications from quality control via non-invasive contact-less chemical fingerprinting through to safety and security applications. A detailed study of the molecular vibrations that gi ....Towards a miniaturised on-chip terahertz biosensing system. Terahertz (or T-ray) radiation is highly sensitive to minute changes in the molecular structure of many substances. Furthermore most packing materials are transparent to this new form of radiation. This implies enormous potential for T-rays in a range of applications from quality control via non-invasive contact-less chemical fingerprinting through to safety and security applications. A detailed study of the molecular vibrations that give rise to these fingerprints will help chemists and biologists to learn more about the underlying molecular binding forces, impacting on wide applications for safe non-invasive sensing in the medical, security, chemical and food industries.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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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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Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0560862
Funder
Australian Research Council
Funding Amount
$546,700.00
Summary
South Australian Facility for Advanced Molecular Imaging. The aim of this project is to establish the South Australian Facility for Advanced Molecular Imaging. The Facility builds on existing expertise and cooperation between the collaborating institutions to expand our capability in advanced analytical confocal microscopy of a wide range of materials from living cells to artificial surfaces. New state-of-the-art microscopes will allow the direct quantitative analysis of molecular interactions w ....South Australian Facility for Advanced Molecular Imaging. The aim of this project is to establish the South Australian Facility for Advanced Molecular Imaging. The Facility builds on existing expertise and cooperation between the collaborating institutions to expand our capability in advanced analytical confocal microscopy of a wide range of materials from living cells to artificial surfaces. New state-of-the-art microscopes will allow the direct quantitative analysis of molecular interactions with high temporal and spatial resolutions. This will advance: understanding the regulation of cellular signalling, gene expression and growth in normal and pathological conditions; development of biosensor technology; and the application of new biomaterials in medicine and industry.Read moreRead less