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
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: LE0668241
Funder
Australian Research Council
Funding Amount
$824,610.00
Summary
A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflamma ....A Facility for High-Throughput, Functional Gene Discovery Using Arrayed Retroviral Expression Cloning. The proposed facility will represent world-leading technology in functional genomics and provide Australian scientists with unique opportunities to identify genes involved in a broad range of biological processes. This will contribute to fundamental knowledge in mammalian biology, and equally importantly, is likely to identify genes involved in important health problems such as cancer, inflammatory disease, brain damage and diabetes. Such genes may in turn constitute targets against which new therapies may be developed. This endeavour will contribute to national research priorities in both the health and scientific/technological development arenas.Read moreRead less
A shipload of consequences: studying the impact of Old World diseases on native South American populations via ancient DNA. This pioneering project will give the first real-time picture of the genetic changes induced by epidemics in human populations. This will reveal important new information about the likely impact of future epidemics on the genetic diversity of the immune system in modern human populations and will be of substantial use in building epidemiological models. By proposing to comb ....A shipload of consequences: studying the impact of Old World diseases on native South American populations via ancient DNA. This pioneering project will give the first real-time picture of the genetic changes induced by epidemics in human populations. This will reveal important new information about the likely impact of future epidemics on the genetic diversity of the immune system in modern human populations and will be of substantial use in building epidemiological models. By proposing to combine state-of-the-art science with global problems of humanity, we will address Australia's interests in expanding scientific expertise beyond its borders and place Australia at the leading edge of disease impact studies.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0453839
Funder
Australian Research Council
Funding Amount
$386,892.00
Summary
Adelaide Core Laser Capture Microscopy Facility. Laser Capture Microscopy represents a powerful and essential tool in many aspects of modern cell and molecular biology. Although the applications for these machines are very broad, overall the technology can be viewed as allowing collection of rare cells (or objects as small as bacteria and organelles) from complex tissues and cells. This proposal concerns infrastructure funding to obtain a state-of-the-art core Laser Capture Microscope facility ....Adelaide Core Laser Capture Microscopy Facility. Laser Capture Microscopy represents a powerful and essential tool in many aspects of modern cell and molecular biology. Although the applications for these machines are very broad, overall the technology can be viewed as allowing collection of rare cells (or objects as small as bacteria and organelles) from complex tissues and cells. This proposal concerns infrastructure funding to obtain a state-of-the-art core Laser Capture Microscope facility in Adelaide that will significantly enhance scientific progress in a diverse range of areas including functional genomics of animal, plant and prokaryotic cells.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0989374
Funder
Australian Research Council
Funding Amount
$550,000.00
Summary
South Australian High-Resolution and Ion-Mobility Mass Spectrometry Facility. The analytical facility will enhance (i) fundamental research to understand the mechanisms of the reactions of charged species with neutral molecules, and (ii) the provision of structural information, including the precise atomic composition of any molecule, small or large. Research supported by this facility includes (a)nanotechnology, including supramolecular chemistry, (b) bioscience: cancer research, neurodegenera ....South Australian High-Resolution and Ion-Mobility Mass Spectrometry Facility. The analytical facility will enhance (i) fundamental research to understand the mechanisms of the reactions of charged species with neutral molecules, and (ii) the provision of structural information, including the precise atomic composition of any molecule, small or large. Research supported by this facility includes (a)nanotechnology, including supramolecular chemistry, (b) bioscience: cancer research, neurodegenerate diseases (e.g. Parkinson's disease) osteoarthritis, inflammation, cardiac diseases and synthetic approaches to anticancer and other drugs.Read moreRead less
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
Special Research Initiatives - Grant ID: SR0354622
Funder
Australian Research Council
Funding Amount
$20,000.00
Summary
Genes and Environment in Development. Interactions between the early environment and the genetic regulatory program of the early embryo have major consequences for the development of individuals. The aim of this Network is to harness the resources of leading researchers from the previously distinct disciplines of developmental biology and developmental physiology to better understand developmental regulatory networks and how environmental factors impinge on them. The formation of such a Network ....Genes and Environment in Development. Interactions between the early environment and the genetic regulatory program of the early embryo have major consequences for the development of individuals. The aim of this Network is to harness the resources of leading researchers from the previously distinct disciplines of developmental biology and developmental physiology to better understand developmental regulatory networks and how environmental factors impinge on them. The formation of such a Network is unique, timely and strategic in that it will generate new insights into the mechanisms by which events in early life determine the risk of adverse outcomes in perinatal and adult life.Read moreRead less
ARC/NHMRC Research Network in Genes and Environment in Development. Interactions between the early environment and the genetic regulatory program of the developing organism have major consequences for the lifetime health of individuals. The primary objective of the Network in Genes and Environment in Development is to harness the resources of leading researchers from the currently distinct disciplines of developmental biology and developmental physiology to define key developmental regulatory ne ....ARC/NHMRC Research Network in Genes and Environment in Development. Interactions between the early environment and the genetic regulatory program of the developing organism have major consequences for the lifetime health of individuals. The primary objective of the Network in Genes and Environment in Development is to harness the resources of leading researchers from the currently distinct disciplines of developmental biology and developmental physiology to define key developmental regulatory networks and to address how environmental factors impinge on these regulatory networks. The formation of this National Research Network is unique, timely and strategic. It will generate new insights into the mechanisms by which events in early life determine the risk of adverse outcomes in perinatal and adult life.Read moreRead less