Investigation Of Biological Ion Channels: Theoretical Formulation, Computer Simulation And Experimental Verification
Funder
National Health and Medical Research Council
Funding Amount
$677,292.00
Summary
All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, undertanding their mechanisms at a molecular level is a fundamental problem in neurobiology. There are many different types of ion channels, each type fulfilling a different role. For the first time, a group of American scientists have determined the shape of one type of ion channels. Using this newly unveiled information, we propose to build a mathematical theory of ion channels. And then, making ....All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, undertanding their mechanisms at a molecular level is a fundamental problem in neurobiology. There are many different types of ion channels, each type fulfilling a different role. For the first time, a group of American scientists have determined the shape of one type of ion channels. Using this newly unveiled information, we propose to build a mathematical theory of ion channels. And then, making use of a powerful supercomputer, we propose to follow the motion of ions as they move through the channel, study how a channel can select only the correct type of ions to traverse it and determine how many ions a single channel is capable of processing per second. The predictions made by our theory and computer simulations will be checked experimentally. If the predictions and experimental findings do not agree, we will modify the theory and make new predictions.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775660
Funder
Australian Research Council
Funding Amount
$500,000.00
Summary
A National Biomedical Electron Paramagnetic Resonance and Molecular Imaging Centre. Multifrequency continuous wave and pulsed electron paramagnetic resonance spectroscopy and molecular imaging instrumentation will provide forefront technologies in identifying, characterising, quantifying, visualising and manipulating fundamental chemical and biologically relevant processes involving free radicals, metalloproteins and metal ions. This technology is crucial in validating these functional processes ....A National Biomedical Electron Paramagnetic Resonance and Molecular Imaging Centre. Multifrequency continuous wave and pulsed electron paramagnetic resonance spectroscopy and molecular imaging instrumentation will provide forefront technologies in identifying, characterising, quantifying, visualising and manipulating fundamental chemical and biologically relevant processes involving free radicals, metalloproteins and metal ions. This technology is crucial in validating these functional processes at the cellular and tissue level and for providing invaluable and unique biomedical information under physiological conditions. This synergistic and highly integrative approach will make available new techniques for identifying major disease mechanisms such as cardiovascular disease with a potential to improve and maintain health. Read moreRead less
Electric field induced surface attachment and detachment of proteins. Microarrays are revolutionising the diagnosis of disease by enabling large amounts of data on genetics and protein expression to be obtained from one sample. Biosensors for diseases and toxins rely on the same mechanism, namely attachment of biological macromolecules to a surface. We propose a new method for controlling the attachment by micromachining an electrode system to apply an electric field to chosen sites. Ultimately ....Electric field induced surface attachment and detachment of proteins. Microarrays are revolutionising the diagnosis of disease by enabling large amounts of data on genetics and protein expression to be obtained from one sample. Biosensors for diseases and toxins rely on the same mechanism, namely attachment of biological macromolecules to a surface. We propose a new method for controlling the attachment by micromachining an electrode system to apply an electric field to chosen sites. Ultimately microelectronic engineering methods will be used. This will give control over the attachment process with potential benefits of orienting attaching molecules, minimising non-specific attachment and enriching diagnostics by enabling interrogation of the force of attachment.Read moreRead less
Verification of a theoretical model of the dynamical genesis of brain electrical activity. The physiological basis for the rhythmic scalp electrical activity known as the alpha rhythm has remained elusive despite being first recorded over eighty years ago. However, one of the applicants (DTJL) has developed a novel theory of the electroencephalogram (EEG) that theoretically articulates the necessary physiological conditions required for the genesis of this activity that is subject to rigorous e ....Verification of a theoretical model of the dynamical genesis of brain electrical activity. The physiological basis for the rhythmic scalp electrical activity known as the alpha rhythm has remained elusive despite being first recorded over eighty years ago. However, one of the applicants (DTJL) has developed a novel theory of the electroencephalogram (EEG) that theoretically articulates the necessary physiological conditions required for the genesis of this activity that is subject to rigorous experimental test. Empirical verification of this theory will pave the way to elucidating the functional importance of large scale brain electrical activity in neural information processing as well as enabling the rational use of the EEG for drug design and diagnosis.Read moreRead less
Characterisation And Regulation Of Chloride Channels In Cardiac And Skeletal Sarcoplasmic Reticulum In Mammals
Funder
National Health and Medical Research Council
Funding Amount
$381,856.00
Summary
An understanding of the operation of ion channels in cell membranes is fundamental to our knowledge of the function of muscles under normal conditions and in pathological states that modify cell function, e.g. myotonia and cardiac failure. Ion channels control the flow of currents and the transport of substances which ultimately determine whether cells live or die, and hence whether cell pathologies are expressed as muscle failure, as when hypoxia causes tissue damage to the heart, or as severe ....An understanding of the operation of ion channels in cell membranes is fundamental to our knowledge of the function of muscles under normal conditions and in pathological states that modify cell function, e.g. myotonia and cardiac failure. Ion channels control the flow of currents and the transport of substances which ultimately determine whether cells live or die, and hence whether cell pathologies are expressed as muscle failure, as when hypoxia causes tissue damage to the heart, or as severe arrythmia or cardiac arrest. The objective is to understand channel involvement in the mechanisms underlying the function of cardiac and skeletal muscle. We believe that by mimicking the factors that occur in pathological conditions we can understand how ion channels are altered and controlled, and find ways of reversing harmful alterations, thereby reversing cell damage and failure of vital muscle function.Drugs will be used to modify the 'gating' of the channels. By comparing the effects of different drugs, we hope to determine the important features of the mechanisms that control the gating of the channels, making them more or less sensitive to different influences, especially those that occur in pathological states. The study has great application to the study of other pathologies, e.g. cystic fibrosis, severe diarrhoea, paralysis and chronic fatigue. The pharmacological emphasis offers the fundamental science needed to design novel and specific drugs to combat the many serious pathologies related to ion channel effects. Aside from its importance to basic science and to immediate issues of health, the study offers considerable economic gains, both through improved public health and through development of pharmaceuticals.Read moreRead less
Creation of functional surfaces for biodevices and aerospace applications. Polymers are poised to become the materials of choice for a host of applications because of their lightness, strength, ease of forming and biocompatibility. The major challenge lies in optimising their surfaces for each application. For biodevices in particular, the surfaces must support a range of complex and specific interactions. This project will create new polymer surface modifications through innovations in plasma s ....Creation of functional surfaces for biodevices and aerospace applications. Polymers are poised to become the materials of choice for a host of applications because of their lightness, strength, ease of forming and biocompatibility. The major challenge lies in optimising their surfaces for each application. For biodevices in particular, the surfaces must support a range of complex and specific interactions. This project will create new polymer surface modifications through innovations in plasma science and technology. The outcomes will be new surfaces for diagnostic arrays in medicine, biosensors and durable polymer surfaces for low earth orbit.Read moreRead less
Understanding aerobic respiration: Models for the catalytic centre in proton-pumping heme-copper oxidases. This project tackles ?head on? a key challenge in contemporary biological inorganic chemistry, understanding how at the atomic level aerobic life uses oxygen. All life we see is aerobic, and thus the conceptual advances from this research will progress understanding of our world and ourselves? an important cultural goal. Advancing knowledge of such fundamental processes sits firmly in the a ....Understanding aerobic respiration: Models for the catalytic centre in proton-pumping heme-copper oxidases. This project tackles ?head on? a key challenge in contemporary biological inorganic chemistry, understanding how at the atomic level aerobic life uses oxygen. All life we see is aerobic, and thus the conceptual advances from this research will progress understanding of our world and ourselves? an important cultural goal. Advancing knowledge of such fundamental processes sits firmly in the area of the Research Priority Goal: Breakthrough Science. Postgraduate research students will be trained in sophisticated state-of-the-art theoretical and synthetic chemical methodologies. The project will enhance Australia's research capability in biological (inorganic) chemistry and promote Australia's standing in the International research community.Read moreRead less
Biomolecular activity modulated by interaction with nanostructures. Nanotechnological methods are able to reliably fabricate artificial nanostructures with dimensions similar to those of large biomolecules (a few to tens of nanometers). This study focuses on the interaction of artificial nanostructures with biomolecules such as proteins and DNA, and will enable scientists to better understand biomolecular recognition and binding events, which are central to all biological processes. The underst ....Biomolecular activity modulated by interaction with nanostructures. Nanotechnological methods are able to reliably fabricate artificial nanostructures with dimensions similar to those of large biomolecules (a few to tens of nanometers). This study focuses on the interaction of artificial nanostructures with biomolecules such as proteins and DNA, and will enable scientists to better understand biomolecular recognition and binding events, which are central to all biological processes. The understanding gained can then be used to design biomimetic surfaces for use in health monitoring and medical diagnostic devices with improved sensitivity, robustness and portability, thereby providing significant benefits to the health sector.Read moreRead less
A rational approach to a high-resolution structure of the multidrug transporter EmrE. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. Multidrug transporters are membrane proteins responsible for antibiotic resistance in humans. A high-resolution structure of a multidrug resistance protein, together with comprehensive biochemical characterization, w ....A rational approach to a high-resolution structure of the multidrug transporter EmrE. Membrane proteins form only 0.3% of the available protein structures in the protein data bank (PDB), yet 30% of the proteins in the human genome and 50% of human drug targets are membrane proteins. Multidrug transporters are membrane proteins responsible for antibiotic resistance in humans. A high-resolution structure of a multidrug resistance protein, together with comprehensive biochemical characterization, would enable a detailed understanding of how these protein functions. Potentially it could also aid in the development of specific inhibitors that would prevent EmrE (and perhaps other similar proteins) from carry out its harmful mission. Read moreRead less