Mapping Protein Contacts and Conformational Changes in Macromolecular Assemblies. We now have a great deal of information about the structures of proteins that interact to do much of the chemistry that governs the lives of cells and organisms, but are just beginning to understand how proteins communicate with each other in the large, dynamic molecular machines that carry out many cellular functions. Australia has invested in expensive instrumentation that can be used in conjunction with new labo ....Mapping Protein Contacts and Conformational Changes in Macromolecular Assemblies. We now have a great deal of information about the structures of proteins that interact to do much of the chemistry that governs the lives of cells and organisms, but are just beginning to understand how proteins communicate with each other in the large, dynamic molecular machines that carry out many cellular functions. Australia has invested in expensive instrumentation that can be used in conjunction with new laboratory methods to develop better understanding of how these machines work, and how they malfunction in disease. This project will bring together four scientists with a unique combination of expertise and novel technologies to develop understanding of changes in structure of a large protein complex in different functional states.Read moreRead less
High Resolution EPR Spectroscopy - A Tool for Determining Electronic and Geometric Structure of Metalloenzymes. High resolution orientation selective pulsed EPR and END(T)OR in conjunction with computer simulation (XSophe) and computational chemistry will allow the determination of the electronic and geometric structure (distance and orientation of nuclei surrounding the metal ion(s)) of multiple redox centres in DMSOR, DorC and DMSDH to be determined. In addition pulsed ELDOR in conjunction wi ....High Resolution EPR Spectroscopy - A Tool for Determining Electronic and Geometric Structure of Metalloenzymes. High resolution orientation selective pulsed EPR and END(T)OR in conjunction with computer simulation (XSophe) and computational chemistry will allow the determination of the electronic and geometric structure (distance and orientation of nuclei surrounding the metal ion(s)) of multiple redox centres in DMSOR, DorC and DMSDH to be determined. In addition pulsed ELDOR in conjunction with molecular modelling will enable the mapping (distance and orientation) of redox centres in complex multicentered metalloproteins (DMSDH and DorC) and in protein-protein complexes (DMSOR-DorC) providing information on the pathway of electron transfer and hence the role of the pyranopterins.Read moreRead less
Quantitative dynamics of functional magnetic resonance imaging. By modeling and verifying the dynamics of brain activity and blood flow that underlie functional magnetic resonance imaging (fMRI), this project will yield improved scientific outcomes and imaging sensitivity. The new data analysis techniques and technologies that result will yield potentially patentable intellectual property, and will increase the standing of Australia in this rapidly developing field, including via links being bu ....Quantitative dynamics of functional magnetic resonance imaging. By modeling and verifying the dynamics of brain activity and blood flow that underlie functional magnetic resonance imaging (fMRI), this project will yield improved scientific outcomes and imaging sensitivity. The new data analysis techniques and technologies that result will yield potentially patentable intellectual property, and will increase the standing of Australia in this rapidly developing field, including via links being built to leading international workers. The National Research Priority Goals of Frontier Technologies, Breakthrough Science, Smart Information Use, and Promoting an Innovation Economy will thus be advanced.Read moreRead less
Structure and informatics of the genetic code. Recent advances in biotechnology have seen its emergence as a highly
quantitative, numerically-based discipline. To exploit the available
data to the full will require, alongside computing power, new
analytical techniques. This project aims to develop such techniques,
by handling the systematics of the genetic code with methods derived
from theoretical physics and chemistry. Expected outcomes include a
dynamical (quantum field theory) model ....Structure and informatics of the genetic code. Recent advances in biotechnology have seen its emergence as a highly
quantitative, numerically-based discipline. To exploit the available
data to the full will require, alongside computing power, new
analytical techniques. This project aims to develop such techniques,
by handling the systematics of the genetic code with methods derived
from theoretical physics and chemistry. Expected outcomes include a
dynamical (quantum field theory) model of phylogenetic branching,
analyses of nucleic acid structure and content (spin chain models of
RNA binding and of DNA open reading frames), and insights into the
origin of the code itself (via numerical codon similarity measures).
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3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, ....3D Structure determination of biomacromolecular assemblies from sparse data. This project has direct impact on pharmaceutical research: Biomacromolecular interactions are key points for pharmaceutical intervention and detailed structural knowledge of dynamic protein interactions can significantly accelerate drug development. Australia has invested in expensive instrumentation that can be used with new laboratory methods to obtain information on delicately balanced biomacromolecular interactions, and how they malfunction in disease. This project will provide a computational framework to increase the impact of this investment by integrating measurements from a range of novel technologies and developing understanding of changes in structure of large protein complexes in different functional states.Read moreRead less
Theoretical Studies on the KcsA Potassium Channel and the L-type Calcium Channel. All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms is a fundamental problem in biology. The project is aimed at developing a theoretical model of two important types of ion channels. Using a supercomputer, we will first deduce the shape of the microstructure formed by a protein wall. Then, using a computer simulation technique, we will c ....Theoretical Studies on the KcsA Potassium Channel and the L-type Calcium Channel. All electrical activities in the brain are regulated by opening and closing of ion channels. Thus, understanding their mechanisms is a fundamental problem in biology. The project is aimed at developing a theoretical model of two important types of ion channels. Using a supercomputer, we will first deduce the shape of the microstructure formed by a protein wall. Then, using a computer simulation technique, we will construct a set of physical models of biological ion channels, which will correctly replicate experimental observations. Such a theory will link the structure and function of an ion channel through the fundamental principles of physics.Read moreRead less
Self-assembled polyphiles: molecular nanopatterns. 21st century technology is certain to rely on advanced materials, utterly new in character, function and manufacturing process. Control of material structure, from the atomic and molecular scales and upward will be a central focus, to engineer specific features from electronic or photonic functionality, to chemical selectivity. The manufacturing principle of biological materials, made routinely in vivo with exquisite economy and control at all l ....Self-assembled polyphiles: molecular nanopatterns. 21st century technology is certain to rely on advanced materials, utterly new in character, function and manufacturing process. Control of material structure, from the atomic and molecular scales and upward will be a central focus, to engineer specific features from electronic or photonic functionality, to chemical selectivity. The manufacturing principle of biological materials, made routinely in vivo with exquisite economy and control at all length scales, will be adopted for materials design. The route to these materials is self-assembly. We will explore in detail theory and practical manufacture of self-assembled nanostructured materials, building molecular honeycombs combining composite material features at the nanoscale.Read moreRead less
3D Image segmentation and shape characterisation driven by topological persistence. Tomographic imaging is emerging as a new tool to help tackle a remarkable array of scientific challenges. What distinguishes healthy bone from that of osteoporosis sufferers? How does groundwater contamination spread? Why is a macadamia nut so hard to crack? What causes the iridescence in a butterfly wing? These are just a few of the questions being answered at tomographic facilities in Australia alone. By co ....3D Image segmentation and shape characterisation driven by topological persistence. Tomographic imaging is emerging as a new tool to help tackle a remarkable array of scientific challenges. What distinguishes healthy bone from that of osteoporosis sufferers? How does groundwater contamination spread? Why is a macadamia nut so hard to crack? What causes the iridescence in a butterfly wing? These are just a few of the questions being answered at tomographic facilities in Australia alone. By combining sophisticated mathematics with cutting edge image-processing algorithms, this project will yield a new class of topology driven image analysis techniques that will improve the accuracy and reliability of predictions made from tomographic images.Read moreRead less
Mathematical modelling in developmental biology. Modern observational techniques in biology and medicine generate a wealth of genetic and molecular detail. Mathematical modelling integrates and synthesises this information to provide insight into how complex biological processes are coupled to produce experimentally observed behaviour. Mathematical modelling generates experimentally testable predictions that can be used to verify the validity of the models. This program is dedicated to exciting ....Mathematical modelling in developmental biology. Modern observational techniques in biology and medicine generate a wealth of genetic and molecular detail. Mathematical modelling integrates and synthesises this information to provide insight into how complex biological processes are coupled to produce experimentally observed behaviour. Mathematical modelling generates experimentally testable predictions that can be used to verify the validity of the models. This program is dedicated to exciting opportunities for advancing our knowledge of normal and abnormal developmental processes, especially in embryonic growth. Understanding these processes will lead to prediction and treatment of congenital disorders and contribute to a healthy start to life. Read moreRead less
Modelling with stochastic differential equations. We will develop methodology for modelling and analysis of phenomena subjected to random and uncertain influences, such as behaviour of investors in the market, evolution of economy, values of stocks and ant colonies. This methodology will enable scientists to achieve more accurate description and analysis of their models and provide better understanding of these phenomena. Creating the tools for understanding such complex systems will have far re ....Modelling with stochastic differential equations. We will develop methodology for modelling and analysis of phenomena subjected to random and uncertain influences, such as behaviour of investors in the market, evolution of economy, values of stocks and ant colonies. This methodology will enable scientists to achieve more accurate description and analysis of their models and provide better understanding of these phenomena. Creating the tools for understanding such complex systems will have far reaching benefits both nationally and internationally and will allow Australia to strengthen its position in international research. The project will also provide for postgraduate training and international scientific exchange.Read moreRead less