Many Ys in monotremes: multiple sex chromosomes and sex determination in platypus and echidna. Platypus and Echidna are Australian icons, even featuring on our coins. Their unusual biology and ancient relationship to humans make them unique for understanding the mammalian genome, as demonstrated by our recent discovery of ten sex chromosomes in platypus that link mammal and bird sex. Still little is known about their genome, embryo development and how sex is determined. We will identify new gene ....Many Ys in monotremes: multiple sex chromosomes and sex determination in platypus and echidna. Platypus and Echidna are Australian icons, even featuring on our coins. Their unusual biology and ancient relationship to humans make them unique for understanding the mammalian genome, as demonstrated by our recent discovery of ten sex chromosomes in platypus that link mammal and bird sex. Still little is known about their genome, embryo development and how sex is determined. We will identify new genes on all ten sex chromosomes and investigate how they determine sex. The set up of an Australian Monotreme Resource Centre will be crucial for this research and attract worldwide high profile collaborations. We will answer important general questions in monotreme biology and contribute to our understanding of sexual abnormalities in humans.Read moreRead less
Structure and function of heterodimeric amino acid transporters. Recently a new family of amino acid transporters has been identified, the members of which are involved in the delivery of amino acids between cells and tissues. All members display a rather unusual structure in that they require two subunits to be functional. The main aim of this study is to investigate the interaction between large and small subunits. The study will give insight how membrane proteins form complexes in the membran ....Structure and function of heterodimeric amino acid transporters. Recently a new family of amino acid transporters has been identified, the members of which are involved in the delivery of amino acids between cells and tissues. All members display a rather unusual structure in that they require two subunits to be functional. The main aim of this study is to investigate the interaction between large and small subunits. The study will give insight how membrane proteins form complexes in the membrane and how these interactions affect the function of a complex membrane protein.Read moreRead less
Mechanism of higher-order chromatin formation and its role in controlling gene expression. The organization of genomic DNA into chromatin has solved one of the most difficult engineering problems required for the development of a multicellular organism; the compaction of over two meters DNA into a cell almost one millionth this size. Importantly, this compaction of the genome into chromatin has also been exploited by the cell to regulate the expression of genes. The aim of this investigation is ....Mechanism of higher-order chromatin formation and its role in controlling gene expression. The organization of genomic DNA into chromatin has solved one of the most difficult engineering problems required for the development of a multicellular organism; the compaction of over two meters DNA into a cell almost one millionth this size. Importantly, this compaction of the genome into chromatin has also been exploited by the cell to regulate the expression of genes. The aim of this investigation is to elucidate how genes are assembled into complex active or inactive chromatin structures by employing a novel in vitro system. This information will have important implications for gene therapy strategies.
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The Dynamic Control of Chromatin Structure. A human chromosome is a highly heterogeneous global structure because along its axis, it folds to different extents to form either highly compacted domains that repress the expression of genes or less condensed regions that enable genes to be turned on. Changes to the structure or stability of chromosomes, and the corresponding alterations to gene expression, have been linked to many diseases states like defects in human development and cancer. This s ....The Dynamic Control of Chromatin Structure. A human chromosome is a highly heterogeneous global structure because along its axis, it folds to different extents to form either highly compacted domains that repress the expression of genes or less condensed regions that enable genes to be turned on. Changes to the structure or stability of chromosomes, and the corresponding alterations to gene expression, have been linked to many diseases states like defects in human development and cancer. This study will uncover the underpinning mechanism of how our chromosomes are organised into distinct functional domains, which may offer the potential to develop new strategies to correct chromosomal abnormalities.
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Suction pipette measurements of mammalian rod photoreceptor recovery following intense bleaching exposures. The aim of this project is to discover the events and processes that prevent retinal photoreceptors from recovering instantaneously following the cessation of exposure to extremely bright illumination. Recordings will be made from single rod photoreceptors cells isolated from the mammalian retina. The work will uncover the relative roles of the 'photoproducts' created when rhodopsin abso ....Suction pipette measurements of mammalian rod photoreceptor recovery following intense bleaching exposures. The aim of this project is to discover the events and processes that prevent retinal photoreceptors from recovering instantaneously following the cessation of exposure to extremely bright illumination. Recordings will be made from single rod photoreceptors cells isolated from the mammalian retina. The work will uncover the relative roles of the 'photoproducts' created when rhodopsin absorbs light: e.g. intermediates such as metarhodopsin and opsin. The molecular knowledge obtained will help us to understand why it is that the visual system recovers so slowly after the eye has experienced very intense light.Read moreRead less
The first stage of vision: transduction and adaptation in retinal photoreceptors. The project aims to provide a detailed understanding of the molecular steps involved in the first stage of vision - the conversion of light into a neural signal in the rod and cone photoreceptors of the retina. The significance of this is that it will explain the initial events that enable us to see, and will help explain the deficits that occur when the process fails. The outcome will be a comprehensive understand ....The first stage of vision: transduction and adaptation in retinal photoreceptors. The project aims to provide a detailed understanding of the molecular steps involved in the first stage of vision - the conversion of light into a neural signal in the rod and cone photoreceptors of the retina. The significance of this is that it will explain the initial events that enable us to see, and will help explain the deficits that occur when the process fails. The outcome will be a comprehensive understanding of how our photoreceptors respond with extreme sensitivity, yet great rapidity, and over an enormous range of light intensities, thus endowing us with our remarkable sense of vision.Read moreRead less
Thermo-electro-chemo-mechanical properties of biological systems. The proposal is aimed at developing a new theoretical framework for piezoelectric biological materials and structures, through theoretical analysis, computation and numerical simulations, as well as experimental investigations, to produce high-reliability, high-performance hydrogel components and smart soft tissue structures. It is envisaged that successful outcomes of this program will give the Australian biological industry a te ....Thermo-electro-chemo-mechanical properties of biological systems. The proposal is aimed at developing a new theoretical framework for piezoelectric biological materials and structures, through theoretical analysis, computation and numerical simulations, as well as experimental investigations, to produce high-reliability, high-performance hydrogel components and smart soft tissue structures. It is envisaged that successful outcomes of this program will give the Australian biological industry a technology edge over their competitors and provide easy-to-use guidelines for the design of smart biological systems.Read moreRead less
Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operati ....Realistic models of permeation in ion channels. Ion channels are formed by proteins in cell membranes and provide pathways for fast and controlled flow of selected ions. This activity generates action potentials in nerves and muscles that forms the basis of all movement, sensation and thought processes. Recent determination of the crystal structure of channel proteins has enabled construction of models that can relate channel function to its structure--necessary for understanding their operation and seeking cures for diseases caused by their malfunction. This project aims to develop accurate ion-protein-water interactions for permeation models based on stochastic and molecular dynamics simulations using both classical and quantum mechanical methods.Read moreRead less
Adaptive Evolution of BRCA1 in Ancestral Mammals. This project investigates adaptive evolution of BRCA1 in the early radiation of mammals. We will test the hypothesis that the evolution of mammary glands and X chromosome inactivation has resulted in modification of the BRCA1 protein sequence as it aquired new roles in these processes. We will also investigate the importance of these changes inducing compensatory changes in other parts of the protein.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0883032
Funder
Australian Research Council
Funding Amount
$1,300,000.00
Summary
800 MHz NMR spectrometer for biomolecular structure-function analysis. An understanding of how organisms function at the molecular level is central to developing the ability to fight many diseases in a rational way. This equipment will provide the capability for many different laboratories around NSW and the ACT to advance our knowledge at this fundamental level, primarily by examining the structures and functions of biomolecules such as proteins.