SCP/TAPS proteins of the barber’s pole worm. This integrated, collaborative project, will explore, in a targeted way, the structure and function of a key group of molecules in a socio-economically important eukaryotic pathogen and their involvement in pathogen-host interactions. Fundamental knowledge and understanding of these molecules will provide a solid foundation for understanding disease processes and finding new intervention strategies for a range of pathogens. This is crucial, given the ....SCP/TAPS proteins of the barber’s pole worm. This integrated, collaborative project, will explore, in a targeted way, the structure and function of a key group of molecules in a socio-economically important eukaryotic pathogen and their involvement in pathogen-host interactions. Fundamental knowledge and understanding of these molecules will provide a solid foundation for understanding disease processes and finding new intervention strategies for a range of pathogens. This is crucial, given the serious drug resistance problems in pathogens, and residue problems in meat, milk and the environment.Read moreRead less
Statistical methods for detection of non-coding RNAs in eukaryote genomes. Understanding how eukaryotic cells work is a major goal of 21st century biology. A crucial step will be to catalogue the functional components of eukaryotic genomes. Australian researchers must be involved in this process at an early stage, in order to maximise commercial opportunities, attract quality researchers and position ourselves for further advances. This project will make major contributions to international effo ....Statistical methods for detection of non-coding RNAs in eukaryote genomes. Understanding how eukaryotic cells work is a major goal of 21st century biology. A crucial step will be to catalogue the functional components of eukaryotic genomes. Australian researchers must be involved in this process at an early stage, in order to maximise commercial opportunities, attract quality researchers and position ourselves for further advances. This project will make major contributions to international efforts in this area, via the development of statistical methods for segmenting genomes, classification of those segments, and study of the resulting classes. In the long term, enhanced understanding of eukaryotic cells will lead to breakthroughs in biology, and to medical, pharmaceutical, agricultural and scientific advances.Read moreRead less
Alternative Splicing in the Mouse Transcriptome. Although the human genome completion is cause for excitement we do not have any firm indication of precisely how many protein-coding genes exist in a mammalian genome. We have even less indication of the extent to which these genes generate alternative gene products, through a process termed alternative splicing. The detection and sequencing of these full-length alternative gene products is the focus of this application. This application details t ....Alternative Splicing in the Mouse Transcriptome. Although the human genome completion is cause for excitement we do not have any firm indication of precisely how many protein-coding genes exist in a mammalian genome. We have even less indication of the extent to which these genes generate alternative gene products, through a process termed alternative splicing. The detection and sequencing of these full-length alternative gene products is the focus of this application. This application details the opportunity to participate in the identification of the full transcriptome of the mouse and is part of a collaborative effort with The RIKEN Genome Sciences Center in Japan.Read moreRead less
Classification of Microarray Gene-Expression Data. The broad aim is to provide statistical methodology for the classification of microarray gene-expression data. Microarrays are part of a new biotechnology that allows the monitoring of expression levels for thousands of genes simultaneously. The explosion in microarrays has produced massive quantities of data that require new statistical techniques for analysis in order to exploit their enormous scientific potential. One of the main uses of ....Classification of Microarray Gene-Expression Data. The broad aim is to provide statistical methodology for the classification of microarray gene-expression data. Microarrays are part of a new biotechnology that allows the monitoring of expression levels for thousands of genes simultaneously. The explosion in microarrays has produced massive quantities of data that require new statistical techniques for analysis in order to exploit their enormous scientific potential. One of the main uses of the methodology to be developed is to expedite the discovery of new subclasses of diseases. Another is to provide prediction rules for the diagnosis and treatment of diseases.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
Assessing gene function in the developing vertebrate brain using zebrafish as a model system. Although the vertebrate brain is the most complicated biological tissue it arises from a very simple sheet of cells during embryogenesis. Groups of nerve cells begin to communicate with each other through long interconnecting processes called axons. This project seeks to understand the role of specific genes in this process. This is the first time that the mechanisms controlling the growth of the ear ....Assessing gene function in the developing vertebrate brain using zebrafish as a model system. Although the vertebrate brain is the most complicated biological tissue it arises from a very simple sheet of cells during embryogenesis. Groups of nerve cells begin to communicate with each other through long interconnecting processes called axons. This project seeks to understand the role of specific genes in this process. This is the first time that the mechanisms controlling the growth of the earliest axons in the vertebrate brain will be examined in a living brain. Our analysis is expected to discover genes that are targets for manipulation of axon growth.Read moreRead less
Mapping cell wall and surface structures of Gram-positive cocci. The synthesis of the Gram-positive cell wall and protein transport are fundamental processes, the improved understanding of which will impact across a range of fields including microbiology, biochemistry and biotechnology, and the application and manipulation of Gram-positive bacteria in agriculture, industry and human health. In the long-term, the analysis of the Gram-positive ExPortal and cell wall will identify proteins that ma ....Mapping cell wall and surface structures of Gram-positive cocci. The synthesis of the Gram-positive cell wall and protein transport are fundamental processes, the improved understanding of which will impact across a range of fields including microbiology, biochemistry and biotechnology, and the application and manipulation of Gram-positive bacteria in agriculture, industry and human health. In the long-term, the analysis of the Gram-positive ExPortal and cell wall will identify proteins that may represent targets for therapeutic intervention. Additionally a precise understanding of the mechanisms of secretion of anchorless proteins will have an important impact in the biotechnology field, as new methodologies for the secretion of recombinant proteins of industrial value is a potential outcome.Read moreRead less
Early evolutionary origins of mechanosensory transduction: structure, function and phylogenetic studies of the family of mechanosensitive channels in cell-walled organisms. The proposed project is based on the recent progress the applicants have made by (i) identifying a novel family of mechanosensitive (MS) channels in cell-walled organisms, which include Archaea and Bacteria (prokaryotes), as well as fungi and plants (eukaryotes), and (ii) determining basic aspects of the structural dynamics ....Early evolutionary origins of mechanosensory transduction: structure, function and phylogenetic studies of the family of mechanosensitive channels in cell-walled organisms. The proposed project is based on the recent progress the applicants have made by (i) identifying a novel family of mechanosensitive (MS) channels in cell-walled organisms, which include Archaea and Bacteria (prokaryotes), as well as fungi and plants (eukaryotes), and (ii) determining basic aspects of the structural dynamics of MscL, the prototype MS channel, using electronparamagnetic resonance spectroscopy and molecular dynamics simulations in combination with the patch clamp technique. The aim of the project is to elucidate the molecular principles underlying the function of MS channels, which is of fundamental importance for understanding of the biophysics and physiology of mechanosensory transduction throughout the biological world.Read moreRead less
Force from lipids: the role of the lipid bilayer in mechanosensory transduction. The proposed research will significantly contribute to a better understanding of the wide range of physiological processes underlying mechanosensory transduction in living cells. The direct benefit for Australian science consists of: (i) strengthening international links with leading overseas laboratories, and (ii) accessing the state-of-the-art expertise not available in Australia. The acquired knowledge will aid i ....Force from lipids: the role of the lipid bilayer in mechanosensory transduction. The proposed research will significantly contribute to a better understanding of the wide range of physiological processes underlying mechanosensory transduction in living cells. The direct benefit for Australian science consists of: (i) strengthening international links with leading overseas laboratories, and (ii) accessing the state-of-the-art expertise not available in Australia. The acquired knowledge will aid in developing and designing artificial tactile sensors inspired by their biological models studied in this project. Long-term, the project is expected to make an original contribution towards developing new technologies and novel medical applications, both of which promise to be of great national benefit.Read moreRead less
Disulfide Bonds and Protein Folding. This work will advance our understanding of protein folding, which has important implications in biotechnology, impacting on commercial production of recombinant proteins (for pharmaceutical and biomedical applications) and on 1000s of research laboratories worldwide that use recombinant technologies. This research could also contribute to medicine (new treatments for diseases of protein misfolding like Alzheimer's), and to membrane protein structural biology ....Disulfide Bonds and Protein Folding. This work will advance our understanding of protein folding, which has important implications in biotechnology, impacting on commercial production of recombinant proteins (for pharmaceutical and biomedical applications) and on 1000s of research laboratories worldwide that use recombinant technologies. This research could also contribute to medicine (new treatments for diseases of protein misfolding like Alzheimer's), and to membrane protein structural biology. This work could yield economic benefits in the long-term through patentable outcomes and will benefit the community by producing high impact research papers, providing training to Australians and forging links with renowned international scientists.Read moreRead less