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
ARC Centre in Bioinformatics. The Australian Centre for Genome-Phenome Bioinformatics will examine how the genome comes to life in the mammalian cell during differentiation and development. We will model, visualise and experimentally validate the complex cellular systems and regulatory networks that control the transformation of genomic information into biological structure and function. We will develop novel approaches and tools to improve health, optimise agricultural production and exploit ne ....ARC Centre in Bioinformatics. The Australian Centre for Genome-Phenome Bioinformatics will examine how the genome comes to life in the mammalian cell during differentiation and development. We will model, visualise and experimentally validate the complex cellular systems and regulatory networks that control the transformation of genomic information into biological structure and function. We will develop novel approaches and tools to improve health, optimise agricultural production and exploit new cell technologies. The Centre will build critical mass and national focus in bioinformatics to generate the human capital and intellectual property that Australia needs to compete in advanced bioscience and biotechnology.Read moreRead less
A new paradigm of gene regulation - implications in embryogenesis and disease. The proposed analysis of a new paradigm of gene regulation will provide a new key to understanding genome function and inform some of the most compelling biological issues of our time such as stem cell biology, tissue and organ regeneration and genetic programming. The insights and technologies developed in this program will be widely applicable in biotechnological and pharmacogenomic research in Australia and worldwi ....A new paradigm of gene regulation - implications in embryogenesis and disease. The proposed analysis of a new paradigm of gene regulation will provide a new key to understanding genome function and inform some of the most compelling biological issues of our time such as stem cell biology, tissue and organ regeneration and genetic programming. The insights and technologies developed in this program will be widely applicable in biotechnological and pharmacogenomic research in Australia and worldwide, and assert Australia's leadership in this area of research.Read moreRead less
Gene Expression Profiling and de novo Transcriptome Sequencing using Geneballs. The purpose of the project is to demonstrate that bead-based technology can be used in applications that currently require DNA hybridisation in order to overcome existing deficiencies in microarray technology. By providing the capability to quickly and efficiently produce, screen and utilize biomolecule libraries of nearly unlimited size, this technology provides the key to unlock the power of genomics and proteomics ....Gene Expression Profiling and de novo Transcriptome Sequencing using Geneballs. The purpose of the project is to demonstrate that bead-based technology can be used in applications that currently require DNA hybridisation in order to overcome existing deficiencies in microarray technology. By providing the capability to quickly and efficiently produce, screen and utilize biomolecule libraries of nearly unlimited size, this technology provides the key to unlock the power of genomics and proteomics for use in real world applications. The project has two aspects. First, relatively small directed cDNA-bead libraries will be compared to known low-density cDNA microarrays to validate the technique for utility in gene expression profiling. Secondly, large libraries containing short oligonucleotide sequences will be used for de novo sequencing of a complete transcriptome. Proof-of-concept in either case will pave the way for many genomic applications and catapult the technology to 'blockbuster' status.Read moreRead less
Organisation, expression and diversity of the sub-telomeric regions of the ancient eukaryote, Giardia duodenalis. We propose to extend our findings on the extreme plasticity of the structure and organisation of the sub-telomeric region of the complete genome of Giardia by more extensive chromosome walking, and comparison of different isolates. These regions are subject to gene conversion, transcriptional silencing, gene mobility, recombination, variable surface protein expression, subtelomeric i ....Organisation, expression and diversity of the sub-telomeric regions of the ancient eukaryote, Giardia duodenalis. We propose to extend our findings on the extreme plasticity of the structure and organisation of the sub-telomeric region of the complete genome of Giardia by more extensive chromosome walking, and comparison of different isolates. These regions are subject to gene conversion, transcriptional silencing, gene mobility, recombination, variable surface protein expression, subtelomeric instability and the insertion of transposable elements, a dynamic balance between structural conservation and rapid evolution. This is a rare opportunity to understand the forces at work in moulding eukaryotic sub-telomeric sequences because Giardia is not constrained by sexual homogenisation and the dynamic variability is retained.Read moreRead less
The evolution of bacterial pathogenesis: a genomic approach. The outcome of this research will be a better understanding of the genes involved with adaptation to particular pathogenic lifestyles. Specifically, genes that are rapidly evolving in selected bacterial pathogens of medical and veterinary importance will be identified using a bioinformatics approach that exploits the existence of multiple closely-related genome sequences. Such genes encode potential new targets for therapeutic interv ....The evolution of bacterial pathogenesis: a genomic approach. The outcome of this research will be a better understanding of the genes involved with adaptation to particular pathogenic lifestyles. Specifically, genes that are rapidly evolving in selected bacterial pathogens of medical and veterinary importance will be identified using a bioinformatics approach that exploits the existence of multiple closely-related genome sequences. Such genes encode potential new targets for therapeutic intervention that provide alternatives in the face of emerging antibiotic resistance. Importantly, the methodology developed in this project is broadly applicable to the study of evolution of bacterial pathogenesis in any background: medical, agricultural or horticultural.Read moreRead less
The role of mechanosensitive (MS) ion channels in magnetoreception. The magnetic field of the Earth has for long been known to influence the behaviour and orientation of a variety of organisms. Experimental study of the magnetic sense has however, been impaired by the lack of a plausible cellular and/or molecular mechanism providing meaningful explanation for detection of magnetic fields by living organisms. Recently, mechanosensitive (MS) ion channels have been implied to play a role in magneto ....The role of mechanosensitive (MS) ion channels in magnetoreception. The magnetic field of the Earth has for long been known to influence the behaviour and orientation of a variety of organisms. Experimental study of the magnetic sense has however, been impaired by the lack of a plausible cellular and/or molecular mechanism providing meaningful explanation for detection of magnetic fields by living organisms. Recently, mechanosensitive (MS) ion channels have been implied to play a role in magnetoreception. Based on our preliminary investigations, which suggest that the activity of bacterial MS channels may be affected by magnetic fields, we propose to study effects of magnetic fields on MS ion channels in Gram-negative bacteria Escherichia coli and Magnetospirillum magnetotacticum. The project promises also to contribute towards better understanding of adverse effects of electromagnetic radiation on human health and towards understanding the mechanisms behind remote magnetic-nanoparticle mediated activation of MS ion channels.Read moreRead less
Insect host/vector genetic responses to rhabdovirus infection. Rhabdoviruses cause important diseases in humans, animals and plants. These viruses are transmitted by insect vectors in which they persist and propagate, an intimate and specific association. Insect-rhabdovirus interactions will be studied at the molecular level using a planthopper-maize rhabdovirus model. Insect genes specifically induced by rhabdovirus infection as well as the viral genes themselves will be identified and characte ....Insect host/vector genetic responses to rhabdovirus infection. Rhabdoviruses cause important diseases in humans, animals and plants. These viruses are transmitted by insect vectors in which they persist and propagate, an intimate and specific association. Insect-rhabdovirus interactions will be studied at the molecular level using a planthopper-maize rhabdovirus model. Insect genes specifically induced by rhabdovirus infection as well as the viral genes themselves will be identified and characterized using genomics and bioinformatics tools. We will extend the same approaches to a comparative analysis of these planthopper genes with other insect-rhabdovirus systems under investigation in our institutes. Identification of viral genes expressed in insects, the insect genes that respond to virus infection, and interpretation of the roles of these genes in insects, may indicate new opportunities to control serious plant and animal diseases through control of virus transmission.Read moreRead less
The molecular basis of cold adaptation: an integrated genomic and proteomic study of Antarctic archaea. The project enables Australia to remain a world leader in extremophiles, cold adaptation and Antarctic biology, strengthening the reputation Australian scientists have in scientific programs of global significance and fostering the interests of the international community in sciences ranging from bioprospecting to the search for extraterrestrial life. National benefit is directly derived from ....The molecular basis of cold adaptation: an integrated genomic and proteomic study of Antarctic archaea. The project enables Australia to remain a world leader in extremophiles, cold adaptation and Antarctic biology, strengthening the reputation Australian scientists have in scientific programs of global significance and fostering the interests of the international community in sciences ranging from bioprospecting to the search for extraterrestrial life. National benefit is directly derived from technological innovation and training local scientists in modern biology of environmental microorganisms. The Antarctic microorganisms provide unique compounds, enzymes and molecules for biotechnology and industry. Insight will be gained into the critical role that methanogens play in the global carbon cycle and global warming.Read moreRead less
Genetical Genomics of Mutational Variance. Mutation is the ultimate source of all genetic variation. Understanding the nature of mutation, its frequency, the distribution of effects, and the forces of selection that remove mutational load from populations is therefore a central concern of genetics. The accumulation of mutational load both in endangered species and human populations, where the natural forces of selection tend not to operate, has the potential to create serious problems in these p ....Genetical Genomics of Mutational Variance. Mutation is the ultimate source of all genetic variation. Understanding the nature of mutation, its frequency, the distribution of effects, and the forces of selection that remove mutational load from populations is therefore a central concern of genetics. The accumulation of mutational load both in endangered species and human populations, where the natural forces of selection tend not to operate, has the potential to create serious problems in these populations. The goal is to understand what types of mutations are targeted by selection at the gene expression level and why.Read moreRead less