The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with res ....The MYB gene as a model for global transcriptional regulation: stopping, starting and looping. This project will study how transcriptional elongation controls the MYB gene, a key regulator of normal and cancerous growth and regulation. There are three major benefits that are likely to flow from the proposed research It will strengthen research in new and important areas of transcriptional regulation, by building research capacity in Australia in the area of gene expression, particularly with respect to transcriptional elongation and long-range regulation. It will highlight a new approach to the therapeutic targeting of MYB in cancer: data generated from this research may enable us to target MYB expression in a range of cancers including breast cancer by inhibiting transcriptional elongation. And it will provide training in advanced molecular biology to postdoctoral scientists and students.Read moreRead less
Co-ordinated Action of ATM and DNA-PK in DNA damage recognition. The aim of this project is to investigate the mechanism of repair of double straind breaks in DNA sustained after radiation damage. Specifically we will focus on two proteins ATM (mutated in the genetic disorder ataxia-telangiectasia) and DNA-PK mutated in scid mice. There two proteins recognize double straind breaks in DNA and signal this damage to the DNA repair machinery of the cell and to cell cycle checkpoints. The emphasis ....Co-ordinated Action of ATM and DNA-PK in DNA damage recognition. The aim of this project is to investigate the mechanism of repair of double straind breaks in DNA sustained after radiation damage. Specifically we will focus on two proteins ATM (mutated in the genetic disorder ataxia-telangiectasia) and DNA-PK mutated in scid mice. There two proteins recognize double straind breaks in DNA and signal this damage to the DNA repair machinery of the cell and to cell cycle checkpoints. The emphasis here will be in the relationship between the two proteins in co-ordinating the repair of breaks in DNA. This information will be important in understanding mechanisms for maintaining the integrity of the genome.Read moreRead less
The making of a sea shell: function and evolution of genes encoding calcareous architectures of phenomenal strength, purity and beauty. The mollusc shell is composed of microscopic layers of tabular calcium carbonate crystals and thin sheets of proteins with precise nanoscale architectures. This configuration produces a high-performance composite material that exceeds the present capabilities of human engineering. This integrated study will elucidate the molecular mechanisms controlling the fab ....The making of a sea shell: function and evolution of genes encoding calcareous architectures of phenomenal strength, purity and beauty. The mollusc shell is composed of microscopic layers of tabular calcium carbonate crystals and thin sheets of proteins with precise nanoscale architectures. This configuration produces a high-performance composite material that exceeds the present capabilities of human engineering. This integrated study will elucidate the molecular mechanisms controlling the fabrication of these architectures. This knowledge will contribute significantly to the development of materials for advanced electronics and energy transducers, human bone therapeutics and marine?based products such as pearls and cements, through the identification of genes underlying biofabrication networks and the development of in vitro bioproduction systems. Read moreRead less
The link between environmental stress and disease onset in prawn aquaculture. The federal government has set a target for prawn aquaculture production to increase fourfold by 2010. A major barrier is disease: losses of 20% of production to viral diseases are not uncommon. To be internationally competitive, Australia needs to develop high health production systems. Most prawn stock carry chronic viral infections, but only exhibit disease symptoms following environmental stress. This project will ....The link between environmental stress and disease onset in prawn aquaculture. The federal government has set a target for prawn aquaculture production to increase fourfold by 2010. A major barrier is disease: losses of 20% of production to viral diseases are not uncommon. To be internationally competitive, Australia needs to develop high health production systems. Most prawn stock carry chronic viral infections, but only exhibit disease symptoms following environmental stress. This project will identify environmental stressors that activate viral disease in Penaeus monodon. Outcomes will be incorporated into on-farm managerial regimes to minimize risk of crop loss to disease. Development of biomarkers as indicators of stress related risks may be commercialized.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
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
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
Discovery of pathways to embryogenesis in pathogenic flatworm parasites using microdissection and transcriptomic technologies. The cost to Australia of flatworm parasites to animal production and human health is substantial (hundreds of millions of dollars per year). This research will give new insights into how flatworms reproduce and equip their progeny for survival, providing impetus for new vaccine or drug therapies to be developed. As these pathogens are more significant in Australia's ne ....Discovery of pathways to embryogenesis in pathogenic flatworm parasites using microdissection and transcriptomic technologies. The cost to Australia of flatworm parasites to animal production and human health is substantial (hundreds of millions of dollars per year). This research will give new insights into how flatworms reproduce and equip their progeny for survival, providing impetus for new vaccine or drug therapies to be developed. As these pathogens are more significant in Australia's near neighbours, this project will strengthen Australia's international leadership in this field. Our study will provide, for the first time for any helminth parasite, a freely available genetic database that profiles the gene expression repertoire of individual parasite tissues, a development likely to enhance the international effort in controlling these harmful diseases.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