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
Mutagenesis and combinatorial algorithms for sequencing problematic genomic regions. This project will develop a remarkable and original approach to DNA sequencing with potential to radically improve the speed, accuracy and effectiveness of existing sequencing technologies. It is especially useful for dealing with difficult-to-sequence genomic regions and has implications for all sequencing projects, including completion of the Human Genome Project. The approach involves generating, and wholly o ....Mutagenesis and combinatorial algorithms for sequencing problematic genomic regions. This project will develop a remarkable and original approach to DNA sequencing with potential to radically improve the speed, accuracy and effectiveness of existing sequencing technologies. It is especially useful for dealing with difficult-to-sequence genomic regions and has implications for all sequencing projects, including completion of the Human Genome Project. The approach involves generating, and wholly or partially sequencing, mutated copies of problematic regions of the target genome. Advanced combinatorial algorithms are then used to form highly probable alignments between strings and determine the unknown sequence. The approach has additional benefits in detecting single-nucleotide polymorphisms and sequencing errors.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
Recombination of mitochondrial genomes: what can we learn from chigger mites? This project will bring three benefits to Australia. First, it will enhance Australia's research capacity in the fields of organelle genomics and evolutionary biology. Second, it will yield highly skilled young researchers: a postdoctoral fellow (Shao), a PhD student and two BSc Honours students. Third, it will generate new knowledge about genome recombination in animal mitochondria. Recombination is a fundamental, yet ....Recombination of mitochondrial genomes: what can we learn from chigger mites? This project will bring three benefits to Australia. First, it will enhance Australia's research capacity in the fields of organelle genomics and evolutionary biology. Second, it will yield highly skilled young researchers: a postdoctoral fellow (Shao), a PhD student and two BSc Honours students. Third, it will generate new knowledge about genome recombination in animal mitochondria. Recombination is a fundamental, yet poorly understood issue in mitochondrial genomics and evolutionary biology. Knowledge from this project will also improve our understanding of other important issues that are associated with animal mitochondria; like the mechanisms of mitochondrial disease and ageing, and the evolution of modern humans and other animals.Read moreRead less
Sex and bottlenecks: understanding the evolutionary dynamics of bacterial adaptation. Bacteria can rapidly adapt to changing environments, often with devastating consequences for humans. However, this adaptive evolution is often limited by strong reductions in population size, in particular during transmission from one host to another. This project aims to investigate whether recombination in bacteria can overcome the limits that such bottlenecks impose on the rate of adaptation. To this end, it ....Sex and bottlenecks: understanding the evolutionary dynamics of bacterial adaptation. Bacteria can rapidly adapt to changing environments, often with devastating consequences for humans. However, this adaptive evolution is often limited by strong reductions in population size, in particular during transmission from one host to another. This project aims to investigate whether recombination in bacteria can overcome the limits that such bottlenecks impose on the rate of adaptation. To this end, it will construct mathematical models and complement them with evolution experiments in bacterial populations. Results from this research aim to generate fundamental insights into the role of recombination in bacterial evolution and will provide guidance for developing management strategies for bacterial pathogens.Read moreRead less
Predicting the evolutionary dynamics of adaptation. This project aims to address the question of how we can predict adaptive evolution. The project aims to probe the limits of evolutionary predictions by using a model system of bacterial populations that adapt to the presence of multiple stressors. This will be combined with high-throughput fitness measurements, whole genome sequencing and computer simulations. Anticipated outcomes include novel insights into deep questions regarding the structu ....Predicting the evolutionary dynamics of adaptation. This project aims to address the question of how we can predict adaptive evolution. The project aims to probe the limits of evolutionary predictions by using a model system of bacterial populations that adapt to the presence of multiple stressors. This will be combined with high-throughput fitness measurements, whole genome sequencing and computer simulations. Anticipated outcomes include novel insights into deep questions regarding the structure of fitness landscapes and the repeatability, predictability and contingency of adaptive evolution. The project is expected to provide significant benefits, informing the development of improved strategies for managing pathogen resistance to antimicrobial drugs.Read moreRead less
Actin cytoskeleton regulation by E-cadherin and Src. This project examines a fundamental, novel mechanism of how cells work together in tissues. It will provide important new knowledge about how tissues become organized in health, and how organization might be disturbed in disease. It will build Australia's skill base in cutting-edge scientific research, and promote knowledge directed to the research priority area of Promoting and Maintaining Good Health.
How the Y Chromosome makes a male: Molecular genetic analysis of key sex-determining genes. Sex reversal and intersex syndromes are among the most common and highly stigmatized disorders affecting newborn babies. Our research will reveal how the Y chromosome regulates normal male development, identify the steps that go wrong in many male babies, and suggest ways to diagnose and deal with these conditions. It will also pave the way for biotechnological applications in the areas of stem cell techn ....How the Y Chromosome makes a male: Molecular genetic analysis of key sex-determining genes. Sex reversal and intersex syndromes are among the most common and highly stigmatized disorders affecting newborn babies. Our research will reveal how the Y chromosome regulates normal male development, identify the steps that go wrong in many male babies, and suggest ways to diagnose and deal with these conditions. It will also pave the way for biotechnological applications in the areas of stem cell technology, pest management, wildlife conservation and animal breeding.Read moreRead less
MOLECULAR GENETICS OF MAMMALIAN SEXUAL DEVELOPMENT: Molecular roles of SRY and SOX9. The development of sexual characteristics is critical to the survival of almost all animal species. This project seeks to clarify how male and female embryos develop differently, focusing on the Y-chromosome maleness gene Sry, and a closely related and equally important gene Sox9. We will study how these genes are switched on in developing gonads and how they interact with other genes to bring about testis forma ....MOLECULAR GENETICS OF MAMMALIAN SEXUAL DEVELOPMENT: Molecular roles of SRY and SOX9. The development of sexual characteristics is critical to the survival of almost all animal species. This project seeks to clarify how male and female embryos develop differently, focusing on the Y-chromosome maleness gene Sry, and a closely related and equally important gene Sox9. We will study how these genes are switched on in developing gonads and how they interact with other genes to bring about testis formation in male embryos. In this way we will discover new genes and mechanisms that are important for sexual identity and also other aspects of embryo development.Read moreRead less