Preparing Australia For Genomic Medicine: A Proposal By The Australian Genomics Health Alliance
Funder
National Health and Medical Research Council
Funding Amount
$25,000,000.00
Summary
The sequencing of the human genome brings the possibility of more accurate identification of the underlying basis of many diseases. This technology has moved so rapidly, however, that clinical access has been limited. In this application, a national alliance of clinicians, researchers, health economists and policymakers will evaluate the case for clinical genomics across inherited disease and cancer, determine how best to deliver this to the patient and train a capable workforce.
Genome evolution & adaptation of the multinuclear wheat stripe rust fungus. Animals and plants package their genomes into a single nucleus within each cell. In contrast, millions of fungal species accommodate multiple nuclei containing individual haploid genomes. It is currently unknown what the evolutionary implications are for this unusual genome division into multiple nuclei. Here we explore the evolutionary consequences of genome division into multiple nuclei for the first time by applying c ....Genome evolution & adaptation of the multinuclear wheat stripe rust fungus. Animals and plants package their genomes into a single nucleus within each cell. In contrast, millions of fungal species accommodate multiple nuclei containing individual haploid genomes. It is currently unknown what the evolutionary implications are for this unusual genome division into multiple nuclei. Here we explore the evolutionary consequences of genome division into multiple nuclei for the first time by applying cutting edge genome biology tools and algorithms. The economically significant study system is the devastating wheat stripe rust fungus. This pathogen costs Australian farmers over $100 million a year. New understanding is expected to lead to better disease management, reduced fungicide applications, and increased yields.Read moreRead less
Understanding somatic mutation in plants: new methods, new software, new data. Somatic mutations accumulate as plants grow, affecting everything from short-term ecological interactions to long-term evolutionary dynamics. These mutations have important consequences for plant industry and conservation, but because they are so hard to measure almost nothing is known about them. This project aims to develop new methods and software to detect, analyse, and compare the genome-wide history of somatic m ....Understanding somatic mutation in plants: new methods, new software, new data. Somatic mutations accumulate as plants grow, affecting everything from short-term ecological interactions to long-term evolutionary dynamics. These mutations have important consequences for plant industry and conservation, but because they are so hard to measure almost nothing is known about them. This project aims to develop new methods and software to detect, analyse, and compare the genome-wide history of somatic mutation in individual plants, providing an unprecedented level of detail into an important but understudied source of biological variation. By applying these methods to an iconic experimental population, This project aims to provide the first insights into the genome-wide causes and consequences of somatic mutation in plants.Read moreRead less
Visual Analytics for Next Generation Sequencing. Next-generation sequencing technologies have brought a revolution in biology and healthcare, while taxing the ability of scientists and clinicians to identify and process relevant data, to make sense of it all and communicate it to others in a concise and meaningful way. This project aims to tackle this problem through fundamentally new approaches to data selection and visualisation at very large scale, actively encoding for insight into underlyin ....Visual Analytics for Next Generation Sequencing. Next-generation sequencing technologies have brought a revolution in biology and healthcare, while taxing the ability of scientists and clinicians to identify and process relevant data, to make sense of it all and communicate it to others in a concise and meaningful way. This project aims to tackle this problem through fundamentally new approaches to data selection and visualisation at very large scale, actively encoding for insight into underlying biological and biomedical processes, bringing sustainable discovery of new relationships and variations within the data. The project aims to support new approaches to medical diagnosis and treatment, and offer crucial lessons to address the broader challenge of understanding large, complex data sets.Read moreRead less
RNA-binding proteins rewire transcriptomes in immune cell differentiation. This project aims to combine advanced computational and experimental techniques to investigate a new layer of gene regulation by novel RNA binding proteins (RBP) which control messenger RNA length in immune cells. This project expects to demonstrate that these RBPs have a profound effect on immune cell differentiation and response to infection. Expected outcomes include the discovery of new RBPs regulating immunity, with ....RNA-binding proteins rewire transcriptomes in immune cell differentiation. This project aims to combine advanced computational and experimental techniques to investigate a new layer of gene regulation by novel RNA binding proteins (RBP) which control messenger RNA length in immune cells. This project expects to demonstrate that these RBPs have a profound effect on immune cell differentiation and response to infection. Expected outcomes include the discovery of new RBPs regulating immunity, with mechanism and function determined by novel CRISPR editing of a transgenic mouse model. The significant benefit will be a more complete understanding of RNA mechanisms of immune response, which will be critical in informing future advances in the rapidly developing areas of RNA-based biotechnologies and synthetic immunology.Read moreRead less
How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, ....How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, this project expects to provide insights into non-coding regulatory element reprogramming and control of immune cell function and memory with implications for understanding general cellular differentiation.Read moreRead less
Variation in the arginine vasopressin 1a receptor (AVPR1a) gene, the social environment, general health and wellbeing. The project aims to investigate how the arginine vasopressin 1a gene affects gene expression and influences social behaviour and ultimately health and wellbeing. This research will contribute to understanding the importance of individual differences in social policy and interventions aimed at improving health and wellbeing.
Evolving rates: foundations for the next generation of molecular clocks. This project aims to investigate the causes and consequences of variation in rate of DNA sequence evolution across three kingdoms of life. Dates estimated from DNA sequences have a wide range of applications, including evolutionary biology, conservation prioritisation and epidemiology. These methods rely on accurate rate estimates, but current models lack information about the biological drivers of rates of genomic change. ....Evolving rates: foundations for the next generation of molecular clocks. This project aims to investigate the causes and consequences of variation in rate of DNA sequence evolution across three kingdoms of life. Dates estimated from DNA sequences have a wide range of applications, including evolutionary biology, conservation prioritisation and epidemiology. These methods rely on accurate rate estimates, but current models lack information about the biological drivers of rates of genomic change. This project will test reliability of current methods, identify potentially misleading estimates of disease origin or conservation priorities, and develop new approaches with empirically-informed models of rate change.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE190100491
Funder
Australian Research Council
Funding Amount
$418,386.00
Summary
Linking genomic changes to the generation of biodiversity. This project aims to provide a suite of theories, methods and software to enhance our understanding on how the generation of variation at molecular level is linked to the generation of species richness at lineage level. This new approach tests various ways that molecular changes are manifested as patterns of diversification, as revealed by genomic data analysed at the lineage level in phylogenetic studies. Expected outcomes of this proje ....Linking genomic changes to the generation of biodiversity. This project aims to provide a suite of theories, methods and software to enhance our understanding on how the generation of variation at molecular level is linked to the generation of species richness at lineage level. This new approach tests various ways that molecular changes are manifested as patterns of diversification, as revealed by genomic data analysed at the lineage level in phylogenetic studies. Expected outcomes of this project add to a growing body of evolutionary theory and provide practical phylogenetic tools for future analyses. These should benefit Australia by improving our understanding on the formation of Australia’s biodiversity hotspots.Read moreRead less
Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins ....Methods for Protein Structure Analysis by Electron Paramagnetic Resonance. This highly interdisciplinary project aims to establish new tools to analyse the structure and motions of proteins that are otherwise difficult to study. A combination of advanced biochemistry, modern magnetic spectroscopy methods, and high-performance computing techniques will be applied to study proteins at physiological concentrations and in complex environments. New techniques will be developed and tested on proteins of high biochemical or biomedical importance, and the approach will be applied to established drug targets.Read moreRead less