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
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
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
How and why cells decorate their genetic messages. This project aims to investigate a new layer of genomic control mediated not by DNA but instead by chemical modifications found on the cell's working copies of genetic information called messenger RNA. The investigations will use cutting-edge RNA sequencing technology and the fruit fly model organism to uncover the scope and mechanisms by which such modifications enact their roles at the molecular level and within the body plan of an animal. Exp ....How and why cells decorate their genetic messages. This project aims to investigate a new layer of genomic control mediated not by DNA but instead by chemical modifications found on the cell's working copies of genetic information called messenger RNA. The investigations will use cutting-edge RNA sequencing technology and the fruit fly model organism to uncover the scope and mechanisms by which such modifications enact their roles at the molecular level and within the body plan of an animal. Expected outcomes include novel molecular tools and models that will assist in understanding and manipulating the function of genomes. Such knowledge should provide benefits in developing innovative biotechnology applications of use in human health, agriculture and managing the environment.
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Prognosis based network-type feature extraction for complex biological data. This project aims to develop statistical tools that integrate high-throughput molecular data with biological knowledge to make discoveries in complex diseases. This project uses machine learning methods, statistical models and proteomic platforms to identify relationships among clinico-pathologic and molecular measurements. It will produce tools and insights that are intended to accelerate the process of biologically an ....Prognosis based network-type feature extraction for complex biological data. This project aims to develop statistical tools that integrate high-throughput molecular data with biological knowledge to make discoveries in complex diseases. This project uses machine learning methods, statistical models and proteomic platforms to identify relationships among clinico-pathologic and molecular measurements. It will produce tools and insights that are intended to accelerate the process of biologically and clinically significant discoveries in biomedical research. This project will help Australian researchers in statistics and users of statistics (from fields as diverse as biology, ecology, medicine, finance, agriculture and the social sciences) to make better predictions that are easier to understand.Read moreRead less
Three-dimensional structure determination of biomolecular assemblies from sparse data of different length scales. New computer algorithms will be combined with sparse experimental structure restraints, obtained with novel protein chemistry technologies, to generate accurate three-dimensional (3D) models of proteins and protein assemblies in solution and in the solid state. The new strategies will greatly increase the number of protein targets amenable to rational drug design.
Evolutionary analyses of short-read sequences from pooled samples. This project aims to provide biologists with a means of making sound, statistical inferences about evolution by using next-generation data from mixed samples. When biologists make statements about history, they use evolutionary trees, frequently reconstructed from the genetic data of many individuals. Next-generation sequencing provides large amounts of genetic data at low cost, but biologists have difficulty using these data for ....Evolutionary analyses of short-read sequences from pooled samples. This project aims to provide biologists with a means of making sound, statistical inferences about evolution by using next-generation data from mixed samples. When biologists make statements about history, they use evolutionary trees, frequently reconstructed from the genetic data of many individuals. Next-generation sequencing provides large amounts of genetic data at low cost, but biologists have difficulty using these data for evolutionary research, particularly when they sample mixtures of DNA from many individuals. The anticipated value of this project is that it allows evolutionary biologists to capitalise on the benefits of next-generation sequencing, without sacrificing their ability to make reliable inferences about history.Read moreRead less