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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Genome-wide discovery of translation control mechanisms. This project aims to reveal currently unknown molecular details of protein synthesis, a step of gene expression that is central to all of life. To achieve this, innovative methods based on next-generation sequencing will be deployed in the yeast model organism. Yeasts are of importance as pathogens as well as in the food and biotechnology industry sector. Thus, new knowledge generated in this project will help solve problems of invasive pa ....Genome-wide discovery of translation control mechanisms. This project aims to reveal currently unknown molecular details of protein synthesis, a step of gene expression that is central to all of life. To achieve this, innovative methods based on next-generation sequencing will be deployed in the yeast model organism. Yeasts are of importance as pathogens as well as in the food and biotechnology industry sector. Thus, new knowledge generated in this project will help solve problems of invasive pathogenic behaviour and biomass production.Read moreRead less
How novel ribosomal RNA gene repeat variants drive cellular function. The hundreds of ribosomal RNA gene repeat copies are a remarkable part of our genomes, as they encode the machinery responsible for all cellular protein synthesis and shape the structure of the nucleus. However, due to their high degree of sequence similarity, they still have not been assembled into the human genome reference. This project will resolve this impasse and furthermore uncover the functional impacts of a newly iden ....How novel ribosomal RNA gene repeat variants drive cellular function. The hundreds of ribosomal RNA gene repeat copies are a remarkable part of our genomes, as they encode the machinery responsible for all cellular protein synthesis and shape the structure of the nucleus. However, due to their high degree of sequence similarity, they still have not been assembled into the human genome reference. This project will resolve this impasse and furthermore uncover the functional impacts of a newly identified molecular diversity in the ribosomal RNA gene repeats. Outcomes include new paradigms for how the ribosomal RNA gene repeats drive protein synthesis and genome structure, and a blueprint to develop novel genomics applications for human health, biotechnology, and agriculture.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
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.