Investigating the biogenesis and function of circular RNAs in the brain. Circular RNAs (circRNAs) are e a novel class of RNA molecules produced in a wide spectrum of eukaryotic organisms, from yeast to humans. Their expression is particularly high in the nervous system in the fruit fly, mouse and humans. What mechanisms are responsible for the tissue-specific enrichment of circular RNA expression? What are the consequences of circular RNA production on gene expression? The overall goal of the pr ....Investigating the biogenesis and function of circular RNAs in the brain. Circular RNAs (circRNAs) are e a novel class of RNA molecules produced in a wide spectrum of eukaryotic organisms, from yeast to humans. Their expression is particularly high in the nervous system in the fruit fly, mouse and humans. What mechanisms are responsible for the tissue-specific enrichment of circular RNA expression? What are the consequences of circular RNA production on gene expression? The overall goal of the proposed project is to elucidate these important aspects of circRNA biogenesis. Specifically, the project aims to (a) discover proteins that regulate circRNA expression, (b) elucidate how circRNA expression interacts with alternative splicing, and (c) identify circular RNAs that play regulatory roles in gene expression. Read moreRead less
How neurons maintain their fate. This project aims to investigate how neurons maintain their identity, without reverting back to less specialised cells. Stable fate maintenance is essential because when it fails, cells lose their ability to perform their ascribed function, which impedes organism fitness. This project aims to define how two proteins work in partnership to maintain the identity of brain neurons. We intend our discoveries to stimulate new research, for example to test whether the h ....How neurons maintain their fate. This project aims to investigate how neurons maintain their identity, without reverting back to less specialised cells. Stable fate maintenance is essential because when it fails, cells lose their ability to perform their ascribed function, which impedes organism fitness. This project aims to define how two proteins work in partnership to maintain the identity of brain neurons. We intend our discoveries to stimulate new research, for example to test whether the human counterparts of the Drosophila proteins studied here, function similarly. Benefits will be provided in the form of job creation, and new knowledge in fundamental aspects of life, including brain development and cell fate maintenance.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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The role of gene isoforms in human brain development. This project aims to investigate how genes vary their products to control human brain development, by creating new methods to study gene activity in individual brain cells. Using these innovative methods, this project expects to generate fundamental new knowledge of how the human brain forms. Expected outcomes of this project include widely applicable techniques, strengthened international (UK) research collaborations and highly trained perso ....The role of gene isoforms in human brain development. This project aims to investigate how genes vary their products to control human brain development, by creating new methods to study gene activity in individual brain cells. Using these innovative methods, this project expects to generate fundamental new knowledge of how the human brain forms. Expected outcomes of this project include widely applicable techniques, strengthened international (UK) research collaborations and highly trained personnel in genomics and neuroscience. This should deliver many benefits, including a better understanding of how the brain forms, training of higher degree by research students, as well as tools and methods of benefit to the academic research and biotechnology sectors.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
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
Discovery of Novel Bacteriophage with the Capacity to Modulate Gut Bacteria. This project aims to experimentally validate the largest ever collection of bacterial viruses (bacteriophages) within the gut microbiome. This project expects to generate new knowledge in the area of bacteriophage biology and genomics by using the innovative approaches of wet-lab and bioinformatic genome analyses. Expect outcomes of this project include the discovery of novel phages using bioinformatics, wet-lab validat ....Discovery of Novel Bacteriophage with the Capacity to Modulate Gut Bacteria. This project aims to experimentally validate the largest ever collection of bacterial viruses (bacteriophages) within the gut microbiome. This project expects to generate new knowledge in the area of bacteriophage biology and genomics by using the innovative approaches of wet-lab and bioinformatic genome analyses. Expect outcomes of this project include the discovery of novel phages using bioinformatics, wet-lab validation of their activity and characterisation of their potential to contribute new bacterial host metabolism. This should provide benefits, such as advancement to our understanding of bacteriophages, improved bioinformatic software, and a characterised collection of commercially valuable bacterial strains and phages.Read moreRead less
Next generation high throughput lipidomics using adaptive modelling. This project aims to develop a unique high-throughput method to capture the lipidomic profile of human plasma suitable for large human population screening. Lipids are fundamental to every biological system, but our understanding of their regulation in humans have been largely superficial. By incorporating a new lipidomics approach, with genomic data, this project aims to expand our understanding of human biology by identifying ....Next generation high throughput lipidomics using adaptive modelling. This project aims to develop a unique high-throughput method to capture the lipidomic profile of human plasma suitable for large human population screening. Lipids are fundamental to every biological system, but our understanding of their regulation in humans have been largely superficial. By incorporating a new lipidomics approach, with genomic data, this project aims to expand our understanding of human biology by identifying regulators of lipid metabolism. The large diversity in humans necessitate sufficient sample sizes to identify true genetic regulators, but to date techniques capturing phenotypic data (lipids) have been largely limited. It is anticipated that this study will identify new regulators of lipid metabolism in humans.Read moreRead less
Decoding regulatory RNA function in bacteria. All complex biological processes in bacterial cells appear to utilise regulatory small RNAs to control gene expression, but we lack a systems-level understanding of their functions and mechanisms of control. This proposal aims to address this fundamental knowledge gap using machine learning and cutting-edge, systems-level techniques to determine how small RNA sequence and structure determines function. Small RNAs have been found to control a broad ra ....Decoding regulatory RNA function in bacteria. All complex biological processes in bacterial cells appear to utilise regulatory small RNAs to control gene expression, but we lack a systems-level understanding of their functions and mechanisms of control. This proposal aims to address this fundamental knowledge gap using machine learning and cutting-edge, systems-level techniques to determine how small RNA sequence and structure determines function. Small RNAs have been found to control a broad range of traits including metabolism, biofilm formation, antibiotic tolerance, and virulence. The work proposed here will enhance our ability to predict and control bacterial gene expression with potential future impacts on bioproduction, synthetic biology, and veterinary and medical microbiology.Read moreRead less
Who’s who in the plant gene world? As many more plant genomes are sequenced, the bottleneck is being able to interrogate and translate this data into applications for crop improvement. This project will develop and apply a population graph database, hosting genome data for the world’s major crops and their wild relatives, allowing the characterisation of gene diversity on an unparalleled scale. Analysis of this data will reveal the presence/absence and sequence diversity for classes of genes for ....Who’s who in the plant gene world? As many more plant genomes are sequenced, the bottleneck is being able to interrogate and translate this data into applications for crop improvement. This project will develop and apply a population graph database, hosting genome data for the world’s major crops and their wild relatives, allowing the characterisation of gene diversity on an unparalleled scale. Analysis of this data will reveal the presence/absence and sequence diversity for classes of genes for important agronomic traits including disease resistance, flowering time and legume nitrogen fixation which will enable plant breeders to identify and apply novel genes and allelic variants for use in breeding programmes, accelerating the production of improved crop varieties.Read moreRead less