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
Hidden complexity in microRNA function. This project aims to determine the extent to which microRNAs function through “non-canonical” mechanisms within cell nuclei, how their roles are expanded by naturally occurring sequence variation and how their activity is controlled by little known families of genes that sequester and inhibit their availability. The knowledge generated is significant as microRNAs regulate the expression of virtually all genes and biological processes, yet these mechanisms ....Hidden complexity in microRNA function. This project aims to determine the extent to which microRNAs function through “non-canonical” mechanisms within cell nuclei, how their roles are expanded by naturally occurring sequence variation and how their activity is controlled by little known families of genes that sequester and inhibit their availability. The knowledge generated is significant as microRNAs regulate the expression of virtually all genes and biological processes, yet these mechanisms of function remain poorly characterised and seldom considered. The expected outcome of better understanding mechanisms through which microRNAs work should provide significant benefit to safe and effective development of microRNAs for future agricultural or therapeutic application.Read moreRead less
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
Metabolic control of gene expression networks and microbiome interactions. The proposal aims to advance our understanding of how metabolism (and resulting metabolites) regulate the expression of genes, and investigate how these processes dictate the interaction of microbiota with the immune system. The project is expected to generate transformative knowledge of gene regulation, a fundamental process for cellular function, and decipher how the microbiome yeast Candida albicans interacts with immu ....Metabolic control of gene expression networks and microbiome interactions. The proposal aims to advance our understanding of how metabolism (and resulting metabolites) regulate the expression of genes, and investigate how these processes dictate the interaction of microbiota with the immune system. The project is expected to generate transformative knowledge of gene regulation, a fundamental process for cellular function, and decipher how the microbiome yeast Candida albicans interacts with immune cells and bacteria. By utilising a powerful combination of molecular and systems biology with molecular genetics and imaging, the project outcomes should foster interdisciplinary collaborations and build capacity for fundamental and applied research to benefit academia and industry, locally and globally.Read moreRead less
How does the noncoding genome regulate gene expression in the human brain? The non-coding genome is recognized as a major player in orchestrating gene expression in higher eukaryotes. This project aims to identify regions of the human genome that are important for gene expression during neuronal differentiation and depolarisation (i.e. neural enhancers), and to investigate their evolutionary properties. The roles of non-coding DNA in regulating the dynamic gene expression patterns underlying com ....How does the noncoding genome regulate gene expression in the human brain? The non-coding genome is recognized as a major player in orchestrating gene expression in higher eukaryotes. This project aims to identify regions of the human genome that are important for gene expression during neuronal differentiation and depolarisation (i.e. neural enhancers), and to investigate their evolutionary properties. The roles of non-coding DNA in regulating the dynamic gene expression patterns underlying complex human brain functions remains to be elucidated. By combining transcriptome quantification and bioinformatics methods, this project will close an important knowledge gap in our understanding of transcriptional regulation underlying human brain function. This will provide benefits such as the potential to influence public health policy including in cognitive functions and aging.Read moreRead less
The transcriptome dynamics that refine eukaryotic gene expression. This project aims to understand the fundamental mechanisms of gene expression control, by exploring how cells respond to acute perturbation with changes to RNA expression and processing. Unlike the static information encoded within the genome, the information encoded in its intermediary RNA, is transient, plastic and responsive to environmental and developmental cues. This project will use new technologies encompassing RNA-bioche ....The transcriptome dynamics that refine eukaryotic gene expression. This project aims to understand the fundamental mechanisms of gene expression control, by exploring how cells respond to acute perturbation with changes to RNA expression and processing. Unlike the static information encoded within the genome, the information encoded in its intermediary RNA, is transient, plastic and responsive to environmental and developmental cues. This project will use new technologies encompassing RNA-biochemistry, Next Generation Sequencing, and bioinformatics to answer long-standing questions in RNA processing. The project expects to significantly enhance our understanding of the mechanisms underpinning gene-expression control, benefitting Australia by positioning it as a world leader in the field of RNA Biology.Read moreRead less
Dissecting cell cycle regulation using programmable gene editing technology. This program aims to harness the unprecedented power of CRISPR-Cas13 gene-editing technology to develop high-throughput tools to explore the role of RNA regulation in cell cycle control. This project expects to generate new knowledge about cell division and RNA biology by utilizing this new technology and applying interdisciplinary approaches. Expected outcomes of this proposal include new research tools capable of broa ....Dissecting cell cycle regulation using programmable gene editing technology. This program aims to harness the unprecedented power of CRISPR-Cas13 gene-editing technology to develop high-throughput tools to explore the role of RNA regulation in cell cycle control. This project expects to generate new knowledge about cell division and RNA biology by utilizing this new technology and applying interdisciplinary approaches. Expected outcomes of this proposal include new research tools capable of broadly addressing biological questions across multiple disciplines (e.g. from health to food production). This project intends to provide significant benefits, such as enhanced biological knowledge, multidisciplinary training opportunities and will build Australia’s capability in this rapidly expanding field.Read moreRead less
Investigating non-canonical RNA processing in developing spermatids. RNA combines the information content of DNA and the physical properties of proteins. These features mean it's emerging as a major player for new knowledge; for answers to fundamental questions in biology, and for applications in biotechnology. This project aims to understand how non-canonical RNA processing events control gene expression. How mRNA is processed post-transcriptionally for selective storage, translation, stabilisa ....Investigating non-canonical RNA processing in developing spermatids. RNA combines the information content of DNA and the physical properties of proteins. These features mean it's emerging as a major player for new knowledge; for answers to fundamental questions in biology, and for applications in biotechnology. This project aims to understand how non-canonical RNA processing events control gene expression. How mRNA is processed post-transcriptionally for selective storage, translation, stabilisation or decay to control development. RNA-driven processes program morphogenesis and differentiation of spermatids, but via mechanisms only poorly understood. Uncovering the function of extensive cytoplasmic polyadenylation, which is essential for murine fertility, may fuel the next wave of RNA biotech applications. Read moreRead less