Improving the efficiency of CRISPR gene editing in cells. Human red blood cells are well-characterised and the globin gene locus is a model system for the study of gene regulation. Gene editing technologies and delivery tools are evolving rapidly and the globin gene locus is the perfect model for gene editing optimisation. This collaboration between UNSW Sydney and CSL aims to bring together our combined expertise and new technologies to develop an optimal platform for genetic modification in a ....Improving the efficiency of CRISPR gene editing in cells. Human red blood cells are well-characterised and the globin gene locus is a model system for the study of gene regulation. Gene editing technologies and delivery tools are evolving rapidly and the globin gene locus is the perfect model for gene editing optimisation. This collaboration between UNSW Sydney and CSL aims to bring together our combined expertise and new technologies to develop an optimal platform for genetic modification in a red blood cell line. Simultaneously, this project aims to generate fundamental insights into mechanisms of human gene regulation. The technological and biological outcomes of this project will be of benefit for future gene editing applications.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
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 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
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
Discovery Early Career Researcher Award - Grant ID: DE230100271
Funder
Australian Research Council
Funding Amount
$463,618.00
Summary
Coordinating gene expression and cell size: the role of feedback regulation. This project aims to reveal how human cells coordinate the kinetics of messenger RNA (mRNA) transcript production, processing and degradation at the single-cell level. It expects to generate significant new biological knowledge of gene regulation by combining innovative interdisciplinary research methodologies in genetics, single-molecule imaging, mathematical modelling and quantitative cell biology. Expected outcomes i ....Coordinating gene expression and cell size: the role of feedback regulation. This project aims to reveal how human cells coordinate the kinetics of messenger RNA (mRNA) transcript production, processing and degradation at the single-cell level. It expects to generate significant new biological knowledge of gene regulation by combining innovative interdisciplinary research methodologies in genetics, single-molecule imaging, mathematical modelling and quantitative cell biology. Expected outcomes include enhanced training of researchers and to build Australia’s capability in the rapidly expanding fields of RNA biology and high-throughput microscopy. This should provide significant benefits for a myriad of applications including health, agriculture and veterinary sciences.Read moreRead less
Multilevel selection and the integrity of mitochondrial DNA. This project aims to investigate the evolutionary conundrum of how and why organelles remain asexual. The widespread occurrence of sexual reproduction suggests that sex is beneficial to organisms. Yet we all carry an ancient genome that never had sex, the mitochondrial genome (mtDNA). Theory predicts that mtDNA should no longer exist, because without sex it accumulates deleterious mutations and cannot accumulate beneficial ones. Yet mt ....Multilevel selection and the integrity of mitochondrial DNA. This project aims to investigate the evolutionary conundrum of how and why organelles remain asexual. The widespread occurrence of sexual reproduction suggests that sex is beneficial to organisms. Yet we all carry an ancient genome that never had sex, the mitochondrial genome (mtDNA). Theory predicts that mtDNA should no longer exist, because without sex it accumulates deleterious mutations and cannot accumulate beneficial ones. Yet mtDNA does not suffer mutational meltdown and is shown to adapt. This project will explain how, proposing that the combination of two traits, uniparental inheritance and multiple genomes per cell, make up for the lack of sex. This project expects to provide an explanation for the evolutionary question of what keeps mitochondria healthy, important as mitochondria affect ageing and health.Read moreRead less
Gene regulation by retroelement encoded natural antisense transcripts. Genetic information underpins all life on earth and is processed to make proteins, which determine the characteristics of an organism. However, only about 2% of our whole genome is made up of genes that encode proteins; the other 98% is non-coding and its function remains poorly understood. Aims and Significance: This proposal aims to utilise cutting edge genomic technologies to generate new knowledge about how the non-coding ....Gene regulation by retroelement encoded natural antisense transcripts. Genetic information underpins all life on earth and is processed to make proteins, which determine the characteristics of an organism. However, only about 2% of our whole genome is made up of genes that encode proteins; the other 98% is non-coding and its function remains poorly understood. Aims and Significance: This proposal aims to utilise cutting edge genomic technologies to generate new knowledge about how the non-coding genome regulates the expression of protein coding genes. Expected Outcomes and Benefits: This proposal will provide novel targets and methodology for gene modulation with broad applications from biology to environmental sciences.Read moreRead less
Identification of causal variants for complex traits. The aim of this project is to identify causal variants for complex traits in cattle and humans. Although most important traits in agriculture, medicine and evolution are complex traits, very few of the genetic variants affecting these traits are known and this undermines our understanding of how genetic variants affect a trait and practical uses of this knowledge. Huge datasets of individuals with genome sequence and phenotypes and new statis ....Identification of causal variants for complex traits. The aim of this project is to identify causal variants for complex traits in cattle and humans. Although most important traits in agriculture, medicine and evolution are complex traits, very few of the genetic variants affecting these traits are known and this undermines our understanding of how genetic variants affect a trait and practical uses of this knowledge. Huge datasets of individuals with genome sequence and phenotypes and new statistical methods provide the opportunity to close this gap. The outcome will be identification of many genomic variants causing variation in complex traits. This will benefit scientific understanding of complex traits and the ability to predict traits for individuals from their genome sequence.Read moreRead less