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
An integrated molecular approach to human gene regulation. This proposal aims to reveal how the interaction of nuclear RNA and protein molecules control gene regulation in the face of cell stress. To understand how genetic variation leads to changes in the expression of genes, we need new insights into the fundamental principles underpinning complex gene regulatory systems. Building on the discovery of paraspeckles, novel gene regulatory structures, this project will yield insights into gene reg ....An integrated molecular approach to human gene regulation. This proposal aims to reveal how the interaction of nuclear RNA and protein molecules control gene regulation in the face of cell stress. To understand how genetic variation leads to changes in the expression of genes, we need new insights into the fundamental principles underpinning complex gene regulatory systems. Building on the discovery of paraspeckles, novel gene regulatory structures, this project will yield insights into gene regulation that will help fill these knowledge gaps. This will provide a more comprehensive understanding of RNA-mediated gene regulation, and will open up new research opportunities to target RNA based gene regulatory complexes.Read moreRead less
Investigating Hippo-regulated transcription at single molecule resolution. Signalling pathways operate throughout life to relay signals from the extracellular world to the cellular nucleus, to control transcription and elicit a response. This project aims to understand how the Hippo growth control pathway regulates transcription. Using a combination of biology, biophysics and computational biology, this project aims to quantify behaviour of the Hippo pathway transcription factors at sub-micron r ....Investigating Hippo-regulated transcription at single molecule resolution. Signalling pathways operate throughout life to relay signals from the extracellular world to the cellular nucleus, to control transcription and elicit a response. This project aims to understand how the Hippo growth control pathway regulates transcription. Using a combination of biology, biophysics and computational biology, this project aims to quantify behaviour of the Hippo pathway transcription factors at sub-micron resolution, and how Hippo signalling modulates their behaviour, interaction with the genome and function. We anticipate our discoveries will stimulate new research, e.g. testing of how other signaling pathways regulate transcription. Intended benefits are creation of jobs and new knowledge on fundamental principles of life.Read moreRead less
eGenomics - Next generation biomonitoring of threatened species. DNA is the molecule of life and exists everywhere in the environment as a largely untapped source of information on evolution, biodiversity, and ecosystem health. Our overriding aim is to start mining that information to benefit threatened species. Based on optimized ancient DNA methods, powerful sequencing technology, whole genome analyses, and RNA profiling, we present a novel and holistic framework for genetic biomonitoring. In ....eGenomics - Next generation biomonitoring of threatened species. DNA is the molecule of life and exists everywhere in the environment as a largely untapped source of information on evolution, biodiversity, and ecosystem health. Our overriding aim is to start mining that information to benefit threatened species. Based on optimized ancient DNA methods, powerful sequencing technology, whole genome analyses, and RNA profiling, we present a novel and holistic framework for genetic biomonitoring. In two parallel model systems we will study corals and reptiles to improve environmental detection while simultaneously obtaining information on their population health. This will foster more efficient conservation of endangered species that are of tremendous importance to our marine and terrestrial ecosystems.Read moreRead less
Regulatory roles of the RNA helicase DDX5 in male germline stem cells. This project aims to investigate the role of the RNA helicase DDX5 in regulating gene expression programs of male germline stem cells by utilising novel mouse models, stem cell culture and genome-wide analysis approaches. This project expects to generate new knowledge in the area of germline maintenance and adult stem cells using innovative in vivo and in vitro experimental systems. Expected outcomes of this project will incl ....Regulatory roles of the RNA helicase DDX5 in male germline stem cells. This project aims to investigate the role of the RNA helicase DDX5 in regulating gene expression programs of male germline stem cells by utilising novel mouse models, stem cell culture and genome-wide analysis approaches. This project expects to generate new knowledge in the area of germline maintenance and adult stem cells using innovative in vivo and in vitro experimental systems. Expected outcomes of this project will include gain of substantial insight into molecular mechanisms underlying germline stem cell function and gene regulation within the male germline. This should provide significant benefits, including advancement of reproductive science and development of systems applicable for animal germline preservation and manipulation.Read moreRead less
Regulating the composition of biomolecular condensates in living cells. Biomolecular condensation is a novel organising principle of living cells, driven by ‘unmixing’ of the cellular contents into compartments. It is observed from plants to animals and is involved in diverse processes from how cells repair DNA to how they perceive signals. This project aims to reveal how human cells control the composition of condensates, which is critical for their function. It expects to uncover new regulator ....Regulating the composition of biomolecular condensates in living cells. Biomolecular condensation is a novel organising principle of living cells, driven by ‘unmixing’ of the cellular contents into compartments. It is observed from plants to animals and is involved in diverse processes from how cells repair DNA to how they perceive signals. This project aims to reveal how human cells control the composition of condensates, which is critical for their function. It expects to uncover new regulatory principles of cellular organisation by combining methods from quantitative cell biology and statistical physics. Expected benefits include building Australia’s capability in the potentially transformational field of biomolecular condensates, which has diverse future biotechnology applications in health and agriculture.Read moreRead less
The roles and regulators of new plant cells linked to root transport. Plant genomics has moved to the single cell resolution, allowing precise investigations of previously hidden cell types and cell states that respond to environmental stress and that vary among differentially adapted plant populations. Here, we will extend our pioneering efforts that have mapped and discovered novel root cell types, to determine their salt and nutrient stress responses, and to elegantly dissect the underling ca ....The roles and regulators of new plant cells linked to root transport. Plant genomics has moved to the single cell resolution, allowing precise investigations of previously hidden cell types and cell states that respond to environmental stress and that vary among differentially adapted plant populations. Here, we will extend our pioneering efforts that have mapped and discovered novel root cell types, to determine their salt and nutrient stress responses, and to elegantly dissect the underling causal genetic variation. The unique cell markers and regulatory networks will be validated with tissue specific and transgenic tools that can work across a host of plant species to reveal adaptive cellular responses to harsh environmental conditions.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