Using venoms to map critical and evolutionary conserved vulnerabilities. We have developed and applied new functional genomic approaches to study venom evolution. Using CRISPR screening, we find that unrelated venoms act on cells by exploiting the same vulnerabilities. By functionally mapping these vulnerabilities for all venom classes, we can begin to develop universal venom antidotes. Conversely, much of what we know about venom mechanisms comes from a small percentage of the biodiversity with ....Using venoms to map critical and evolutionary conserved vulnerabilities. We have developed and applied new functional genomic approaches to study venom evolution. Using CRISPR screening, we find that unrelated venoms act on cells by exploiting the same vulnerabilities. By functionally mapping these vulnerabilities for all venom classes, we can begin to develop universal venom antidotes. Conversely, much of what we know about venom mechanisms comes from a small percentage of the biodiversity within a venom, and we have developed genomic tools to study the venom “dark matter”. This work will lead to the full molecular characterisation of venom biodiversity, and new venom components will be useful for research or as novel medicines.Read moreRead less
Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput ge ....Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput genomics. The expected outcomes will overturn our current view on enhancer evolution and reposition our understanding of how enhancers are functionally encoded in the genome. The work is an important contribution to understanding cellular complexity and species evolution with wide-ranging impact in genetics.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
Cell-Sort MultiTool: a Novel Platform for Bacterial Single-Cell Analysis . This project aims to advance molecular understanding of antibiotic resistance in bacterial populations at the single-cell level, using an innovative approach integrating microfluidics, microscopy and genomics. The study of individual bacterial cell genetics is essential to provide fundamental insights into heterogeneous resistance, an important component of resistance development. Expected outcomes include a new platform ....Cell-Sort MultiTool: a Novel Platform for Bacterial Single-Cell Analysis . This project aims to advance molecular understanding of antibiotic resistance in bacterial populations at the single-cell level, using an innovative approach integrating microfluidics, microscopy and genomics. The study of individual bacterial cell genetics is essential to provide fundamental insights into heterogeneous resistance, an important component of resistance development. Expected outcomes include a new platform technology for high-throughput multiplexed screening and improved knowledge of bacterial heterogeneity, informing antibiotic usage. This interdisciplinary project should yield significant benefits in society and economy by reducing healthcare costs, boosting health for Australians and commercialising advanced technologies. 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 Epigenetics of Sex in the Dragon. Genetic codes do not directly translate to phenotypes -- environment acts through epigenetics to modify development. We use advanced molecular techniques to examine how epigenetics responds to temperature to reverse sex in our novel animal model, the dragon lizard. How does the cell sense temperature? Once the extrinsic signal is captured, how does it influence chromatin modification to release or suppress key genes in the sex differentiation pathway? Which ....The Epigenetics of Sex in the Dragon. Genetic codes do not directly translate to phenotypes -- environment acts through epigenetics to modify development. We use advanced molecular techniques to examine how epigenetics responds to temperature to reverse sex in our novel animal model, the dragon lizard. How does the cell sense temperature? Once the extrinsic signal is captured, how does it influence chromatin modification to release or suppress key genes in the sex differentiation pathway? Which sex genes are targets? Epigenetic enzymes are astonishingly conserved, providing exciting opportunities to draw from human systems to unravel novel signatures of temperature-induced sex switching in reptiles. This project will advance knowledge of developmental programming generally.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
Preventing railway suicide: An open-systems perspective. Preventing railway suicide: An open-systems perspective. This project aims to develop an automated suicide risk detection system to reduce the incidence and impact of railway suicide, which has a devastating effect on victims’ families, station staff, train drivers, emergency workers, and bystanders. This project will use open-systems theory to develop two complementary information systems for more effective detection and reporting of suic ....Preventing railway suicide: An open-systems perspective. Preventing railway suicide: An open-systems perspective. This project aims to develop an automated suicide risk detection system to reduce the incidence and impact of railway suicide, which has a devastating effect on victims’ families, station staff, train drivers, emergency workers, and bystanders. This project will use open-systems theory to develop two complementary information systems for more effective detection and reporting of suicide risk; use these systems to investigate how different situational factors interact with different combinations of service interventions to influence suicide risk; and share the findings to reduce railway suicide in Australia and overseas.Read moreRead less
Characterising inheritance patterns of whole genome DNA methylation. This project aims to characterise epigenetic diversity and inheritance patterns in whole genome sequencing data from a unique human population. The project will employ the well-characterised Norfolk Island genetic isolate, cost-effective whole genome bisulphite sequencing technologies and advanced bioinformatics pipelines and statistical models. It will involve cross-discipline collaboration between human geneticists, epigeneti ....Characterising inheritance patterns of whole genome DNA methylation. This project aims to characterise epigenetic diversity and inheritance patterns in whole genome sequencing data from a unique human population. The project will employ the well-characterised Norfolk Island genetic isolate, cost-effective whole genome bisulphite sequencing technologies and advanced bioinformatics pipelines and statistical models. It will involve cross-discipline collaboration between human geneticists, epigeneticists, statistical geneticists and bioinformaticians. This project will advance our understanding of the interaction of genetics and epigenetics and their relationship to diversity and inheritance in humans.Read moreRead less