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
Uncovering microRNA decay regulation in mammalian cells. MicroRNAs (miRNAs) constitute a novel mechanism used by cells to regulate gene expression, however, very little is known about the mechanisms affecting miRNA accumulation. Characterisation of the kinetics of miRNA turnover is of paramount importance to establish the reliability of miRNAs as novel biomarkers. This project aims to characterise miRNA stability in mammalian cells, investigate mechanisms of turnover and establish their importan ....Uncovering microRNA decay regulation in mammalian cells. MicroRNAs (miRNAs) constitute a novel mechanism used by cells to regulate gene expression, however, very little is known about the mechanisms affecting miRNA accumulation. Characterisation of the kinetics of miRNA turnover is of paramount importance to establish the reliability of miRNAs as novel biomarkers. This project aims to characterise miRNA stability in mammalian cells, investigate mechanisms of turnover and establish their importance on the regulatory function of miRNAs. Such information is critical in the future development of targeted therapeutics.Read moreRead less
Developing bioinformatics methods for single cell transcriptomics. This project aims to develop novel bioinformatics methods for single cell transcriptomic data that seek to model variability in cell populations. The project expects to generate new approaches using Bayesian statistics that will act as high-end enablers of discovery in transcriptional regulatory processes. Through an interdisciplinary combination of experimental and computational research, insights into fundamental biological pro ....Developing bioinformatics methods for single cell transcriptomics. This project aims to develop novel bioinformatics methods for single cell transcriptomic data that seek to model variability in cell populations. The project expects to generate new approaches using Bayesian statistics that will act as high-end enablers of discovery in transcriptional regulatory processes. Through an interdisciplinary combination of experimental and computational research, insights into fundamental biological processes will be elucidated, specifically the robustness of cellular systems. Expected outcomes include a suite of novel tools that will push the boundaries of current bioinformatics solutions with potential to deliver significant benefits to every domain of biological science, particularly tissue engineering and synthetic biology.Read moreRead less
Transcription factor – enhancer – promoter based regulatory networks. This project aims to develop new understanding on how multicellular organisms (including humans) develop, and how mutations in distant regions of the genome can affect human traits. The way the human genome is interpreted by the cellular machinery is still a mystery. We have a reference sequence and know where the majority of coding genes are, but we are far from understanding how the genome is regulated to generate the divers ....Transcription factor – enhancer – promoter based regulatory networks. This project aims to develop new understanding on how multicellular organisms (including humans) develop, and how mutations in distant regions of the genome can affect human traits. The way the human genome is interpreted by the cellular machinery is still a mystery. We have a reference sequence and know where the majority of coding genes are, but we are far from understanding how the genome is regulated to generate the diversity of cell types in our bodies. Enhancer regions interact with proximal promoters to regulate gene expression level and tissue-specificity. This project aims to develop transcriptional regulatory network models using high throughput chromatin interaction data and expression perturbation to link promoter and enhancers genome-wide.Read moreRead less
Commensal benefits: genomic basis for suppressing plant pathogens with Pseudomonas biocontrol species. Food security is an issue of mounting significance due to unpredictable climate trends and increasing global population growth. A feature of paramount importance to reliable crop production is the capacity to control plant diseases. This project investigates natural plant colonising bacteria as a tool for protecting plants from disease.
Computational systems biology: understanding mammalian cell fates using genome-scale network models. Mutations can disrupt the cellular networks that control normal development, causing cells to develop abnormally including in ways that lead to cancer. The project will analyse genome sequences from more than 700 pancreatic cancers and matched controls to precisely map the causative trail from mutations to disrupted networks to altered cell development.
Transcriptional regulation by microRNAs. This project aims to better understand microRNAs, which are of central importance to how genes are regulated. Despite recent data indicating microRNAs may also play more extensive and diverse roles as nuclear regulators of gene transcription, research has been restricted to their well known mechanism of action in the cytoplasm where they post transcriptionally silence genes. This project will investigate the potential for microRNAs to regulate transcripti ....Transcriptional regulation by microRNAs. This project aims to better understand microRNAs, which are of central importance to how genes are regulated. Despite recent data indicating microRNAs may also play more extensive and diverse roles as nuclear regulators of gene transcription, research has been restricted to their well known mechanism of action in the cytoplasm where they post transcriptionally silence genes. This project will investigate the potential for microRNAs to regulate transcription on a genome-wide scale and will thereby reveal the full extent of mechanisms by which these important genetic switches control gene expression networks the characteristics of cells. This is of fundamental significance to our understanding of gene regulation.Read moreRead less
Understanding the robustness and plasticity of metabolite concentrations. This project aims to further the understanding of how organisms mitigate the effects of changing environment by altering metabolite concentrations, important for food quality, energetics, and health. Through this understanding, the project provides the potential to precisely tailor metabolic intervention strategies, highly beneficial for applied sciences. The expected outcome of the project is a suite of computational appr ....Understanding the robustness and plasticity of metabolite concentrations. This project aims to further the understanding of how organisms mitigate the effects of changing environment by altering metabolite concentrations, important for food quality, energetics, and health. Through this understanding, the project provides the potential to precisely tailor metabolic intervention strategies, highly beneficial for applied sciences. The expected outcome of the project is a suite of computational approaches that allow for integration of large-scale data with networks to predict metabolite concentration ranges. This will provide significant benefit with the aim of maintaining outstanding research in Australia, and has clear potential for improved human health and enhanced food quality via metabolic reprogramming.Read moreRead less