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
Systems Biology Of Asthma Development In Early Childhood
Funder
National Health and Medical Research Council
Funding Amount
$763,800.00
Summary
Recent studies have established that both human genetic susceptibility and viral infections during early childhood are important drivers of asthma development. It has also been noted that asthmatics’ airways are colonized with different bacteria to non-asthmatics. In this project we will examine how genetic susceptibility and interactions between bacteria and viruses in children's airways promote the development of allergy and asthma.
Integrative Genomics And Prediction Of Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$766,820.00
Summary
Technologies that measure whole molecular systems are just beginning to reveal the complexity of living organisms and the underlying molecular networks that govern them. Cardiovascular diseases emerge out of these networks as a result of genetic and molecular perturbations. This project aims to characterize the role molecular networks play in cardiovascular disease risk as well as how they react to genetic risk factors. In doing so, it will identify potential therapeutics and personalized approa ....Technologies that measure whole molecular systems are just beginning to reveal the complexity of living organisms and the underlying molecular networks that govern them. Cardiovascular diseases emerge out of these networks as a result of genetic and molecular perturbations. This project aims to characterize the role molecular networks play in cardiovascular disease risk as well as how they react to genetic risk factors. In doing so, it will identify potential therapeutics and personalized approaches to target pathogenesis.Read moreRead less
System Biology Approaches To Uncovering Non-coding RNAs' Roles In Characterising Cancer Subtypes
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
I aim to investigate non-coding RNAs (ncRNAs)’ roles in cancer development, and how they characterise cancer subtypes. The outcomes of the proposed research are twofold: computational methods to stratify tumor subtypes and computational methods to identify groups of ncRNAs acting as drivers for each cancer subtype. The research outcomes will enable prediction of new patients’ cancer subtypes and contribute to the design of efficient treatment therapies.
Role Of RNA-binding Proteins In Cardiomyocyte Physiology
Funder
National Health and Medical Research Council
Funding Amount
$880,494.00
Summary
Interactions between ribonucleic acids and proteins are of critical importance to gene expression and may also connect it to cell metabolism in unexpected ways. We hypothesise that this is of particular importance in cardiac health and disease. We will employ the tools of proteomics and transcriptomics to characterise the topology and function of RNA-protein interaction networks in heart muscle cells, and thus contribute to the search for better treatment.
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