Real-time phylogenetics for food-borne outbreak surveillance. The project aims to introduce, for the first time, real-time evolutionary analysis of agricultural pathogens so that outbreaks affecting crops and the food supply can be managed precisely and rapidly. An expert team will implement a large-scale data analytics framework in user-friendly software that integrates Australian infectious disease genomics data with global data. Underpinning this work are new theory and algorithms that apply ....Real-time phylogenetics for food-borne outbreak surveillance. The project aims to introduce, for the first time, real-time evolutionary analysis of agricultural pathogens so that outbreaks affecting crops and the food supply can be managed precisely and rapidly. An expert team will implement a large-scale data analytics framework in user-friendly software that integrates Australian infectious disease genomics data with global data. Underpinning this work are new theory and algorithms that apply Sequential Monte Carlo to update phylogenetic analyses continuously as new data arrives. Expected outcomes include new knowledge of statistical algorithms for evolutionary analysis, relevant to biological disciplines beyond infectious disease; and enhanced capacity for infectious disease analysis. Read moreRead less
How novel ribosomal RNA gene repeat variants drive cellular function. The hundreds of ribosomal RNA gene repeat copies are a remarkable part of our genomes, as they encode the machinery responsible for all cellular protein synthesis and shape the structure of the nucleus. However, due to their high degree of sequence similarity, they still have not been assembled into the human genome reference. This project will resolve this impasse and furthermore uncover the functional impacts of a newly iden ....How novel ribosomal RNA gene repeat variants drive cellular function. The hundreds of ribosomal RNA gene repeat copies are a remarkable part of our genomes, as they encode the machinery responsible for all cellular protein synthesis and shape the structure of the nucleus. However, due to their high degree of sequence similarity, they still have not been assembled into the human genome reference. This project will resolve this impasse and furthermore uncover the functional impacts of a newly identified molecular diversity in the ribosomal RNA gene repeats. Outcomes include new paradigms for how the ribosomal RNA gene repeats drive protein synthesis and genome structure, and a blueprint to develop novel genomics applications for human health, biotechnology, and agriculture.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
Fine-scale resolution of genomes in natural microbial communities. This project aims to develop advanced molecular and statistical techniques to precisely resolve the genomes of microbes in the environment. Microbes inhabit every niche on the planet and are fundamental to human and animal health, agriculture, and the environment. The proposed technology will advance our understanding of environmental microbes, leading to advances in areas like climate science and biosecurity where microbes play ....Fine-scale resolution of genomes in natural microbial communities. This project aims to develop advanced molecular and statistical techniques to precisely resolve the genomes of microbes in the environment. Microbes inhabit every niche on the planet and are fundamental to human and animal health, agriculture, and the environment. The proposed technology will advance our understanding of environmental microbes, leading to advances in areas like climate science and biosecurity where microbes play a key role. It will also support the development of billion dollar industries focused on the use of beneficial microbes in agriculture, plant, animal, and human health.Read moreRead less
Whole-genome multivariate reaction norm model for complex traits. This project aims to develop a multivariate whole-genome genotype-covariate correlation and interaction model that can be applied to a wide range of existing genome-wide association study (GWAS) datasets. Genotype-covariate correlation and interaction (GCCI) are fundamental in biology but there is no standard approach to disentangle interaction from correlation in the whole-genome analyses. This project will address the key featur ....Whole-genome multivariate reaction norm model for complex traits. This project aims to develop a multivariate whole-genome genotype-covariate correlation and interaction model that can be applied to a wide range of existing genome-wide association study (GWAS) datasets. Genotype-covariate correlation and interaction (GCCI) are fundamental in biology but there is no standard approach to disentangle interaction from correlation in the whole-genome analyses. This project will address the key feature in biology, which relates to dissecting the complex mechanism of association and interaction. The proposed statistical model implemented in a context of a novel design based on multiple GWAS data sets is a paradigm shifting-tool with applications to multiple industries.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE220101210
Funder
Australian Research Council
Funding Amount
$451,634.00
Summary
Deciphering molecular genetic mechanisms underlying chromatin interactions. This project aims to generate the high confidence map of enhancer-promoter links in 61 tissues and cells through robust integration of novel machine learning tools with genomic and epigenomic datasets. Understanding which key elements in the genome may be important to fine-tune gene expression is essential for understanding biological pathways. The expected outcomes include i) New tools to robustly identify true chromati ....Deciphering molecular genetic mechanisms underlying chromatin interactions. This project aims to generate the high confidence map of enhancer-promoter links in 61 tissues and cells through robust integration of novel machine learning tools with genomic and epigenomic datasets. Understanding which key elements in the genome may be important to fine-tune gene expression is essential for understanding biological pathways. The expected outcomes include i) New tools to robustly identify true chromatin pairs; ii) Comperehensive maps of regulatory interactomes in 61 tissues & cells, which will provide a roadmap for interpreting & prioritising noncoding variants.
This should provide significant benefit to Australia's capacity for cutting-edge genomics research through fundamental understanding of gene regulation mechanism.Read moreRead less