How does an essential histone variant effect changes in gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are not clearly known. It is well established that gene expression patterns are determined in part by the molecular signals transmitted by variation in the proteins that package eukaryotic DNA. Our aim is to understand new aspects of these mechanisms that revolve around how our DNA is packaged. This foundational knowl ....How does an essential histone variant effect changes in gene expression? The mechanisms that determine how genes are switched on and off in different tissues and at different times are not clearly known. It is well established that gene expression patterns are determined in part by the molecular signals transmitted by variation in the proteins that package eukaryotic DNA. Our aim is to understand new aspects of these mechanisms that revolve around how our DNA is packaged. This foundational knowledge will deepen our understanding of gene regulation in all complex organisms and will inform future efforts to rationally modulate gene expression patterns in agriculture, research and other important areas.Read moreRead less
Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project ....Transcription factors find their targets by reading the epigenetic code. This project aims to elucidate how transcription factors, proteins that regulate gene expression, find their target genes. The hypothesis is that non-DNA binding domains play an essential role in this process. This project expects to transform our understanding of transcription factor families, and how factors in families with the same DNA-binding domain manage to regulate different genes. Expected outcomes of this project include revealing how accessory proteins help transcription factors identify their targets in the genome by reading epigenetic marks. This should provide significant benefits including improved design of artificial transcription factors to up- or down-regulate specific genes in research and agriculture.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
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