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
Uncovering an evolutionary advanced mechanism of gene expression control. This project aims to uncover a new mechanism that activates gene expression in mammals, which involves unexpected connections between the core components of chromosomes and essential enzymatic machines required for the expression of genes. This project will generate new knowledge on the poorly understood process of how the extensive genomic information of multicellular organisms is selectively chosen to enable the expressi ....Uncovering an evolutionary advanced mechanism of gene expression control. This project aims to uncover a new mechanism that activates gene expression in mammals, which involves unexpected connections between the core components of chromosomes and essential enzymatic machines required for the expression of genes. This project will generate new knowledge on the poorly understood process of how the extensive genomic information of multicellular organisms is selectively chosen to enable the expression of only the required subset of genes. This will revolutionise our understanding of the mechanisms of gene control thereby shaping the field in the future. Significantly, this will allow new ways to manipulate gene expression that will impact biotechnology by providing new efficient ways to produce proteins or RNA. Read moreRead less
Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between the ....Nuclear RNA surveillance and its connection to splicing quality control. Due to the error-prone nature of RNA splicing, elaborate quality control processes ensure that only correctly spliced transcripts can leave the nucleus. It has long been known that incorrectly spliced mRNA transcripts are degraded by the nuclear RNA surveillance machinery, but how the RNA quality control machinery is connected to nuclear RNA surveillance is not known. This proposal aims to uncover the connection between these two important processes and will fill a significant gap in our understanding of how splicing quality control and nuclear RNA surveillance work. The project will also identify sequence features that trigger abortive splicing reactions and will thus help to improve the design of synthetic mRNAs.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
The role of gene isoforms in human brain development. This project aims to investigate how genes vary their products to control human brain development, by creating new methods to study gene activity in individual brain cells. Using these innovative methods, this project expects to generate fundamental new knowledge of how the human brain forms. Expected outcomes of this project include widely applicable techniques, strengthened international (UK) research collaborations and highly trained perso ....The role of gene isoforms in human brain development. This project aims to investigate how genes vary their products to control human brain development, by creating new methods to study gene activity in individual brain cells. Using these innovative methods, this project expects to generate fundamental new knowledge of how the human brain forms. Expected outcomes of this project include widely applicable techniques, strengthened international (UK) research collaborations and highly trained personnel in genomics and neuroscience. This should deliver many benefits, including a better understanding of how the brain forms, training of higher degree by research students, as well as tools and methods of benefit to the academic research and biotechnology sectors.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE210101669
Funder
Australian Research Council
Funding Amount
$430,485.00
Summary
Polycomb Group Proteins - Shaping Chromatin Architecture to Silence Genes . This project aims to address the fundamental question of how genes are switched off by studying a group of molecular off-switches, the polycomb group proteins. The project is expected to generate new knowledge in the area of gene regulation and epigenetics by combining innovative methods of structural biology and cell biology in an interdisciplinary way. The expected outcomes include a more complete picture of the molecu ....Polycomb Group Proteins - Shaping Chromatin Architecture to Silence Genes . This project aims to address the fundamental question of how genes are switched off by studying a group of molecular off-switches, the polycomb group proteins. The project is expected to generate new knowledge in the area of gene regulation and epigenetics by combining innovative methods of structural biology and cell biology in an interdisciplinary way. The expected outcomes include a more complete picture of the molecular mechanisms that regulate gene expression and the development of novel methods to image the genome. This should provide significant benefits, such as facilitated development of gene editing tools and regulatory circuits for synthetic biology, as well as novel capabilities to image the genome at high resolution Read moreRead less
Development of genetic technology for rodent population suppression. Vertebrate pests cost Australia over $1 billion each year in agricultural losses and environmental damage and novel strategies are urgently required to tackle this massive challenge. Newly proposed “gene drives”, which might rapidly spread through populations, have enormous potential for the sustained management and even eradication of pests. Through innovative application of cutting-edge genome editing approaches, this proposa ....Development of genetic technology for rodent population suppression. Vertebrate pests cost Australia over $1 billion each year in agricultural losses and environmental damage and novel strategies are urgently required to tackle this massive challenge. Newly proposed “gene drives”, which might rapidly spread through populations, have enormous potential for the sustained management and even eradication of pests. Through innovative application of cutting-edge genome editing approaches, this proposal aims to develop gene drive technology in mice as a prototypical vertebrate pest species. We will also develop cutting-edge mathematical models of rodent gene drives to identify crucial parameters for efficacious employment and investigate potential for impact on non-target populations.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
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
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