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
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
Discovery Early Career Researcher Award - Grant ID: DE200100425
Funder
Australian Research Council
Funding Amount
$409,364.00
Summary
Genetic and Molecular Consequences of Non-Random Mating in Humans. This project aims to develop and apply novel statistical methods to quantify the effects on a large number of complex traits of two forms of non-random mating in humans, that is inbreeding and assortative mating. The innovation in this proposal lies in integrating multi-level phenotypes with next-generation sequencing data collected in more than half a million study participants. Expected outcomes of this research include advance ....Genetic and Molecular Consequences of Non-Random Mating in Humans. This project aims to develop and apply novel statistical methods to quantify the effects on a large number of complex traits of two forms of non-random mating in humans, that is inbreeding and assortative mating. The innovation in this proposal lies in integrating multi-level phenotypes with next-generation sequencing data collected in more than half a million study participants. Expected outcomes of this research include advanced analytical methods to perform this integration and dissection of the biological consequences of non-random mating in humans at an unprecedented phenotypically detailed scale. The benefit of this project will be to identify new drivers of mate choice that can contribute to economic, health and social inequalities. Read moreRead less
Genetic architecture and evolution of complex traits across populations. Most human traits have a genetic component and display substantial diversity within and among populations. How natural selection changes and maintains genetic variation in human traits is a long-standing question in evolution that the proposed project aims to answer. Using innovative statistical methods and largest genomic “big” datasets ever across populations of different ancestral backgrounds, this project expects to gen ....Genetic architecture and evolution of complex traits across populations. Most human traits have a genetic component and display substantial diversity within and among populations. How natural selection changes and maintains genetic variation in human traits is a long-standing question in evolution that the proposed project aims to answer. Using innovative statistical methods and largest genomic “big” datasets ever across populations of different ancestral backgrounds, this project expects to generate new knowledge on the roles of natural selection in shaping the genetic variation in traits and identify key factors that drive the differentiation of human populations. These outcomes will significantly improve our understanding on the evolution of human traits and adaptation of populations to changing environments.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
The nature of standing genetic variation. This project aims to expand understanding of the genetic variation underlying phenotypic differences among individuals. The nature of genetic variation has broad consequences across biology, from the detection of causal genetic variants to the adaptation of natural populations. This project will take a novel experimental approach to test several long-standing assumptions about the effects of new mutations on individual traits and their joint pleiotropic ....The nature of standing genetic variation. This project aims to expand understanding of the genetic variation underlying phenotypic differences among individuals. The nature of genetic variation has broad consequences across biology, from the detection of causal genetic variants to the adaptation of natural populations. This project will take a novel experimental approach to test several long-standing assumptions about the effects of new mutations on individual traits and their joint pleiotropic effect on fitness. By expanding our understanding of how mutation, selection and drift interact, this project could provide significant improvements in our understanding of the genetic basis of phenotypes, and our ability to predict phenotypic evolution.Read moreRead less