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
The transcriptome dynamics that refine eukaryotic gene expression. This project aims to understand the fundamental mechanisms of gene expression control, by exploring how cells respond to acute perturbation with changes to RNA expression and processing. Unlike the static information encoded within the genome, the information encoded in its intermediary RNA, is transient, plastic and responsive to environmental and developmental cues. This project will use new technologies encompassing RNA-bioche ....The transcriptome dynamics that refine eukaryotic gene expression. This project aims to understand the fundamental mechanisms of gene expression control, by exploring how cells respond to acute perturbation with changes to RNA expression and processing. Unlike the static information encoded within the genome, the information encoded in its intermediary RNA, is transient, plastic and responsive to environmental and developmental cues. This project will use new technologies encompassing RNA-biochemistry, Next Generation Sequencing, and bioinformatics to answer long-standing questions in RNA processing. The project expects to significantly enhance our understanding of the mechanisms underpinning gene-expression control, benefitting Australia by positioning it as a world leader in the field of RNA Biology.Read moreRead less
Investigating non-canonical RNA processing in developing spermatids. RNA combines the information content of DNA and the physical properties of proteins. These features mean it's emerging as a major player for new knowledge; for answers to fundamental questions in biology, and for applications in biotechnology. This project aims to understand how non-canonical RNA processing events control gene expression. How mRNA is processed post-transcriptionally for selective storage, translation, stabilisa ....Investigating non-canonical RNA processing in developing spermatids. RNA combines the information content of DNA and the physical properties of proteins. These features mean it's emerging as a major player for new knowledge; for answers to fundamental questions in biology, and for applications in biotechnology. This project aims to understand how non-canonical RNA processing events control gene expression. How mRNA is processed post-transcriptionally for selective storage, translation, stabilisation or decay to control development. RNA-driven processes program morphogenesis and differentiation of spermatids, but via mechanisms only poorly understood. Uncovering the function of extensive cytoplasmic polyadenylation, which is essential for murine fertility, may fuel the next wave of RNA biotech applications. 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
Targeting the genome and epigenome of the exercising skeletal muscle. This project aims is to discover epigenetic and genetic biomarkers that predict fitness changes, following exercise intervention. Individuals are remarkably variable in their responses to exercise interventions, and a large portion of these responses is attributed to genetics, and epigenetics (the effect of the environment on the expression of genes). Using controlled exercise training as a model, this project expects to disco ....Targeting the genome and epigenome of the exercising skeletal muscle. This project aims is to discover epigenetic and genetic biomarkers that predict fitness changes, following exercise intervention. Individuals are remarkably variable in their responses to exercise interventions, and a large portion of these responses is attributed to genetics, and epigenetics (the effect of the environment on the expression of genes). Using controlled exercise training as a model, this project expects to discover epigenetic and genomic markers in skeletal muscle predictive of exercise adaptations. This will contribute to the development and future delivery of targeted and personalised exercise programs for the general population. This has important implications for improving health in the Australian population.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
Can exercise slow down the epigenetic ageing clock? The aged population accounts for a significant amount of Australia’s health budget. This project aims to uncover novel molecular biomarkers that slow the ageing process and maintain good health for longer. This project aims to use innovative epigenetic analysis to study the molecular ‘clocks’ of young and old populations and to test whether exercise can slow the ageing process. This is expected to lead to a better understanding of how humans re ....Can exercise slow down the epigenetic ageing clock? The aged population accounts for a significant amount of Australia’s health budget. This project aims to uncover novel molecular biomarkers that slow the ageing process and maintain good health for longer. This project aims to use innovative epigenetic analysis to study the molecular ‘clocks’ of young and old populations and to test whether exercise can slow the ageing process. This is expected to lead to a better understanding of how humans respond to changing environments during their lifetime, and will underpin the development of evidence-based personalised health interventions to keep Australians healthier for longer.
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Epigenetic inheritance: how does it work? This project aims to determine the mechanisms responsible for the inheritance of acquired traits. Sometimes the environment can have effects on the phenotype of not only the exposed individual, but also their children and grandchildren. While it is clear that this can occur, what is not clear is the mechanism by which this happens and the frequency at which it happens. This project will use the model organism Caenorhabditis elegans, innovative new techni ....Epigenetic inheritance: how does it work? This project aims to determine the mechanisms responsible for the inheritance of acquired traits. Sometimes the environment can have effects on the phenotype of not only the exposed individual, but also their children and grandchildren. While it is clear that this can occur, what is not clear is the mechanism by which this happens and the frequency at which it happens. This project will use the model organism Caenorhabditis elegans, innovative new techniques for the discovery of low abundance RNA molecules, and fluorescence microscopy to analyse structures within the cell nucleus to determine what the molecular mechanism is by which this "transgenerational epigenetic inheritance" occurs. This will have an impact on evolutionary theory, as well as long-term consequences for the understanding of human health and disease, and the impact of a changing climate on 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