Epigenetic regulation of genomic stability and inheritance. Sperm mediate inheritance by transmitting DNA and associated chemical (epigenetic) modifications to offspring. We hypothesise that epigenetic modifications protect DNA from mutations during sperm formation. Using innovative models, our interdisciplinary team will determine whether loss of specific epigenetic modifications permits mutations in sperm and whether these mutations are transmitted to offspring. Our work will contribute to und ....Epigenetic regulation of genomic stability and inheritance. Sperm mediate inheritance by transmitting DNA and associated chemical (epigenetic) modifications to offspring. We hypothesise that epigenetic modifications protect DNA from mutations during sperm formation. Using innovative models, our interdisciplinary team will determine whether loss of specific epigenetic modifications permits mutations in sperm and whether these mutations are transmitted to offspring. Our work will contribute to understanding how new mutations arise in sperm and potentially affect offspring phenotype, adaptation and evolution. As chemicals, drugs and diet can affect epigenetic function, our studies will also contribute to determining how epigenetic inheritance affects environmental, agricultural and healthcare outcomes.Read moreRead less
Understanding co-activator function in transcriptional regulation. A change in gene expression underpins all cell fate decisions yet there is scant knowledge about how transcription factors (TF), the master regulators of transcription, specifically interact with some, but not all, transcription cofactors to nuance gene expression. Aims: Using innovative molecular technologies we will identify and characterise the shared and unique relationships between TF and cofactors. Significance: This study ....Understanding co-activator function in transcriptional regulation. A change in gene expression underpins all cell fate decisions yet there is scant knowledge about how transcription factors (TF), the master regulators of transcription, specifically interact with some, but not all, transcription cofactors to nuance gene expression. Aims: Using innovative molecular technologies we will identify and characterise the shared and unique relationships between TF and cofactors. Significance: This study is important to every biological process in plants and animals driven by a change in gene expression. Expected Outcomes: This study will increase our biological knowledge in transcription control. Benefit: The knowledge gained has future applications in genomics and broad implications for biotechnology and industry.Read moreRead less
The T cell genome in 3D: linking chromatin structure to cellular function. Adaptive immune cell activation results in the acquisition and long term maintenance of specific cellular function that enables efficient immune control of infections. Using advanced cellular and genomic approaches, combined with high-resolution microscopy and cutting edge computational biology, this proposal aims to address major gaps in our knowledge about how alterations in genomic 3D architecture and targeted biochemi ....The T cell genome in 3D: linking chromatin structure to cellular function. Adaptive immune cell activation results in the acquisition and long term maintenance of specific cellular function that enables efficient immune control of infections. Using advanced cellular and genomic approaches, combined with high-resolution microscopy and cutting edge computational biology, this proposal aims to address major gaps in our knowledge about how alterations in genomic 3D architecture and targeted biochemical modifications impact cell specific gene nuclear positioning and how this regulates changes in gene expression associated with immune cell activation. An outcome will be identification of novel molecular mechanisms that will have broad applicability across cellular biology, and provide novel targets for drug development.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
Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations ....Visualising chromatin changes in 3 dimensions: super to ultra resolution. Packaging of genomic information into the nucleus of a cell necessitates the formation of tightly compacted and highly organized genomic structures within the nucleus, a configuration that is inherently repressive for gene transcription. Hence, mechanisms that alter the spatial organisation of DNA are critical to enable a variety of genome functions, including DNA transcription. This proposal will utilise novel adaptations of super resolution microscopy to visualise in 3 dimensions how changes in chromatin modifications impact genome spatial organisation within the nucleus, and how this then links to cellular differentiation. This will provide a picture of how spatial organisation within the nucleus supports general cell differentiation.
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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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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
Histone H3.3-dependent transcriptional control and B cell differentiation. This project aims to investigate the fundamental way cells assemble transcriptional machinery to turn on genes and retain transcriptional memory. This project expects to generate new knowledge in the areas of both chromatin biology and immunology, using interdisciplinary approaches. Expected outcomes of this project include an enhanced capacity, through institutional and international collaborations, to determine whether ....Histone H3.3-dependent transcriptional control and B cell differentiation. This project aims to investigate the fundamental way cells assemble transcriptional machinery to turn on genes and retain transcriptional memory. This project expects to generate new knowledge in the areas of both chromatin biology and immunology, using interdisciplinary approaches. Expected outcomes of this project include an enhanced capacity, through institutional and international collaborations, to determine whether the rapid transcription and function characteristic of immune memory in response to stimuli is due to histone H3 variant and its associated nuclear bodies. This should provide significant benefits, such as understanding epigenetic mechanisms that underlie transcription initiation and maintenance across many species.Read moreRead less
Genetic networks regulating gene silencing by intronic repeat expansions . Changes in the copy number of DNA repeats are associated with phenotypic variations in several species. Expansions of DNA repeats underlie several human genetic diseases, including Friedreich’s ataxia. The molecular mechanisms that mediate these genetic abnormalities are currently unclear. This project aims to identify the novel genetic pathways and mechanisms mediating these genetic disorders. Using a plant model in an .... Genetic networks regulating gene silencing by intronic repeat expansions . Changes in the copy number of DNA repeats are associated with phenotypic variations in several species. Expansions of DNA repeats underlie several human genetic diseases, including Friedreich’s ataxia. The molecular mechanisms that mediate these genetic abnormalities are currently unclear. This project aims to identify the novel genetic pathways and mechanisms mediating these genetic disorders. Using a plant model in an innovative way this project will discover novel genes, uncover fundamental molecular mechanisms and reveal the genetic networks that govern gene silencing caused by triplet repeat expansions. This project, in addition to revealing fundamental biological mechanisms, will also have implications for human disease.
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Genetic, Cellular and Molecular Analysis of Cardiac Ventricular Septation. The project aims to define the blueprint for ventricular septation in the mammalian heart – how, during heart development, a single ventricle becomes divided in two by a muscular wall, thus creating left and right pumps and electrical circuits serving the body and lung circulations separately. A proprietary mouse genetic model was created and will be used to probe the cellular and molecular mechanisms of septation using n ....Genetic, Cellular and Molecular Analysis of Cardiac Ventricular Septation. The project aims to define the blueprint for ventricular septation in the mammalian heart – how, during heart development, a single ventricle becomes divided in two by a muscular wall, thus creating left and right pumps and electrical circuits serving the body and lung circulations separately. A proprietary mouse genetic model was created and will be used to probe the cellular and molecular mechanisms of septation using new technologies able to resolve biology at a single-cell level. Outcomes may include new knowledge on heart development and evolution, including how the cardiac electrical system is formed, and how cell boundaries and tissue complexity are generated. The project may advance new technologies and create new data resources.Read moreRead less