Deciphering The Role Of Atypical DNA Methylation In Neuronal Genome Regulation And Neurological Disorders
Funder
National Health and Medical Research Council
Funding Amount
$773,484.00
Summary
This research will use a combination of genomic, biochemical and functional genomics approaches to investigate the role of the atypical mCH form of DNA methylation in neuronal genome regulation and function, and provide new insights into the role of the epigenome in healthy brain function and neural pathologies.
System-level characterisation of the siphonophore, Indo-Pacific man o' war. The Indo-Pacific man o' war (bluebottle), is a cnidarian from the siphonophore order. These animals frequent Australian beaches in swarms and cause thousands of stings every year. The project proposes to profile the genome, transcriptome, epigenome, and proteome of the bluebottle to gain insight into its life cycle, its behaviour, and toxins. Expected outcomes include the generation of novel information related to bluebo ....System-level characterisation of the siphonophore, Indo-Pacific man o' war. The Indo-Pacific man o' war (bluebottle), is a cnidarian from the siphonophore order. These animals frequent Australian beaches in swarms and cause thousands of stings every year. The project proposes to profile the genome, transcriptome, epigenome, and proteome of the bluebottle to gain insight into its life cycle, its behaviour, and toxins. Expected outcomes include the generation of novel information related to bluebottle gene regulation and its toxin repertoire, which will be highly beneficial for the design of future sting treatment strategies. Given that the bluebottle is a colony made of functionally specialised polyps, this study will also provide significant novel insight into the origins and evolution of animal multicellularity.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
Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family protei ....Kruppel-like factors and the methylome. This project aims to test the hypothesis that the KLF/SP family of transcription factors work in part via dynamic interactions with methylated cytosine nucleotides in DNA. This is fundamental to their function as pioneer factors in reprograming and their ability to co-ordinate differentiation and organogenesis. Conversely, dynamic changes in methylation status engage or disengage new regulatory elements in the genome via recruitment of KLF/SP family proteins as specific effectors. This project will address a new paradigm in genetics that is likely to underpin development.Read moreRead less
The importance of DNA methylation in response to environmental changes. This project aims to investigate the importance of DNA methylation, a process whereby gene expression can be altered without changes in the DNA code, in regulating our responses to environmental challenges. It plans to do so using well-validated models of adult exposure to high fat diet or psychological stress in mice and tissue-specific (liver and brain) deletion of the major methylation enzymes. It aims to compare function ....The importance of DNA methylation in response to environmental changes. This project aims to investigate the importance of DNA methylation, a process whereby gene expression can be altered without changes in the DNA code, in regulating our responses to environmental challenges. It plans to do so using well-validated models of adult exposure to high fat diet or psychological stress in mice and tissue-specific (liver and brain) deletion of the major methylation enzymes. It aims to compare functional, gene expression and methylation status after such challenges in intact and methylase deleted animals to determine how vital this process really is. This work has major implications for our understanding of epigenetics, and the ways in which genes interact with the environment especially in times of change.Read moreRead less
The role of RNA editing by the brain-specific enzym ADAR3 in learning and memory. Higher-order cognition sets us apart from other species but how this is achieved is still under debate. The project will test the idea, strongly supported by recent genomic analyses, that subtle changes in the sequences of RNA in response to environmental stimuli underpin this extraordinary ability.
DNA exhibits new self-assembled structures due to clustered DNA methylation. This project aims to develop a technology to investigate detailed epigenetic patterns in DNA by directly interrogating the physical properties of DNA polymers in their native state. Epigenetics controls whether genes and genetic programs are turned on or off in living systems. The project will build on a recent discovery that key physical properties of native DNA polymers are strongly influenced by epigenetic patterns c ....DNA exhibits new self-assembled structures due to clustered DNA methylation. This project aims to develop a technology to investigate detailed epigenetic patterns in DNA by directly interrogating the physical properties of DNA polymers in their native state. Epigenetics controls whether genes and genetic programs are turned on or off in living systems. The project will build on a recent discovery that key physical properties of native DNA polymers are strongly influenced by epigenetic patterns created by living organisms. By fully understanding this phenomenon, this project aims to provide new tools for the study of epigenetics with broad potential applications in the life sciences, biotechnology and nanotechnology.Read moreRead less
The characterization of tiny Ribonucleic acids in animal epigenetics. Epigenetics, the inheritance of traits not encoded in deoxyribonucleic acid (DNA), is not well understood in animals. This project will investigate two classes of Ribonucleic acid (RNA) that may form part of an animal-specific epigenetic regulatory system. This study could revolutionize our understanding of animal genetics.