The molecular mechanism of action of bacterial epigenetic regulators. This project aims to determine the mechanisms of action of a class of bacterial epigenetic regulators. Many bacteria exhibit phase variable expression of genes (random, high frequency on/off switching of expression), typically due to simple DNA repeats within the gene(s) that encode them. Many bacterial species contain phase variable DNA methyltransferases that regulate epigenetics and control expression of distinct sets of pr ....The molecular mechanism of action of bacterial epigenetic regulators. This project aims to determine the mechanisms of action of a class of bacterial epigenetic regulators. Many bacteria exhibit phase variable expression of genes (random, high frequency on/off switching of expression), typically due to simple DNA repeats within the gene(s) that encode them. Many bacterial species contain phase variable DNA methyltransferases that regulate epigenetics and control expression of distinct sets of proteins (phasevarions) via variable methylation of the genome. The precise mechanism of action of these regulators is unknown. Characterisation of these systems will provide better understanding of bacterial gene regulation and adaptation, which will inform biotechnology and vaccine development and could contribute to economic and health advancements.Read moreRead less
How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, ....How enhancers regulate T cell differentiation and function. This project aims to identify the molecular mechanisms that regulate the activity of transcriptional enhancers needed for effective immune cell differentiation. Adaptive immune cell activation starts a programme of differentiation that acquires and maintains lineage-specific effector function. Using a multidisciplinary approach including cellular and chromatin biology, advanced bioinformatics, targeted genome editing and nanotechnology, this project expects to provide insights into non-coding regulatory element reprogramming and control of immune cell function and memory with implications for understanding general cellular differentiation.Read moreRead less
Cell-type specific profiling of nascent RNA in the brain during learning. This project aims to understand cell-type specific, fast-acting, and dynamic patterns of RNA expression that arise during learning and contribute to the formation of memory. Activity-induced gene expression is central to neural plasticity, learning and memory. The project will apply a new approach, which tags RNA inside living cells. The findings will be broadly applicable and create new opportunities for understanding the ....Cell-type specific profiling of nascent RNA in the brain during learning. This project aims to understand cell-type specific, fast-acting, and dynamic patterns of RNA expression that arise during learning and contribute to the formation of memory. Activity-induced gene expression is central to neural plasticity, learning and memory. The project will apply a new approach, which tags RNA inside living cells. The findings will be broadly applicable and create new opportunities for understanding the true nature of brain adaptation.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.
Phenotypic profiling from DNA using genetic and epigenetic information. The project intends to quantify how much information about a person can be inferred from a DNA sample. A DNA sample contains epigenomic information additional to the genome sequence. This information can reflect age and the past and present lifestyle of the individual whose sample it is. The project aims to quantify the accuracy of lifestyle and phenotypic prediction from DNA. Existing genome-wide genotype and methylation ar ....Phenotypic profiling from DNA using genetic and epigenetic information. The project intends to quantify how much information about a person can be inferred from a DNA sample. A DNA sample contains epigenomic information additional to the genome sequence. This information can reflect age and the past and present lifestyle of the individual whose sample it is. The project aims to quantify the accuracy of lifestyle and phenotypic prediction from DNA. Existing genome-wide genotype and methylation array data from thousands of blood samples from human subjects will be statistically analysed to develop and validate predictors for chronological age, smoking, caffeine use, pesticide exposure, diet and body mass index. Potential applications of epigenomic prediction are widespread, ranging from forensics to ecology.Read moreRead less
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.
Systemic gene silencing in Arabidopsis, and relevance to plant biology. Gene silencing is a highly conserved process in plants and animals. It is of fundamental importance to gene regulation, virus defence, genome response to environment, and genome evolution. Remarkably, when gene silencing is triggered in plants it can spread throughout the organism. The aim of this project is to define the mechanism of intercellular movement of gene silencing in plants, and its relevance to plant growth and d ....Systemic gene silencing in Arabidopsis, and relevance to plant biology. Gene silencing is a highly conserved process in plants and animals. It is of fundamental importance to gene regulation, virus defence, genome response to environment, and genome evolution. Remarkably, when gene silencing is triggered in plants it can spread throughout the organism. The aim of this project is to define the mechanism of intercellular movement of gene silencing in plants, and its relevance to plant growth and defence against pathogens. Expected outcomes include increased understanding of intercellular genetic signalling in plants and its role in plant growth and disease resistance. The findings may also shed new light on mechanisms of gene silencing in animals.Read moreRead less