The role of transient DNA methylation on muscular adaptation. Regulation of gene expression is fundamental to all living organisms. This project will utilise the preliminary evidence that DNA methylation, an imprint establishing the phenotype of a specific organ, rapidly drops after an exercise bout, contradicting the dogma that DNA methylation is a locked process.
Extracellular vesicles in the inheritance of acquired traits. This project aims to examine the role of extracellular vesicles (EV) in the transfer of regulatory RNA from somatic cells to germline cells. This project suggests that somatic EVs from the epididymis transfer regulatory RNA to the sperm, and that this RNA exerts its effects in the early embryo of the next generation. This will provide significant benefits, such as a new molecular understanding of heredity that could be key to thriving ....Extracellular vesicles in the inheritance of acquired traits. This project aims to examine the role of extracellular vesicles (EV) in the transfer of regulatory RNA from somatic cells to germline cells. This project suggests that somatic EVs from the epididymis transfer regulatory RNA to the sperm, and that this RNA exerts its effects in the early embryo of the next generation. This will provide significant benefits, such as a new molecular understanding of heredity that could be key to thriving in a changing environment.Read moreRead less
The nature and extent of mammalian transgenerational epigenetic inheritance. This project aims to understand how biological information can be passed from one generation to the next without being encoded in the genes. The results of this study will inform us how this can happen, and shed light on how often it happens in mammals.
Understanding the role of endogenous siRNAs in the maintenance of genomic defenses. The inappropriate expression of retrotransposons can cause increased genomic instability. The underlying molecular pathways that control retrotransposon expression are not known. This project proposes to investigate this question at a molecular level how naturally occurring small endogenous noncoding RNAs (endo-siRNAs) enforce the epigenetic silencing of retrotransposons and examine the likely impact of endo-siRN ....Understanding the role of endogenous siRNAs in the maintenance of genomic defenses. The inappropriate expression of retrotransposons can cause increased genomic instability. The underlying molecular pathways that control retrotransposon expression are not known. This project proposes to investigate this question at a molecular level how naturally occurring small endogenous noncoding RNAs (endo-siRNAs) enforce the epigenetic silencing of retrotransposons and examine the likely impact of endo-siRNAs expression in the packaging and maintenance of retrotransposons. Understanding this fundamental question will advance the scientific knowledge of small RNA functions in our genomic defense systems. Read moreRead less
Radical change in the architecture of a nucleus: loss of typical DNA organisation systems in dinoflagellates. The genetic blueprint of all higher cells is stored in the cell nucleus, and proteins called histones provide the filing system for compactly stacking and organising the cell's DNA. One group of organisms, the dinoflagellate algae, have lost this histone system. This project will provide insight into their alternative DNA management systems.
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
Epigenetic reprogramming of development by nutritional factors in honeybee. The project aims to study the mechanism by which a specialised nutrition can change or even reverse the process of adult cell fate. The project will use a previously unexplored method of nutritional reprogramming of imaginal discs in honeybees by royal jelly and identify novel components of both the genetic and epigenetic systems that are most potent as reprogramming factors. The project seeks to improve our understandin ....Epigenetic reprogramming of development by nutritional factors in honeybee. The project aims to study the mechanism by which a specialised nutrition can change or even reverse the process of adult cell fate. The project will use a previously unexplored method of nutritional reprogramming of imaginal discs in honeybees by royal jelly and identify novel components of both the genetic and epigenetic systems that are most potent as reprogramming factors. The project seeks to improve our understanding of how epigenetic remodelling of the information content of the genome contributes to conversion of cell fate in vivo and in vitro. More broadly, the project could potentially establish the honeybee imaginal discs as a model for understanding pluripotency and environmentally controlled developmental plasticity.Read moreRead less
Charting the human epi-transcriptome. This project aims to use Oxford nanopore technologies and phage display technologies, to obtain quantitative, single-nucleotide resolution maps for any RNA modification of choice. This will allow systematic mapping of RNA modifications for which we currently lack transcriptome-wide maps, as well as investigate the roles, regulation and impact of RNA modifications in proper cellular functioning and cell differentiation. The project will provide significant be ....Charting the human epi-transcriptome. This project aims to use Oxford nanopore technologies and phage display technologies, to obtain quantitative, single-nucleotide resolution maps for any RNA modification of choice. This will allow systematic mapping of RNA modifications for which we currently lack transcriptome-wide maps, as well as investigate the roles, regulation and impact of RNA modifications in proper cellular functioning and cell differentiation. The project will provide significant benefits, such as to the economy by offering a cost-effective alternative to sequencing methods currently used to map DNA and RNA modifications.Read moreRead less
Beyond the genome: unravelling the intricacies of epigenetic regulation using the honey bee model. Epigenetic mechanisms, such as DNA methylation, provide the interface between genome and environment. Abnormalities in epigenetic regulation lead to cancer and other diseases. The project will be using the alternative phenotypes in honeybees, fertile queens and sterile workers, to understand how dietary factors control conditional gene expression by methylation
The epigenetic blueprint for T cell differentiation: a genomic view. A cardinal feature of adaptive immune cell activation is the initiation of a program of differentiation that results in acquisition and long term maintenance of lineage-speci?c effector function. This proposal aims to map and dissect genome wide molecular changes that occur at different stages of immune cell differentiation and identify key factors that regulating these changes. It is expected that distinct genomic signatures, ....The epigenetic blueprint for T cell differentiation: a genomic view. A cardinal feature of adaptive immune cell activation is the initiation of a program of differentiation that results in acquisition and long term maintenance of lineage-speci?c effector function. This proposal aims to map and dissect genome wide molecular changes that occur at different stages of immune cell differentiation and identify key factors that regulating these changes. It is expected that distinct genomic signatures, and the mechanisms indicative of effective immune cell differentiation will be identified. This proposal will provide insights into key mechanisms that result in reprogramming of immune cell function and memory and have implications for understanding general cellular differentiation.Read moreRead less