The genetics of variably-methylated transposable elements in inbred strains of mice

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Theme: Bioscience for HealthThe overall aim of this PhD project is to investigate the effect of maternal obesity on the epigenome and transcriptome of the developing embryo. Maternal obesity has been associated with poor health outcomes in offspring although the process by which this occurs is not well understood. I hypothesise that embryos exposed to a maternal high-fat diet will have significant changes to their transcriptome and epigenome (histone modifications and/or methylome) compared to control embryos. These changes may persist into adult life. To probe these questions, I will use a high-fat diet induced obese maternal mouse model. The first experiments will focus on e6.5 embryos which will be generated by natural timed matings as well as IVF of the diet-exposed females with chow-diet maintained males. The collected embryos will be dissected into the placenta and embryo proper: from these, ChIP- seq, BS-seq and RNA-seq libraries will be generated and analysed for differences between embryos derived from chow-diet exposed and high-fat diet exposed mothers. Following this, the aims of the PhD project may shift depending on the results I get, the biological question I wish to address and the stage of development of various technologies. One direction I may pursue will be establishing at what time point during embryonic development these epigenetic changes arise and the mechanism responsible. An alternative direction would be to characterise the functional implication and relevance of these epigenetic changes in the context of genomic regulation.