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

近交系小鼠中可变甲基化转座元件的遗传学

基本信息

批准号：
1795629
负责人：
金额：
--
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1795629
关键词：
genetics variably methylated transposable elements

项目摘要

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.

布景主题：这个博士项目的总体目标是研究母体肥胖对发育中胚胎的表观基因组和转录组的影响。母亲肥胖与后代健康状况不佳有关，尽管这种情况发生的过程尚不清楚。我假设，与对照胚胎相比，暴露于母体高脂肪饮食的胚胎的转录组和表观基因组（组蛋白修饰和/或甲基化组）将发生显着变化。这些变化可能会持续到成年。为了探讨这些问题，我将使用高脂饮食诱导的肥胖母鼠模型。第一个实验将集中在e6.5胚胎，这些胚胎将通过自然定时交配以及暴露于饮食的雌性与维持饮食的雄性的IVF产生。将收集的胚胎解剖成胎盘和胚胎本身：从这些中，将生成ChIP-seq、BS-seq和RNA-seq文库，并分析来自暴露于普通饮食和暴露于高脂肪饮食的母体的胚胎之间的差异。在此之后，博士项目的目标可能会根据我得到的结果，我希望解决的生物学问题以及各种技术的发展阶段而改变。我可能追求的一个方向将是确定在胚胎发育过程中这些表观遗传变化出现的时间点以及负责的机制。另一个方向将是在基因组调控的背景下研究这些表观遗传变化的功能意义和相关性。