Establishing a tractable epigenetic clock in Nasonia vitripennis

在 Nasonia vitripennis 中建立易于处理的表观遗传时钟

• 批准号: 2594855
• 金额: --
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2594855
• 关键词: Establishing; tractable; epigenetic; clock; Nasonia

Ageing is a complex process which is influenced by a myriad of genetic and environmental factors. Investigating ageing is troublesome, particularly in complex mammalian models. Ageing research is largely conducted using simple model invertebrates. There are a number of advantages to these models. However, current invertebrate models are of little use in the study of epigenetics in ageing due to their lack of DNA methylation.This project aims to establish a tractable epigenetic clock in the wasp Nasonia vitripennis, which will aid in the formation of an insect model for epigenetic ageing. Nasonia possess a functional DNA methylation system, making it an ideal candidate for this purpose. This project will use life span experiments and whole genome bisulfite sequencing (WGBS) to measure chronological and epigenetic ageing in drug altered and diapaused Nasonia. The aims of this project are: - To discover the effects of the methylation altering agent decitabine on epigenetic ageing and lifespan. - To discover if the known lifespan increasing effects of a-ketoglutarate are associated with a reduction in epigenetic ageing in insects so that we can bridge the gap between drug induced changes in epigenetic clocks and real increases in lifespan. - To discover if larval diapause early in life alters adult epigenetic ageing so that we can understand the effects of early life history on epigenetic ageing in adult insects. WGBS will be used to calculate the epigenetic clock. BS-Seq libraries will be prepared, sequenced, and aligned to the reference genome. A penalised regression will be conducted in order to identify age significant CpGs. Epigenetic age will be extracted from this model and plotted against chronological age. The establishment of a tractable insect epigenetic clock will open up a new area in biogerontology, delving into the molecular mechanisms of the malleability of the epigenetic clock and investigating the underpinning biology of epigenetic ageing.

衰老是一个复杂的过程，受到多种遗传和环境因素的影响。研究衰老是很麻烦的，特别是在复杂的哺乳动物模型中。衰老研究主要是使用简单的无脊椎动物模型进行的。这些模型有很多优点。然而，目前的无脊椎动物模型由于缺乏DNA甲基化，在衰老表观遗传学研究中用途不大。该项目旨在在黄蜂Nasonia vitripennis中建立一个易于处理的表观遗传时钟，这将有助于形成表观遗传衰老的昆虫模型。 Nasonia 拥有功能性 DNA 甲基化系统，使其成为实现此目的的理想候选者。该项目将使用寿命实验和全基因组亚硫酸氢盐测序（WGBS）来测量药物改变和滞育的 Nasonia 的时间和表观遗传衰老。该项目的目的是： - 发现甲基化改变剂地西他滨对表观遗传衰老和寿命的影响。 - 发现已知的α-酮戊二酸延长寿命的作用是否与昆虫表观遗传衰老的减少有关，以便我们能够弥合药物诱导的表观遗传时钟变化与实际寿命延长之间的差距。 - 发现幼虫生命早期的滞育是否会改变成年昆虫的表观遗传衰老，以便我们了解早期生命史对成年昆虫表观遗传衰老的影响。 WGBS 将用于计算表观遗传时钟。 BS-Seq 文库将被制备、测序并与参考基因组进行比对。将进行惩罚回归以确定年龄显着的 CpG。表观遗传年龄将从该模型中提取，并根据实际年龄绘制。易处理的昆虫表观遗传时钟的建立将开辟生物老年学的新领域，深入研究表观遗传时钟可塑性的分子机制并研究表观遗传衰老的基础生物学。