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Regulation of gene expression by the maternal contribution of modified RNAs during embryonic development

胚胎发育过程中修饰 RNA 的母体贡献对基因表达的调节

基本信息

批准号：
2869579
负责人：
金额：
--
依托单位：
University of East Anglia
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2023
资助国家：
英国
起止时间：
2023 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2869579
关键词：
Regulation gene expression maternal contribution

项目摘要

Germline stem cells are essential for the survival of organisms by giving rise to the offspring. Gene expression changes within the germ cells can affect embryonic development and in some organisms such changes are transgenerationally inherited. RNA is at the centre of many gene regulatory processes. There are currently more than 150 diverse chemical modifications found on RNA and a greater number of proteins are required for their synthesis and recognition. Recent discoveries have shown that RNA modifications can be dynamically regulated and they have been implicated in embryonic development, longevity, neurological diseases and cancers in humans and in animal models.The project aims to understand how RNA modification mediated gene expression changes affect early embryonic development. The maternal (oocytes) and paternal (sperm) contribution of gene regulation can directly affect early embryonic development. In C. elegans such intergenerational gene expression changes can further lead to transgenerational phenotypes. RNA modifications are known to control the stability and dynamics of RNA deposited on oocytes and sperm which in turn could contribute to embryonic developmental and transgenerational phenotypes. The project will combine powerful C. elegans genetics with CRISPR/Cas9 mutagenesis, RNA sequencing and microscopy.

生殖系干细胞通过产生后代而对生物体的生存至关重要。生殖细胞内的基因表达变化可以影响胚胎发育，并且在某些生物体中，这种变化是转代遗传的。RNA是许多基因调控过程的中心。目前在RNA上发现了150多种不同的化学修饰，并且它们的合成和识别需要更多的蛋白质。最近的发现表明RNA修饰可以被动态调节，它们与人类和动物模型的胚胎发育、寿命、神经系统疾病和癌症有关。该项目旨在了解RNA修饰介导的基因表达变化如何影响早期胚胎发育。母亲（卵母细胞）和父亲（精子）对基因调控的贡献可以直接影响早期胚胎发育。In C.线虫这种代际间基因表达的变化可进一步导致跨代表型。已知RNA修饰控制沉积在卵母细胞和精子上的RNA的稳定性和动力学，这反过来可能有助于胚胎发育和跨代表型。该项目将联合收割机强大的C.利用CRISPR/Cas9诱变、RNA测序和显微镜技术对线虫遗传学进行了研究。