Epigenomic mechanisms regulating synaptic plasticity and cognitive ageing

调节突触可塑性和认知衰老的表观基因组机制

• 批准号: 2594633
• 金额: --
• 依托单位: University of Nottingham
• 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-2594633
• 关键词: Epigenomic; mechanisms; regulating; synaptic; plasticity

Modification of eukaryote messenger and noncoding RNAs is a process which governs spatio-temporal patterns of gene expression. N6 methylation of adenosines (m6A/m6am) is known to affect RNA stability, translation status, splicing and subcellular mRNA localisation. Failure to regulate the transcriptome at the right place and time, potentially has a profound effect on plasticity and neural processes which influence brain function over the lifespan. Through the development of novel approaches and techniques, the project will seek to determine the methylation machinery and pathways driving synaptic and cognitive function. Using advanced microscopy and biochemical and pharmacological techniques, we will explore the dynamics of RNA modification at synaptic sites. Using a new transcriptomic RNA-seq method and human brain tissue, we will characterise distinct transcript profiles. This project will build upon a cutting-edge programme of research by exploring the role of transcriptomic regulation on synaptic processes which contribute to cognitive decline with age.

真核生物信使和非编码 RNA 的修饰是控制基因表达时空模式的过程。已知腺苷的 N6 甲基化 (m6A/m6am) 会影响 RNA 稳定性、翻译状态、剪接和亚细胞 mRNA 定位。未能在正确的地点和时间调节转录组可能会对可塑性和神经过程产生深远的影响，从而影响整个生命周期的大脑功能。通过开发新的方法和技术，该项目将寻求确定驱动突触和认知功能的甲基化机制和途径。利用先进的显微镜以及生化和药理学技术，我们将探索突触位点 RNA 修饰的动态。使用新的转录组 RNA-seq 方法和人脑组织，我们将表征不同的转录谱。该项目将建立在一项前沿研究计划的基础上，探索转录组调控对突触过程的作用，突触过程会导致认知能力随着年龄的增长而下降。