Epigenomic mechanisms regulating synaptic plasticity and cognitive ageing

真核生物信使和非编码RNA的修饰是一个控制基因表达时空模式的过程。已知腺苷的N6甲基化（m6 A/m6 am）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，可能会对可塑性和影响大脑功能的神经过程产生深远的影响。通过开发新的方法和技术，该项目将寻求确定甲基化机制和驱动突触和认知功能的途径。使用先进的显微镜和生物化学和药理学技术，我们将探索在突触位点的RNA修饰的动力学。使用一种新的转录组RNA-seq方法和人脑组织，我们将获得不同的转录谱。该项目将建立在一个尖端的研究计划，通过探索转录调控对突触过程的作用，这有助于随着年龄的增长认知能力下降。

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.