Epigenomic mechanisms regulating synaptic plasticity and cognitive ageing

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.