Ule and Blencowe lab

Brain RNA Regulatory Networks Laboratory

Our satellite laboratory is striving to understand the regulatory programmes that produce complex repertoires of transcripts and proteins in the nervous system, and how these programmes become dysregulated in pathological contexts.

We will then harness this knowledge to develop new gene therapy approaches for brain disorders. When genes are switched on, or ‘transcribed’, they produce messenger RNA transcripts (mRNAs) that provide the instructions for synthesising proteins, while other classes of RNAs perform important functional roles in their own right. Most human genes are initially transcribed as precursor RNAs that are subsequently processed to form a multitude of different transcript isoforms. For example, the process of alternative splicing, in which segments of precursor RNAs are differentially included in transcripts, greatly diversifies the repertoires of functional isoforms in the brain.

Transcripts do not float freely inside a cell. Instead, they are packaged by proteins that interact with RNAs. We have developed experimental and computational techniques to investigate how such protein-RNA interactions control alternative splicing as well as additional steps required for the processing and transport of RNAs in cells. We are investigating the mechanisms by which these processing steps are normally regulated and become faulty under pathological contexts in specific cell types. A particular focus of our work is to determine how the production of specific mRNA isoforms is disrupted in brain disorders. This understanding is being used to develop a new generation of context-dependent therapeutic strategies.