Tight control of gene expression is critical for normal development and homeostasis. Consequently, many layers of transcriptional regulation have evolved to control RNA Polymerase II (RNAPII) mediated RNA synthesis. When transcriptional control is lost, the ensuing dysregulation of gene-expression networks invariably results in human disease, including cancer. This notion has spurred the development of novel therapies that target transcriptional complexes.  

In recent work we have combined genome-wide CRISPR-screening approaches with state-of-the-art genomics and molecular biological approaches to discover, characterise and target new transcriptional regulatory complexes (Vervoort et al. Cell 2021).  

This project will combine unbiased screening approaches, with innovative bio-sensors and CRISPR-Cas9 genome-engineering to uncover novel coding and non-coding regulators of transcription and carefully delineate their molecular role through structural, molecular and genomics technologies.