Engineering eukaryotic RNA-Binding proteins as molecular tools and therapeutics in cancer

RNA-binding proteins (RBPs) engage with RNA to control fundamental cellular homeostasis and perturbations in RBP–RNA networks are increasingly recognised as key contributors to cancer. With the increased understanding of RBP function in cancer onset and development, efforts are turning towards engineering RBPs with new specificities and activities to control and program cellular behaviour and develop novel therapeutic approaches.
The La-related proteins (LaRPs) are an important family of RBPs linked to cancer initiation, progression and metastasis. As other RBPs, LaRPs contain multiple domains that operate in a cooperative and/or modular fashion that enable them to associate with a variety of RNAs to execute their diverse functions. This project aims to engineer LaRPs to regulate gene expression and metabolic pathways underlying cancer phenotypes. By exploiting their modular architecture, we will mix and match RNA-binding domains to target specific RNA sequences and structures, creating customised RBPs with potential as novel anti-cancer therapeutics.