CRISPR_base_editing_investigation_on_the_effect_of_genomic_variation_on_protein_function_and_structure
Genetic alterations in signalling pathways, including RTK/RAS/MAPK, PI3K/AKT and P53 pathways, are common in cancer. Regulation of these signalling pathways is complex, with the activity effected by multiple factors including protein abundance, protein-protein interactions, and post-translational modifications. Using CRISPR base-editors screens we tiled across the endogenous loci of core components of the PI3K signalling pathway to identify genetic variations affecting pathway activity. Combined with structural biology approaches, we sought to understand how the identified genetic variants effected protein function. Ultimately, this information may lead to the identification of novel regulatory regions, which could be used to develop more selective compounds.