Where Does He Get Those Wonderful Toys? A Tour of the Functional Genomics Toolbox

The CRISPR toolbox allows functional interrogation of the genome in the service of three foundational questions: 1) What genes are involved in my phenotype of interest? 2) How does function arise from a genetic locus? 3) How do genes interact to produce a phenotype? The Genetic Perturbation Platform (GPP) at the Broad Institute engages in dozens of collaborative screening projects each year, and is also the home for >1,700 genetic screens reported in the Cancer Dependency Map (DepMap). We thus aim to continually incorporate new technologies and best practices in service of these questions, whether derived in-house or learned from the literature, quickly and at scale. Here, we will describe advances to our screening strategies across numerous CRISPR technologies, including knockout, activation, interference, and base editing.