Grant: Operating Grant

Understanding the core set of human genes that are necessary for basic cellular and developmental functions is one of the central goals in biology. The study of gene essentiality in human cells is crucial for elucidating gene function and holds great potential for finding therapeutic targets for diseases such as cancer. To date this field has been constrained by technology and RNA interference has been the best available tool. But despite improvements in reagent design and analytical approaches, its utility is limited by imperfect mRNA knockdown, as well as confounding off-target effects. Technological advances in genome editing using clustered regularly interspaced short palindromic repeats CRISPR-Cas systems have set the stage for rapid advances in identifying cell-line essential genes. Pooled CRISPR-Cas approaches represent a major opportunity for systematic classification of essential and non-essential human genetic elements into functional categories and biological processes. This grant aims to expand the known set of human cancer cell essential genes in an organized and pathway-specific fashion using ultracomplex genome-scale CRISPR-Cas libraries.