UNCOVERING REGULATORY MECHANISMS OF LIPID HOMEOSTASIS WITH CHEMICAL BIOLOGY APPROACHES
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In less than a decade, CRISPR screening has revolutionized forward genetics and cell and molecular biology. Advances in screening technologies, including sgRNA libraries, Cas9-expressing cell lines, and streamlined sequencing pipelines, have democratized pooled CRISPR screens at genome-wide scale. Initially, many such screens were survival-based, identifying essential genes in physiological or perturbed processes. With the development and application of a host of new chemical biology tools to CRISPR screening, the phenotypic space is no longer limited to live/dead selection or screening for levels of conventional fluorescent protein reporters. Further, the resolution has been increased from cell populations to single cells or even the subcellular level. Here, we highlight recent advances in pooled CRISPR screening, powered by chemical biology, that have expanded phenotypic space, resolution, scope, and scalability to enable biological hypothesis generation and discovery.