Application of CRISPR-Cas9 Based Genome-Wide Screening Approaches to Study Cellular Signalling Mechanisms

Abstract

The cellular signalling process is a highly complex mechanism, involving multiple players, which together orchestrate the cell's response to environmental changes and perturbations. Given the multitude of genes that participate in the process of cellular signalling, its study in a genome-wide manner has proven challenging. Recent advances in gene editing technologies, including clustered regularly-interspaced short palindromic repeats/Cas9 (CRISPR/Cas9) approaches, have opened new opportunities to investigate global regulatory signalling programs of cells in an unbiased manner. In this review, we focus on how the application of pooled genetic screening approaches using the CRISPR/Cas9 system has contributed to a systematic understanding of cellular signalling processes in normal and disease contexts.

Keywords: CRISPR/Cas9; cellular signalling; genome-wide screens.

Figure 1

Overview of major cellular signalling process and pathways. Cell surface receptors receive instructional signals from the environment through interaction with extracellular ligands. This signal is then transduced across the plasma membrane where intracellular second messengers amplify and relay the information to elicit cellular responses. Ligands that utilise common signalling pathways and associated transcription factors are depicted in the left panel (an excellent resource for an overview of cellular signalling pathways can be found at the Internet resource: Cell Signaling Pathways by Michael Berridge [12]).

Figure 2

Summary of the screening approaches described in this review. Specific features of each approach are indicated in blue (strengths) and red (limitations) boxes.