Multi-functional genome-wide CRISPR system for high throughput genotype–phenotype mapping

Lian, Jiazhang; Schultz, Carl; Cao, Mingfeng; HamediRad, Mohammad; Zhao, Huimin

doi:10.1038/s41467-019-13621-4

Title: Multi-functional genome-wide CRISPR system for high throughput genotype–phenotype mapping

Journal Article · Thu Dec 19 00:00:00 UTC 2019 · Nature Communications

DOI: https://doi.org/10.1038/s41467-019-13621-4 · OSTI ID:1619764

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; Cao, Mingfeng;

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Abstract Genome-scale engineering is an indispensable tool to understand genome functions due to our limited knowledge of cellular networks. Unfortunately, most existing methods for genome-wide genotype–phenotype mapping are limited to a single mode of genomic alteration, i.e. overexpression, repression, or deletion. Here we report a multi-functional genome-wide CRISPR (MAGIC) system to precisely control the expression level of defined genes to desired levels throughout the whole genome. By combining the tri-functional CRISPR system and array-synthesized oligo pools, MAGIC is used to create, to the best of our knowledge, one of the most comprehensive and diversified genomic libraries in yeast ever reported. The power of MAGIC is demonstrated by the identification of previously uncharacterized genetic determinants of complex phenotypes, particularly those having synergistic interactions when perturbed to different expression levels. MAGIC represents a powerful synthetic biology tool to investigate fundamental biological questions as well as engineer complex phenotypes for biotechnological applications.

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Research Organization:: Univ. of Illinois at Urbana-Champaign, Urbana, IL (United States)

Sponsoring Organization:: USDOE; USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23). Biological Systems Science Division

Grant/Contract Number:: SC0018260

OSTI ID:: 1619764

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 10; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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