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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2013 (arch)     Display Documents



ID: 688478.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2013 (arch)
A systematic Mammalian genetic interaction map reveals pathways underlying ricin susceptibility.
Authors:Bassik, Michael C; Kampmann, Martin; Lebbink, Robert Jan; Wang, Shuyi; Hein, Marco Y; Poser, Ina; Weibezahn, Jimena; Horlbeck, Max A; Chen, Siyuan; Mann, Matthias; Hyman, Anthony A.; Leproust, Emily M; McManus, Michael T; Weissman, Jonathan S.
Date of Publication (YYYY-MM-DD):2013
Title of Journal:Cell
Volume:152
Issue / Number:4
Start Page:909
End Page:922
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Genetic interaction (GI) maps, comprising pairwise measures of how strongly the function of one gene depends on the presence of a second, have enabled the systematic exploration of gene function in microorganisms. Here, we present a two-stage strategy to construct high-density GI maps in mammalian cells. First, we use ultracomplex pooled shRNA libraries (25 shRNAs/gene) to identify high-confidence hit genes for a given phenotype and effective shRNAs. We then construct double-shRNA libraries from these to systematically measure GIs between hits. A GI map focused on ricin susceptibility broadly recapitulates known pathways and provides many unexpected insights. These include a noncanonical role for COPI, a previously uncharacterized protein complex affecting toxin clearance, a specialized role for the ribosomal protein RPS25, and functionally distinct mammalian TRAPP complexes. The ability to rapidly generate mammalian GI maps provides a potentially transformative tool for defining gene function and designing combination therapies based on synergistic pairs.
External Publication Status:published
Document Type:Article
Communicated by:Lib
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:5201
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