Genome-wide genetic screening with chemically mutagenized haploid embryonic stem cells

October 31st, 2016 by Josep V Forment

Nature Chemical Biology 13, 12 (2017). doi:10.1038/nchembio.2226

Authors: Josep V Forment, Mareike Herzog, Julia Coates, Tomasz Konopka, Bianca V Gapp, Sebastian M Nijman, David J Adams, Thomas M Keane & Stephen P Jackson

In model organisms, classical genetic screening via random mutagenesis provides key insights into the molecular bases of genetic interactions, helping to define synthetic lethality, synthetic viability and drug-resistance mechanisms. The limited genetic tractability of diploid mammalian cells, however, precludes this approach. Here, we demonstrate the feasibility of classical genetic screening in mammalian systems by using haploid cells, chemical mutagenesis and next-generation sequencing, providing a new tool to explore mammalian genetic interactions.

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Multidimensional chemical control of CRISPR–Cas9

October 31st, 2016 by Basudeb Maji

Nature Chemical Biology 13, 9 (2017). doi:10.1038/nchembio.2224

Authors: Basudeb Maji, Christopher L Moore, Bernd Zetsche, Sara E Volz, Feng Zhang, Matthew D Shoulders & Amit Choudhary

Cas9-based technologies have transformed genome engineering and the interrogation of genomic functions, but methods to control such technologies across numerous dimensions—including dose, time, specificity, and mutually exclusive modulation of multiple genes—are still lacking. We conferred such multidimensional controls to diverse Cas9 systems by leveraging small-molecule-regulated protein degron domains. Application of our strategy to both Cas9-mediated genome editing and transcriptional activities opens new avenues for systematic genome interrogation.

Dereplication of peptidic natural products through database search of mass spectra

October 31st, 2016 by Hosein Mohimani

Nature Chemical Biology 13, 30 (2017). doi:10.1038/nchembio.2219

Authors: Hosein Mohimani, Alexey Gurevich, Alla Mikheenko, Neha Garg, Louis-Felix Nothias, Akihiro Ninomiya, Kentaro Takada, Pieter C Dorrestein & Pavel A Pevzner

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Profiling drugs for rheumatoid arthritis that inhibit synovial fibroblast activation

October 31st, 2016 by Douglas S Jones

Nature Chemical Biology 13, 38 (2017). doi:10.1038/nchembio.2211

Authors: Douglas S Jones, Anne P Jenney, Jennifer L Swantek, John M Burke, Douglas A Lauffenburger & Peter K Sorger

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Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2

October 24th, 2016 by Xiaozhe Xiong

Nature Chemical Biology 12, 1111 (2016). doi:10.1038/nchembio.2218

Authors: Xiaozhe Xiong, Tatyana Panchenko, Shuang Yang, Shuai Zhao, Peiqiang Yan, Wenhao Zhang, Wei Xie, Yuanyuan Li, Yingming Zhao, C David Allis & Haitao Li

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Design and characterization of bivalent BET inhibitors

October 24th, 2016 by Minoru Tanaka

Nature Chemical Biology 12, 1089 (2016). doi:10.1038/nchembio.2209

Authors: Minoru Tanaka, Justin M Roberts, Hyuk-Soo Seo, Amanda Souza, Joshiawa Paulk, Thomas G Scott, Stephen L DeAngelo, Sirano Dhe-Paganon & James E Bradner

Potent and selective bivalent inhibitors of BET bromodomains

October 24th, 2016 by Michael J Waring

Nature Chemical Biology 12, 1097 (2016). doi:10.1038/nchembio.2210

Authors: Michael J Waring, Huawei Chen, Alfred A Rabow, Graeme Walker, Romel Bobby, Scott Boiko, Rob H Bradbury, Rowena Callis, Edwin Clark, Ian Dale, Danette L Daniels, Austin Dulak, Liz Flavell, Geoff Holdgate, Thomas A Jowitt, Alexey Kikhney, Mark McAlister, Jacqui Méndez, Derek Ogg, Joe Patel, Philip Petteruti, Graeme R Robb, Matthew B Robers, Sakina Saif, Natalie Stratton, Dmitri I Svergun, Wenxian Wang, David Whittaker, David M Wilson & Yi Yao

Small-molecule factor D inhibitors targeting the alternative complement pathway

October 24th, 2016 by Jürgen Maibaum

Nature Chemical Biology 12, 1105 (2016). doi:10.1038/nchembio.2208

Authors: Jürgen Maibaum, Sha-Mei Liao, Anna Vulpetti, Nils Ostermann, Stefan Randl, Simon Rüdisser, Edwige Lorthiois, Paul Erbel, Bernd Kinzel, Fabrice A Kolb, Samuel Barbieri, Julia Wagner, Corinne Durand, Kamal Fettis, Solene Dussauge, Nicola Hughes, Omar Delgado, Ulrich Hommel, Ty Gould, Aengus Mac Sweeney, Bernd Gerhartz, Frederic Cumin, Stefanie Flohr, Anna Schubart, Bruce Jaffee, Richard Harrison, Antonio Maria Risitano, Jörg Eder & Karen Anderson

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Protein dynamics: Conformational footprints

October 18th, 2016 by Buyong Ma

Nature Chemical Biology 12, 890 (2016). doi:10.1038/nchembio.2212

Authors: Buyong Ma & Ruth Nussinov

The mechanisms by which proteins evolve new functions can be slow and mysterious. Comprehensive structural analysis of enzyme variants reveal how gradual enrichments of pre-existing populations with the right productive dynamics for new functions can accomplish this aim.

Insulin signaling: At a snail’s pace

October 18th, 2016 by Stéphane Larochelle

Nature Chemical Biology 12, 889 (2016). doi:10.1038/nchembio.2221

Author: Stéphane Larochelle