2. Academic Validation
  3. Integrating yeast chemical genomics and mammalian cell pathway analysis

Integrating yeast chemical genomics and mammalian cell pathway analysis

  • Acta Pharmacol Sin. 2019 Sep;40(9):1245-1255. doi: 10.1038/s41401-019-0231-y.
Fu-Lai Zhou  # 1 2,  Sheena C Li  # 3,  Yue Zhu 1 2,  Wan-Jing Guo 1 2,  Li-Jun Shao 1 2,  Justin Nelson 4,  Scott Simpkins 4,  De-Hua Yang 1,  Qing Liu 1,  Yoko Yashiroda 3,  Jin-Biao Xu 5,  Yao-Yue Fan 5,  Jian-Min Yue 5,  Minoru Yoshida 3 6 7,  Tian Xia 8,  Chad L Myers 9,  Charles Boone 10 11,  Ming-Wei Wang 12 13
Affiliations

Affiliations

  • 1 The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, 201203, China.
  • 2 University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 3 RIKEN Center for Sustainable Resource Science, Wako, Saitama, 3510198, Japan.
  • 4 Bioinformatics and Computational Biology Program, University of Minnesota-Twin Cities, Minneapolis, Minnesota, 55455, USA.
  • 5 The State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 6 Department of Biology, The University of Tokyo, Bunkyo-ku, Tokyo, 1138657, Japan.
  • 7 Collaborative Research for Innovative Microbiology, The University of Tokyo, Bunkyo-ku, Tokyo, 1138657, Japan.
  • 8 Department of Electronics and Information Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China.
  • 9 Bioinformatics and Computational Biology Program, University of Minnesota-Twin Cities, Minneapolis, Minnesota, 55455, USA. [email protected].
  • 10 RIKEN Center for Sustainable Resource Science, Wako, Saitama, 3510198, Japan. [email protected].
  • 11 Donnelly Centre and Department of Molecular Genetics, University of Toronto, Ontario, M5S 3E1, Canada. [email protected].
  • 12 The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, 201203, China. [email protected].
  • 13 University of Chinese Academy of Sciences, Beijing, 100049, China. [email protected].
  • # Contributed equally.
PMID: 31138898 DOI: 10.1038/s41401-019-0231-y
Abstract

Chemical genomics has been applied extensively to evaluate small molecules that modulate biological processes in Saccharomyces cerevisiae. Here, we use yeast as a surrogate system for studying compounds that are active against metazoan targets. Large-scale chemical-genetic profiling of thousands of synthetic and natural compounds from the Chinese National Compound Library identified those with high-confidence bioprocess target predictions. To discover compounds that have the potential to function like therapeutic agents with known targets, we also analyzed a reference library of approved drugs. Previously uncharacterized compounds with chemical-genetic profiles resembling existing drugs that modulate Autophagy and Wnt/β-catenin signal transduction were further examined in mammalian cells, and new modulators with specific modes of action were validated. This analysis exploits yeast as a general platform for predicting compound bioactivity in mammalian cells.

Keywords

Wnt/β-catenin signaling pathway; autophagy; chemical genomics; tubulin cytoskeleton assembly; yeast.

Figures
Products