2019 Fiscal Year Annual Research Report
A chemical genomics approach for understanding chemical communication
| Project Area | Frontier research of chemical communications |
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| Project/Area Number |
17H06411
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
BOONE CHARLES 国立研究開発法人理化学研究所, 環境資源科学研究センター, チームリーダー (70601342)
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| Co-Investigator(Kenkyū-buntansha) |
八代田 陽子 国立研究開発法人理化学研究所, 環境資源科学研究センター, 専任研究員 (60360658)
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| Project Period (FY) |
2017-06-30 – 2022-03-31
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| Keywords | chemical genomics / yeast / chemical communication |
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| Outline of Annual Research Achievements |
We established the chemical genomics (CG) platform; CG analysis using the whole genome (WG), HET/TS and MoBY libraries and drug-resistant mutants), for which we have been writing a manuscript.
Target identification experiments have been carried out for bioactive compounds provided from the groups A01 (Dr. Hideaki Kakeya and Dr. Hirokazu Kawagishi) and A02 (Dr. Ryuichi Sakai). We screened WG/HET/TS/MoBY libraries for the collaborators’ compounds and found several candidate target genes from CG analyses using computational tools including CG-TARGET developed in collaboration with University of Minnesota. To validate drug-target interactions, we executed morphological observation upon treatment with the compounds and isolation of drug resistant mutants.
To further examine novel drug-target interactions, we employed a new set of ~10,000 compounds from the RIKEN NPDepo library, which consisted of natural products and their derivatives. First, we assessed bioactivity using the budding yeast Saccharomyces cerevisiae and identified ~380 bioactive compounds that showed >30% growth inhibition at 10 microG/mL. Next we prepared the samples for CG analysis using the HET/TS libraries. We treated the HET/TS libraries with the compounds at multiple concentrations ranging from 10 to 0.25 microG/mL and extracted DNA from the library cells. The DNA samples will be subjected to next generation sequencing for target identification.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
We accomplished the mission as planned. We are currently preparing a manuscript for our chemical genomic pipeline.
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| Strategy for Future Research Activity |
We will carry out CG analysis for target identification of ~380 newly screened bioactive compounds. We will continue to validate target identification of the Group A01/A02 collaborators’ compounds. We will start to develop a CG analysis method using human cells in collaboration with University of Toronto.
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| Remarks |
（1）"Drugs Made in Nature: Donnelly Researchers Team up with Japanese Scientists to Mine Microbes for New Therapeutics", Donnelly Centre News（作成：トロント大学）
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[Journal Article] Integrating yeast chemical genomics and mammalian cell pathway analysis2019
Author(s)
Zhou, FL., Li, SC., Zhu, Y., Guo, WJ., Shao, LJ., Nelson, J., Simpkins, S., Yang, DH., Liu, Q., Yashiroda, Y., Xu, JB., Fan, YY., Yue, JM., Yoshida, M., Xia, T., Myers, CL., Boone, C., Wang, MW.
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Journal Title
Acta Pharmacol. Sin.
Volume: 40
Pages: 1245, 1255
DOI
Peer Reviewed / Int'l Joint Research
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[Presentation] An Integrated Chemical Genomic Approach for Target Identification2019
Author(s)
Yoko Yashiroda, Sheena Li, Urvi Bhojoo, Mami Yoshimura, Hiromi Kimura, Yumi Kawamura, Hamid Safizadeh, Scott Simpkins, Justin Nelson, Hiroyuki Hirano, Hiroyuki Osada, Minoru Yoshida, Chad Myers, Charles Boone
Organizer
「化学コミュニケーションのフロンティア」第5回公開シンポジウム
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