A chemical genomics approach for understanding chemical communication

• Project Area: Frontier research of chemical communications
• Project/Area Number: 17H06411
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• Research Institution: Institute of Physical and Chemical Research
• 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)
• 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, 副チームリーダー (60360658)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥76,180,000 (Direct Cost: ¥58,600,000、Indirect Cost: ¥17,580,000); Fiscal Year 2021: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000); Fiscal Year 2020: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000); Fiscal Year 2019: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000); Fiscal Year 2018: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000); Fiscal Year 2017: ¥13,780,000 (Direct Cost: ¥10,600,000、Indirect Cost: ¥3,180,000)
• Keywords: chemical genomics / yeast / chemical communication / CRISPR / HAP1

Outline of Final Research Achievements

We established a comprehensive chemical genomics (CG) analysis pipeline, employing various diagnostic sets of mutant budding yeast, Saccharomyces cerevisiae. We assembled a set of ~5,000 non-essential genes as viable haploid deletion mutants (HAP), and we generated several strain sets that span ~1,000 essential yeast genes, including a set of heterozygous diploid deletion mutants (HET), a set of temperature-sensitive (TS) mutants and a set of gene overexpression (MoBY) strains. We also established the fission yeast Schizosaccharomyces pombe version of CG pipeline with a set of ~2,200 non-essential genes (SpHAP). CG profiles of all strain collections often provide complementary evidence for target identification. We screened these HAP/HET/TS/MoBY strains against bioactive compounds. Moreover, we launched a human cell CG screening system. Thus, advancing our platform from yeast to human CG screening will yield high-quality molecules that are relevant for the development of drug leads.

Academic Significance and Societal Importance of the Research Achievements

化合物の標的同定は創薬シーズ開発に重要であるばかりでなく、基礎研究に有用なケミカルツール分子の創成にも貢献する。我々が確立した、物理的相互作用によらず、化学遺伝学的相互作用をもとにした酵母ケミカルゲノミクス解析法は汎用性が広い。さらに本研究を発展させ、ヒト細胞のケミカルゲノミクス解析パイプラインにも着手できた。多種多様な生理活性物質の作用機序解明に有効な方法開発を達成したというインパクトは学術的にも社会的にも大きい。

Research Products

• [Int'l Joint Research] University of Toronto/The University of British Columbia(カナダ)
• [Int'l Joint Research] University of Minnesota(米国)
• [Int'l Joint Research] ETH Zurich(スイス)
• [Int'l Joint Research] University of Toronto/The University of British Columbia(カナダ)
• [Int'l Joint Research] University of Minnesota(米国)
• [Int'l Joint Research] University of Toronto(カナダ)
• [Int'l Joint Research] University of Minnesota(米国)
• [Int'l Joint Research] トロント大学/マギル大学/ブリティッシュコロンビア大学(カナダ)
• [Int'l Joint Research] ミネソタ大学/Yumanity(米国)
• [Int'l Joint Research] National Center for Drug Screening(中国)
• [Int'l Joint Research] トロント大学/マギル大学/ブリティッシュコロンビア大学(カナダ)
• [Int'l Joint Research] ミネソタ大学(米国)
• [Int'l Joint Research] the National Center for Drug Screening(中国)
• [Journal Article] Jerveratrum-Type Steroidal Alkaloids Inhibit β-1,6-Glucan Biosynthesis in Fungal Cell Walls (2022)
  • Author(s): Kubo Karen、Itto-Nakama Kaori、Ohnuki Shinsuke、Yashiroda Yoko、Li Sheena C.、Kimura Hiromi、Kawamura Yumi、Shimamoto Yasuhiro、Tominaga Ken-Ichi、Yamanaka Daisuke、Adachi Yoshiyuki、Takashima Shinichiro、Noda Yoichi、Boone Charles、Ohya Yoshikazu
  • Journal Title: Microbiology Spectrum Volume: 10 Issue: 1
  • DOI: 10.1128/spectrum.00873-21
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High-throughput platform for yeast morphological profiling predicts the targets of bioactive compounds (2022)
  • Author(s): Ohnuki, S., Ogawa, I., Itto-Nakama, K., Lu, F., Ranjan, A., Kabbage, M., Gebre, AA., Yamashita, M., Li, SC., Yashiroda, Y., Yoshida, S., Usui, T., Piotrowski, JS., Andrews, BJ., Boone, C., Brown, GW., Ralph, J., Ohya, Y.
  • Journal Title: npj Systems Biology and Applications Volume: 8 Issue: 1 Pages: 3-3
  • DOI: 10.1038/s41540-022-00212-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Leveraging machine learning essentiality predictions and chemogenomic interactions to identify antifungal targets (2021)
  • Author(s): Fu, C., Zhang, X., Veri, AO., Iyer, KR., Lash, E., Xue, A., Yan, H., Revie, NM., Wong, C., Lin, ZY., Polvi, EJ., Liston, SD., VanderSluis, B., Hou, J., Yashiroda, Y., Gingras, AC., Boone, C., O'Meara, TR., O'Meara, MJ., Noble, S., Robbins, N., Myers, CL., Cowen, LE.
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 6497-6497
  • DOI: 10.1038/s41467-021-26850-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Improving measures of chemical structural similarity using machine learning on chemical-genetic interactions (2021)
  • Author(s): Safizadeh, H., Simpkins, SW., Nelson, J., Li, SC., Piotrowski, JS., Yoshimura, M., Yashiroda, Y., Hirano, H., Osada, H., Yoshida, M., Boone, C., Myers, CL.
  • Journal Title: Journal of Chemical Information and Modeling Volume: 61 Issue: 9 Pages: 4156-4172
  • DOI: 10.1021/acs.jcim.0c00993
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clionamines stimulate autophagy, inhibit Mycobacterium tuberculosis survival in macrophages, and target Pik1 (2021)
  • Author(s): Persaud, R., Li, SC., Chao, JD., Forestieri, R., Donohue, E., Balgi, AD., Zheng, X., Chao, JT., Yashiroda, Y., Yoshimura, M., Loewen, CJR., Gingras, AC., Boone, C., Av-Gay, Y., Roberge, M., Andersen, RJ.
  • Journal Title: Cell Chemical Biology Volume: - Issue: 5 Pages: 870-882
  • DOI: 10.1016/j.chembiol.2021.07.017
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genome-wide Screening of Genes Associated with Momilactone B Sensitivity in the Fission Yeast (2021)
  • Author(s): Keisuke Tomita, Yoko Yashiroda, Yasuhiro Matsuo, Jeff S Piotrowski, Sheena C Li, Reika Okamoto, Mami Yoshimura, Hiromi Kimura, Yumi Kawamura, Makoto Kawamukai, Charles Boone, Minoru Yoshida, Hideaki Nojiri, Kazunori Okada
  • Journal Title: G3 (Bethesda) Volume: 11 Issue: 8
  • DOI: 10.1093/g3journal/jkab156
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A genome-scale yeast library with inducible expression of individual genes (2021)
  • Author(s): Arita, Y., Kim, G., Li, Z., Friesen, H., Turco, G., Wang, RY., Climie, D., Usaj, M., Hotz, M., Stoops, EH., Baryshnikova, A., Boone, C., Botstein, D., Andrews, BJ., McIsaac, RS.
  • Journal Title: Molecular Systems Biology Volume: 17 Issue: 6
  • DOI: 10.15252/msb.202110207
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Environmental robustness of the global yeast genetic interaction network (2021)
  • Author(s): Costanzo, M., Hou. J., Messier, V., Nelson, J., Rahman, M., VanderSluis, B., Wang, W., Pons, C., Ross, C., Usaj, M., San Luis, BJ., Shuteriqi, E., Koch, EN., Aloy, P., Myers, CL., Boone, C., Andrews, B.
  • Journal Title: Science Volume: 372 Issue: 6542
  • DOI: 10.1126/science.abf8424
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Genetic profiling of protein burden and nuclear export overload. (2020)
  • Author(s): Kintaka R, Makanae K, Namba S, Kato H, Kito K, Ohnuki S, Ohya Y, Andrews BJ, Boone C, Moriya H.
  • Journal Title: Elife Volume: 9
  • DOI: 10.7554/elife.54080
  • NAID: 120006941058
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Systematic genetics and single-cell imaging reveal widespread morphological pleiotropy and cell-to-cell variability (2020)
  • Author(s): Mattiazzi Usaj M, Sahin N, Friesen H, Pons C, Usaj M, Masinas MPD, Shuteriqi E, Shkurin A, Aloy P, Morris Q, Boone C, Andrews BJ.
  • Journal Title: Mol Syst Biol Volume: 16 Issue: 2
  • DOI: 10.15252/msb.20199243
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Integrating yeast chemical genomics and mammalian cell pathway analysis (2019)
  • 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.
  • Journal Title: Acta Pharmacol. Sin. Volume: 40 Issue: 9 Pages: 1245-1255
  • DOI: 10.1038/s41401-019-0231-y
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Intraspecies cell-cell communication in yeast (2019)
  • Author(s): Yashiroda, Y., Yoshida, Y.
  • Journal Title: FEMS Yeast Res. Volume: 19 Issue: 7
  • DOI: 10.1093/femsyr/foz071
  • Peer Reviewed
• [Journal Article] Using BEAN-counter to quantify genetic interactions from multiplexed barcode sequencing experiments (2019)
  • Author(s): Simpkins SW, Deshpande R, Nelson J, Li SC, Piotrowski JS, Ward HN, Yashiroda Y, Osada H, Yoshida M, Boone C, Myers CL
  • Journal Title: Nature Protocols Volume: 14 Issue: 2 Pages: 415-440
  • DOI: 10.1038/s41596-018-0099-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Predicting bioprocess targets of chemical compounds through integration of chemical-genetic and genetic interactions (2018)
  • Author(s): Simpkins SW, Nelson J, Deshpande R, Li SC, Piotrowski JS, Wilson EH, Gebre AA, Safizadeh H, Okamoto R, Yoshimura M, Costanzo M, Yashiroda Y, Ohya Y, Osada H, Yoshida M, Boone C, Myers CL
  • Journal Title: PLoS Computational Biology Volume: 14 Issue: 10 Pages: e1006532-e1006532
  • DOI: 10.1371/journal.pcbi.1006532
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] MOSAIC: a chemical-genetic interaction data repository and web resource for exploring chemical modes of action (2018)
  • Author(s): Nelson J, Simpkins SW, Safizadeh H, Li SC, Piotrowski JS, Hirano H, Yashiroda Y, Osada H, Yoshida M, Boone C, Myers CL.
  • Journal Title: Bioinformatics Volume: 34 Issue: 7 Pages: 1251-1252
  • DOI: 10.1093/bioinformatics/btx732
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Functional annotation of chemical libraries across diverse biological processes. (2017)
  • Author(s): Piotrowski JS, Li SC, Deshpande R.......Shirahige K,......Boone C.
  • Journal Title: Nat Chem Biol. Volume: 13 Issue: 9 Pages: 982-993
  • DOI: 10.1038/nchembio.2436
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 酵母の増殖阻害活性を示す含ホウ素化合物の作用機序解析 (2022)
  • Author(s): 八代田陽子、木村寛美、吉村麻美、臼井正哉、丹羽節、高橋一光、俣賀宣子、細谷孝充、Laurean Ilies、吉田稔、Charles Boone
  • Organizer: 日本農芸化学会2022年度大会
• [Presentation] 植物由来のジテルペン化合物Momilactone Bは細胞内のROSレベルを減少させることで細胞の増殖を阻害する (2022)
  • Author(s): 富田啓介、松尾安浩、八代田陽子、吉田稔、川向誠、野尻秀昭、岡田憲典
  • Organizer: 日本農芸化学会2022年度大会
• [Presentation] 奇数鎖脂肪酸による分裂酵母の脂質組成の攪乱および小胞体の形態異常 (2022)
  • Author(s): 星川陽次郎、西村慎一、松山晃久、Sheena Li、八代田陽子、Charles Boone、津川裕司、有田誠、吉田稔
  • Organizer: 日本農芸化学会2022年度大会
• [Presentation] 奇数鎖脂肪酸による分裂酵母の脂質代謝攪乱と細胞分裂阻害 (2021)
  • Author(s): 星川陽次郎、西村慎一、松山晃久、Sheena Li、八代田陽子、Charles Boone、津川裕司、有田誠、吉田稔
  • Organizer: 第63回日本脂質生化学会
• [Presentation] 奇数鎖脂肪酸は分裂酵母において細胞膜極性と細胞分裂に異常を引き起こす (2021)
  • Author(s): 星川陽次郎、西村慎一、松山晃久、Li Sheena、八代田陽子、Boone Charles、吉田稔
  • Organizer: 日本農芸化学会2021年度大会
• [Presentation] Genetic Network Analysis of the NGLY1 Pathway (2020)
  • Author(s): Charles Boone
  • Organizer: International Symposium on Glyco-lipidologue
  • Int'l Joint Research / Invited
• [Presentation] 酵母ケミカルゲノミクス法による化合物の標的同定 (2019)
  • Author(s): 八代田陽子
  • Organizer: 第19回日本蛋白質科学会年会第71回日本細胞生物学会大会合同年次大会共催シンポジウム「化学コミュニケーションのフロンティア」
  • Invited
• [Presentation] An Integrated Chemical Genomic Approach for Target Identification (2019)
  • 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
• [Presentation] Target identification using a yeast chemical genomic approach (2019)
  • Author(s): Yoko Yashiroda, Sheena Li, Hiroyuki Osada, Minoru Yoshida, Chad Myers, Charles Boone
  • Organizer: 酵母遺伝学フォーラム第52回研究報告会
• [Presentation] 酵母ケミカルゲノミクス法を用いた化合物の標的同定 (2019)
  • Author(s): 八代田陽子、吉村麻美、野口峻太朗、Sheena Li、木村寛美、河村優美、吉田稔、酒井隆一、Charles Boone
  • Organizer: 「化学コミュニケーションのフロンティア」第6回公開シンポジウム
• [Presentation] Yeast chemical genomics approach for target identification (2019)
  • Author(s): 八代田 陽子
  • Organizer: The 5th CSRS-ITbM Joint Workshop
• [Presentation] Yeast Chemical Genomic Approach for Target Identification (2019)
  • Author(s): Yoko Yashiroda
  • Organizer: ACBI 2019 Yangon Meeting
  • Int'l Joint Research / Invited
• [Presentation] Target identification using an integrated chemical genomic approach (2019)
  • Author(s): Sheena Li, Mami Yoshimura, Hamid Safizadhe, Scott Simpkins, Justin Nelson, Yuichi Shichino, Yoko Yashiroda, Shintaro Iwasaki, Hiroyuki Hirano, Hiroyuki Osada, Minoru Yoshida, Chad Myers, Charles Boone
  • Organizer: The 1st International Symposium on Chemical Communication (ISCC2019)
  • Int'l Joint Research
• [Presentation] Identification of an inhibitor of the yeast fatty acid synthase (2019)
  • Author(s): Yoko Yashiroda, Sheena Claire Li, Mami Yoshimura, Hiromi Kimurs, Norio Kudo, Hamid Safizadhe, Scott Simpkins, Justin Nelson, Hiroyuki Hirano, Hiroyuki Osada, Minoru Yoshida, Chad Myers, Charles Boone
  • Organizer: The 1st International Symposium on Chemical Communication (ISCC2019)
  • Int'l Joint Research
• [Presentation] Target identification using an integrated chemical genetic approach (2018)
  • Author(s): Sheena Li
  • Organizer: Yeast Genetics Meeting
  • Int'l Joint Research
• [Presentation] Target integration using an integrated chemcial genetic approach (2018)
  • Author(s): Li Sheena, Boone Charles
  • Organizer: 新学術領域研究（研究領域提案型）「化学コミュニケーションのフロンティア」第3回公開シンポジウム
• [Presentation] Mapping Chemical-Genetic Interactions to Link Bioactive Compounds to Cellular Targets (2018)
  • Author(s): Charles Boone
  • Organizer: 新学術領域研究「化学コミュニケーションのフロンティア」第２回公開シンポジウム
  • Invited
• [Presentation] Mapping Genetic Networks on a Global Scale (2017)
  • Author(s): Charles Boone
  • Organizer: From Genetic Networks to a Cellular Wiring Diagram
  • Int'l Joint Research / Invited
• [Presentation] Target Identification Using an Integrated Chemical Genetic Approach (2017)
  • Author(s): Sheena Li, Charles Boone
  • Organizer: the CIFAR meeting
  • Int'l Joint Research
• [Presentation] 窒素代謝を変えるコミュニケーション- 脂肪酸をつかった分裂酵母の種の生存戦略 - (2017)
  • Author(s): 八代田陽子
  • Organizer: 第69回日本生物工学会 シンポジウム「微生物の「声」が聴きたくて… 単細胞生物のコミュニケーションスキル」
  • Invited
• [Presentation] 脂肪酸化合物を介した酵母細胞間のコミュニケーション (2017)
  • Author(s): 八代田陽子
  • Organizer: 第54回植物化学シンポジウム「ファイトバイオーム：植物化学物質による生物間コミュニケーションへの誘い」
  • Invited
• [Presentation] アミノ酸取り込みを調節する酵母細胞間相互作用 (2017)
  • Author(s): 八代田陽子
  • Organizer: 2017年度生命科学系学会合同年次大会 ワークショップ「ライフイベントを紡ぐ栄養環境への適応機構」
  • Invited
• [Book] 第10章 酵母ケミカルゲノミクスを用いた化合物作用機序解明のための大規模高速解析法（「酵母菌・麹菌・乳酸菌の産業応用展開」） (2018)
  • Author(s): 八代田陽子、吉田稔
  • Total Pages: 264
  • Publisher: シーエムシー出版
  • ISBN: 9784781313177
• [Remarks] Drugs Made in Nature
  • URL: https://www.thedonnellycentre.utoronto.ca/node/1341
• [Remarks] 化合物の標的機能を決定するツールを開発－酵母の化学遺伝学アプローチで化合物の標的予測／同定が迅速に－
  • URL: http://www.riken.jp/pr/press/2017/20170725_1/