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RIKEN Center for Sustainable Resource Science Molecular Ligand Target Research Team

Team Leader: Charles Boone (Ph.D.)

Research Summary

Charles  Boone(Ph.D.)

Small molecular ligands with unique activities must have the specific target molecules that exist in their cells or organisms. Identification of the target molecules is critical for elucidating the mode of action of the molecular ligands and for drug development. However, drug target identification has been difficult in general, because the mode of interactions between the molecular ligands and their targets is not uniform. Our team aims at developing innovative techniques based on global analysis of yeast genetic interactions, which leads to quick and accurate detection of the ligand-target interactions.

Main Research Fields

  • Biology

Related Research Fields

  • Medicine, Dentistry & Pharmacy

Keywords

  • Chemical Genomics
  • Target Identification
  • Yeast

Selected Publications

  • 1.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.:
    "High-throughput platform for yeast morphological profiling predicts the targets of bioactive compounds."
    NPJ Syst. Biol. Appl., 8, 3 (2022).
  • 2.Kubo, K., Itto-Nakama, K., Ohnuki, S., Yashiroda, Y., Li, SC., Kimura, H., Kawamura, Y., Shimamoto, Y., Tominaga, KI., Yamanaka, D., Adachi, Y., Takashima, S., Noda, Y., Boone, C., Ohya, Y.:
    "Jerveratrum-type steroidal alkaloids inhibit β-1,6-glucan biosynthesis in fungal cell walls."
    Microbiol. Spectr., 10, e0087321 (2022).
  • 3.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.:
    "Leveraging machine learning essentiality predictions and chemogenomic interactions to identify antifungal targets."
    Nat. Commun. 12, 6497 (2021).
  • 4.Safizadeh, H., Simpkins, SW., Nelson, J., Li, SC., Piotrowski, JS., Yoshimura, M., Yashiroda, Y., Hirano, H., Osada, H., Yoshida, M., Boone, C., Myers, CL.:
    "Improving measures of chemical structural similarity using machine learning on chemical-genetic interaction."
    J. Chem. Inf. Model., 61, 4156-4172 (2021).
  • 5.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.:
    "Clionamines stimulate autophagy, inhibit Mycobacterium tuberculosis survival in macrophages, and target Pik1."
    Cell Chem. Biol., doi: 10.1016/j.chembiol.2021.07.017. (2021).
  • 6.Tomita, K., Yashiroda, Y., Matsuo, Y., Piotrowski, JS., Li, SC., Okamoto, R., Yoshimura, M., Kimura, H., Kawamura, Y., Kawamukai, M., Boone, C., Yoshida, M., Nojiri, H., Okada, K.:
    "Genome-wide screening of genes associated with momilactone B sensitivity in the fission yeast Schizosaccharomyces pombe."
    G3 (Bethesda), 11, jkab156 (2021).
  • 7.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.:
    "A genome-scale yeast library with inducible expression of individual genes."
    Mol. Syst. Biol., 17, e10207 (2021).
  • 8.Costanzo, M., Hou. J., Messier, V., Nelson, J., Rahman, M., VanderSluis, B., Wang, W., Pons, C., Ross, C., Ušaj, M., San Luis, BJ., Shuteriqi, E., Koch, EN., Aloy, P., Myers, CL., Boone, C., Andrews, B.:
    "Environmental robustness of the global yeast genetic interaction network."
    Science, 372, abf8424 (2021).
  • 9.Simpkins, SW., Deshpande, R., Nelson, J., Li, SC., Piotrowski, JS., Ward, HN., Yashiroda, Y., Osada, H., Yoshida, M., Boone, C., Myers, CL.:
    "Using BEAN-counter to quantify genetic interactions from multiplexed barcode sequencing experiments."
    Nat. Protoc., 14, 415-440 (2019).
  • 10.Piotrowski, JS., Li, SC., Deshpande, R., Simpkins, SW., Nelson, J., Yashiroda, Y., Barber, JM., Safizadeh, H., Wilson, E., Okada, H., Gebre, AA., Kubo, K., Torres, NP., LeBlanc, MA., Andrusiak, K., Okamoto, R., Yoshimura, M., van Leeuwen, J., Shirahige, K., Baryshnikova, A., Brown, GW., Hirano, H., Costanzo, M., Andrews, B., Ohya, Y., Osada, H., Yoshida, M., Myers, CL., and Boone, C.:
    "Functional annotation of chemical libraries across diverse biological processes."
    Nat. Chem. Biol., 13, 982–993 (2017).

Recent Research Results

Related Links

Lab Members

Principal investigator

Charles Boone
Team Leader

Core members

Yoko Yashiroda
Deputy Team Leader
Lien Thi Kim Pham
Postdoctoral Researcher
Mami Yoshimura
Technical Staff I

Contact Information

N202 Sustainable Resource Science Building,
2-1 Hirosawa,
Wako, Saitama
351-0198, Japan

Email: charlieboone [at] riken.jp

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