RIKEN Center for Sustainable Resource Science Molecular Ligand Target Research Team

Team Leader: Charles Boone (Ph.D.)

Japanese Page

Research Summary

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.Iyer, KR., Li, SC., Revie, NM., Lou, JW., Duncan, D., Fallah, S., Sanchez, H., Skulska, I., U?aj, MM., Safizadeh, H., Larsen, B., Wong, C., Aman, A., Kiyota, T., Yoshimura, M., Kimura, H., Hirano, H., Yoshida, M., Osada, H., Gingras, AC., Andes, DR., Shapiro, RS., Robbins, N., Mazhab-Jafari, MT., Whitesell, L., Yashiroda, Y., Boone, C., Cowen, LE.:
"Identification of triazenyl indoles as inhibitors of fungal fatty acid biosynthesis with broad-spectrum activity"
Cell Chem. Biol., 30, 795-810 (2023).
2.Saeki, N., Yamamoto, C., Eguchi, Y., Sekito, T., Shigenobu, S., Yoshimura, M., Yashiroda, Y., Boone, C., Moriya, H.:
"Overexpression profiling reveals cellular requirements in the context of genetic backgrounds and environments"
PLoS Genetics 19 (4), e1010732 (2023).
3.Forster, DT., Li, SC., Yashiroda, Y., Yoshimura, M., Li, Z., Isuhuaylas, LAV., Itto-Nakama, K., Yamanaka, D., Ohya, Y., Osada, H., Wang, B., Bader, GD., Boone, C.:
"BIONIC: biological network integration using convolutions"
Nat Methods 19, 1250-1261 (2022).
4.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).
5.Revie, NM., Iyer, KR., Maxson, ME., Zhang, J., Yan, S., Fernandes, CM., Meyer, KJ., Chen, X., Skulska, I., Fogal, M., Sanchez, H., Hossain, S., Li, S., Yashiroda, Y., Hirano, H., Yoshida, M., Osada, H, Boone, C., Shapiro, RS., Andes, DR., Wright, GD., Nodwell, JR., Del Poeta, M., Burke, MD., Whitesell, L., Robbins, N., Cowen, LE.:
"Targeting fungal membrane homeostasis with imidazopyrazoindoles impairs azole resistance and biofilm formation"
Nat Commun 13: 3634 (2022).
6.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).
7.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).
8.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).
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).