計画研究
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.
2: おおむね順調に進展している
We accomplished the mission as planned. We are currently preparing a manuscript for our chemical genomic pipeline.
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.
（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）
すべて 2020 2019 その他
すべて 国際共同研究 (2件) 雑誌論文 (2件) (うち国際共著 1件、 査読あり 2件) 学会発表 (5件) (うち国際学会 1件、 招待講演 2件) 備考 (1件)
Acta Pharmacol. Sin.
巻: 40 ページ: 1245, 1255
10.1038/s41401-019-0231-y
FEMS Yeast Res.
巻: 19 ページ: foz071
10.1093/femsyr/foz071
https://www.thedonnellycentre.utoronto.ca/node/1341
