Establishment of an evaluation method of a chemical-susceptibility for wildlife using counter-QSAR and machine learning

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K14988
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Kitasato University
• Principal Investigator: Takeda Kazuki 北里大学, 獣医学部, 講師 (00896350)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 動物種差 / 化学物質感受性 / 中毒 / AlphaFold2 / 分子動力学 / 分子ドッキング / 農薬 / 医薬品

Outline of Final Research Achievements

Chemicals cause a variety of damage to wildlife, sometimes resulting in local extinction of populations. For this reason, it is essential to evaluate the sensitivity of wild animals to chemical substances, but animal experiments using these substances are contraindicated. Therefore, it is necessary to establish a method to evaluate the sensitivity of wild animals using limited information such as DNA that can be obtained non-invasively. The main factors affecting susceptibility are species differences in target molecules and detoxification-metabolizing enzymes. As a non-invasive evaluation method, we conducted simulations using 3D structures of target molecules and metabolic enzymes constructed from DNA information. As an example of our achievement, we were able to evaluate the effect of a single amino acid polymorphism on rodenticide resistance, showing the possibility of using genetic information to evaluate chemical sensitivity.

Free Research Field

環境毒性学

Academic Significance and Societal Importance of the Research Achievements

野生動物での毒性試験は希少種保護の観点から困難であり、これらの化学物質感受性評価は立ち遅れている。一方、DNAは被毛から非侵襲的に入手できるため野生動物においても遺伝子解析は容易である。本研究で実施したin silicoモデリング評価系は、DNA情報を活用する事で野生動物研究の制限を超え、生体レベルでの感受性評価を可能とする独創的な研究である。本研究手法は標的分子・代謝酵素を変える事で殺鼠剤以外の化学物質へも応用可能だと予想される。当該研究は従来種差の壁が阻んでいた野生動物の化学物質感受性評価を世界に先駆け可能とする環境毒性学におけるトランスフォーマティブリサーチとなり得る。