【廿周年院庆学术报告117 】 · 【物理格致论坛第120期】
一、报告题目：Kinetic Determinants of CRISPR/Cas9 Gene Editing: Insights from Data Learning and Energy Landscape Analysis
二、报告人：Prof. Shi-Jie Chen (陈世杰教授)
三、时 间：2023年12月21日（周四）10:00-11:00
四、地 点：闻理园A4-218
报告摘要：Evaluation of CRISPR Cas9 cleavage efficiency and design of strategies to mitigate off-target effect require a mechanistic understanding and accurate modeling for CRISPR genome editing. The conventional perspective on CRISPR genome editing assumes a state of thermal equilibrium, governed by the principles of equilibrium thermodynamics. However, experimental investigations have suggested that the system is not in equilibrium, and, as a result, the process adheres to the principles of nonequilibrium kinetics. To address this, we leverage large-scale genome editing data and combine supervised machine learning with free energy landscape analysis and kinetic simulations. This integrated approach has yielded significant insights: it revealed a direct correlation between CRISPR cleavage efficiency and the rate of R-loop unfolding, identifying it as the key determinant for CRISPR cleavage efficiency. The finding led to the development of a predictive model for CRISPR based on nonequilibrium kinetics. This novel model not only unveils previously unidentified, yet biologically significant intermediates and pathways but also results in a highly accurate predictive model for both on-target and off-target genome editing. Consequently, it provides a new design strategy for maximizing and minimizing on-target and off-target cleavages, respectively.
报告人简介：陈世杰教授是美国密苏里大学董事会冠名杰出教授。陈教授任职于密苏里大学物理与天文系、生物化学系、数据科学与信息学研究院。 他1987年毕业于浙大物理学专业，获学士学位。后通过李政道先生倡导组织的CUSPEA项目到美国学习；1994年获得University of California-San Diego的物理学博士学位，方向为理论等离子体物理。2012年当选为美国物理学会（APS）Fellow。 2018年当选为美国科学促进会（AAAS) Fellow。陈世杰教授是《PLoS-Computational Biology》Associate Editor；国际RNA纳米技术与纳米医学学会创始理事会成员，美国国家卫生研究院NIH和美国国家基金委NSF多个重要项目的主持人，先后在Nature Communications, PNAS, JACS, Annual Review of Biophysics, Nucleic Acids Research等杂志上发表百余篇论文。
研究组网站http://vfold.missouri.edu/
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