
搜索网站、位置和人员

新闻与活动 活动信息
生命科学专题学术讲座 | 孟飞龙:Multiscale regulations of AID-initiated antibody gene diversification
时间
2023年9月19日(周二)
10:30-12:00
地点
云谷校区E9-109
主持
西湖大学生命科学学院 教授 俞晓春
受众
全体师生
分类
学术与研究
生命科学专题学术讲座 | 孟飞龙:Multiscale regulations of AID-initiated antibody gene diversification
时间:9月19日星期二10:30-12:00
Time:10:30 AM-12:00 PM,Tuesday, September 19,2023
主持人:西湖大学生命科学学院教授 俞晓春
Host:Dr. Xiaochun Yu, Professor, School of Life Sciences
地点:云谷校区E9-109
Venue:E9-109, Yungu Campus
主讲嘉宾/Speaker:
Dr. Feilong Meng, PI, State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and CellBiology, Center for Excellence in Molecular Cell Science, Chinese Academy ofSciences; University of Chinese Academy of Sciences.
My research has focused on the mechanisms of antibody diversification in B lymphocytes, including antibody class switch and affinity maturation. Upon antigen stimulation, B cells can undergo cytidine deaminase AID-initiated antibody class switch recombination and somatic hypermutation processes to diversify the antigen receptor along with B cell clonal expansion. We aim to understand the molecular mechanisms underlying specific-targeting of cytidine deaminase AID, error-prone decoding of DNA lesions, and affinity-based selection of B cells. We also seek to establish new methods for antibody generation and discovery. In this course, we have uncovered genomic and epigenomic features of AID targeting at micrometer and nanometer scales, identified a critical regulator of orientation-specific DNA recombination, and invented a set of methods for ex vivo antibody affinity maturation and selection.
讲座摘要/Abstract:
Somatic hypermutation, initiated by activated-induced deaminase (AID), generates a diverse pool of mutations to allow antibody affinity maturation upon pathogen invasion. Why hypermutation is focused on the three nonconsecutive complementarity-determining-regions remains enigmatic. Here, we found that preferential mutagenesis is dependent on the mesoscale DNA sequence surrounding the AID-targeted cytidines. The in vivo hypermutation profile is mimicable in in vitro deaminase assays under physiological conditions. Mesoscale single-strand DNA sequence influences its binding to the charged-patch of AID, resulting in differential deaminase activity. We identified the short AID-attracting sequence and demonstrate their function in increasing mutability of an otherwise cold region. Our results show an unexpected non-coding role of antibody coding sequence in directing hypermutation and paved the way to the synthetic-design of antibody-humanized animal models.
联系人/Contact:
生命科学学院
于文越 yuwenyue@westlake.edu.cn