基本信息

禾立春  男  研究员  博导  中国科学院精密测量科学与技术创新研究院

电子邮件: helichun@wipm.ac.cn; helichun@apm.ac.cn
通信地址: 中国科学院精密测量科学与技术创新研究院

导师简介:

中国科学院精密测量科学与技术创新研究院研究员、教授,博导。中科院BR计划入选者,湖北省BR计划入选者。主持国家重点研发计划战略性国际科技创新合作重点专项课题、国家自然科学基金委项目及瑞士自然科学基金委项目,参与国家自然科学基金委重大项目及国家重点研发计划变革性技术关键科学问题项目。在PNAS、Science Advances、Angew Chem.、JACI、The EMBO Journal等期刊发表多篇论文。

研究领域

主要研究方向:


1 核磁共振波谱技术研究蛋白质(如分子伴侣等)激发态、蛋白质动力学性质及其介导的动态相互作用

Chaperones are crucial for cellular life to ensure all proteins obtain their right fold and functionality. The promiscuous property of chaperones enables them to bind with a wide spectrum of client proteins from nascent proteins to quasi-native and native proteins. While mechanisms of chaperones aided protein folding have been intensively characterized, it is still largely unknown how chaperones act on folded clients and modulate the activity of the folded protein. To address this fundamental question, We apply NMR spectroscopy and other biophysics approaches to understand chaperone and client proteins recognition and interaction by investigating their intermediate conformations (excited state), protein dynamics modulations and the subsequently changes of its activities. 

2. 利用细菌外分泌囊泡为建立细菌感染与机体免疫反应的NMR研究体系

Bacterial outer membrane vesicles (OMVs) are nano‐sized compartments consisting of a lipid bilayer that encapsulates periplasm‐derived, luminal content. OMVs, which pinch off of Gram‐negative bacteria, are now recognized as a generalized secretion pathway which provides a means to transfer cargo to other bacterial cells as well as eukaryotic cells. Although it is well recognized that OMVs can enter and release cargo inside host cells during infection, the mechanisms of host association and uptake are not well understood. We apply biophysical, biochemical and cellular biological approaches to investigate characters of virulence factors in OMVs and study the mechanism of host cell association, uptake and innate immunue response to OMVs.


3. 核磁共振波谱技术研究CAR-T、天然免疫反应等相关跨膜蛋白及病毒垮膜蛋白信号转导机制

We applied NMR to investigate the structural and functional roles of the transmembrane and membrane-proximal regions of cell surface proteins with special focus on CAR-T transmembrane domain, innate immune response receptors and viral proteins.

4. 纳米抗体筛选及利用NMR对抗原结合表位的表征

Single-domain antibody, also known as a nanobody, is an antibody fragment from Camelid consisting of a single monomeric variable antibody domain. It has a molecular weight of only 12–15 kDa. Nevertheless it is able to bind with a particular antigen with a high affinity. Besides higher affinity, smaller size, nanobody also has other advantages such as higher stability and easy expression in E.coli facilitating isotope labeling and epitope mapping via NMR.


招生信息

招收博士研究生、硕士研究生


专业方向:分析化学 (07开头)、生物化学、生物工程、生物技术(08开头)等


学术兼职

   
社会兼职

Reviewer: 

2021-06 至 - Nucleic Acids Research 杂志审稿人 

2019-01 至 - Nature Communication 杂志审稿人 

Editor & Membership 

2021年 当选湖北省晶体学会理事 

2021年 担任 Life 杂志Special Issue Editor 

2021年 担任 Biomolecules 杂志 Topical Advisory Panel Editor

2019年 入选科技部会同有关部门建立的国家科技专家库

出版信息

(1) Cellular stress promotes NOD1/2-dependent inflammation via the endogenous metabolite sphingosine-1-phosphate, The EMBO Journal, 2021 in press

(2) NMR-Based Methods for Protein Analysis, Anal Chem., 2020

(3) Mechanisms of Chaperones as Active Assistant/Protector for Proteins: Insights from NMR Studies, Chinese Journal of Chemistry, 2019-12

(4) Frustrated Interfaces Facilitate Dynamic Interactions between Native Client Proteins and Holdase Chaperones, ChembioChem, 2019-06

(5) Common Patterns in Chaperone Interactions with a Native Client Protein., Angew.Chemie Int. Ed., 2018,

(6) An unexpected protective role of low affinity allergen-specific IgG via the inhibitory receptor FcrRIIb, J. Allergy Clin. Immunol., 2017, 

(7) Therapeutic silence of pleiotrophin by targeted delivery of siRNA and its effect on the inhibition of tumor growth and metastasis, PLoS One, 2017

(8) A molecular mechanism of chaperone-client recognition., Science Advances, 2016

(9) Structure determination of helical filaments by solid-state NMR spectroscopy, Proc Natl Acad Sci U S A., 2016

(10) Solid-state NMR resonance assignments of the filament-forming CARD domain of the innate immunity signaling protein MAVS, Biomol NMR Assign., 2014

(11) Expression, purification, refolding, and characterization of octreotide-interleukin-2: a chimeric tumor-targeting protein, Int J Mol Med., 2011


科研活动

科研项目


( 1 ) 中国科学院BR计划择优支持, 主持, 国家级

( 2 ) 分子伴侣Hsp70对折叠客户 蛋白动力学性质及功能的影响, 主持, 自然科学基金委青年项目

​( 3 ) 分子伴侣去折叠客户蛋白机制研究, 主持, 自然科学基金委面上项目

( 4 ) 细胞外激发态蛋白NMR 标记与检测方法, 主持,课题负责人, 国家重点研发计划

( 5 )The molecular basis for the regulation of substrate activity by a eukaryotic chaperone, 主持,瑞士自然科学基金项目

( 6 ) 细胞中生物大分子结构与相互作用 的谱学测量, 参与, 国家级

( 7 ) 肺癌的超高灵敏谱学与成像新技术研究, 参与, 国家级


学术会议


(1)Investigation of the modulation of native client protein dynamics and activites by chaperone Hsp70  新加坡  2019-07-03
(2)Investigation of the dynamic interaction between client proteins and chaperones via NMR  北京  2019-05-29
(3)Investigation of dynamics and interactions between client proteins and chaperones via NMR   北京  2019-05-18
(4)Mechanisms of client recognition, interaction and release by the chaperone Spy   美国 2016-07-24
(5)Structure and dynamics of chaperone spy intereaction with its substrate im7  瑞士  2015-09-23
(6)Structure and dynamics of the periplasmic chaperone spy with its substrate im7  上海  2015-08-16

合作情况

瑞士 University of Basel

德国 Friedrich-Loeffler-Institut

华东理工大学, 华中科技大学, 武汉大学, 同济医学院等

指导学生

   
博士后及研究生

                     

   Gangjin Yu          Guan Wang         Yihao Chen          Saba Bashir         Yicong Liu         Zhiqing Tao       Mingjun Zhu

       Postdoc.             Graudate Student      Graudate Student       Graudate Student     Graudate Student    Graudate Student    Graudate Student



  

ChaoZhe Wang       Huan Wang

 Graudate Student       Graudate Student 


实验员

        

      Yaling Zhao                  Yang Qiao 

      Technician                   Technician 


本科毕设及实习生

Zhuoyue Jinyang

  Undergraduate


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目前实验室仍有空缺,欢迎有科研热情的本科生(毕设)、博士后(特别研究助理)加入, 邮件: helichun@apm.ac.cn