禾立春 男 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
通信地址： 中国科学院精密测量科学与技术创新研究院
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. 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.
4. 核磁共振波谱技术指导酶等蛋白质的定向进化
Directed evolution offers a valuable method to enhance existing characteristics and introduce entirely new functionalities to protein. However, the potential of this approach is naturally limited to small proteins due to the vast number of possible amino acid sequences. To explore the complete sequence space of a protein larger than 100 amino acids, one would need to test an overwhelming 20e100 combinations, surpassing the capabilities of current experimental methods. Nevertheless, functional hot spots in enzymes can be identified using NMR spectroscopy, offering simplicity in improving the activity of enzymes. As it does not require any prior knowledge of the protein's structure or bioinformatics. We anticipate its wide applicability and its ability to unlock the full potential of directed enzyme evolution.
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
2023年 担任科技部国家科技基础条件平台中心 生物试剂专委会 副主任委员
2023年 担任湖北省生物化学与分子生物学会理事
2021年 担任Cell 旗下刊物 The Innovation杂志青年编委
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
发表论文：
(1). Expression, purification, refolding, and characterization of octreotide-interleukin-2: a chimeric tumor-targeting protein, Int J Mol Med., 2011
(2). Solid-state NMR resonance assignments of the filament-forming CARD domain of the innate immunity signaling protein MAVS, Biomol NMR Assign., 2014
(3). Structure determination of helical filaments by solid-state NMR spectroscopy, Proc Natl Acad Sci U S A., 2016
(4). A molecular mechanism of chaperone-client recognition., Science Advances, 2016
(5). Therapeutic silence of pleiotrophin by targeted delivery of siRNA and its effect on the inhibition of tumor growth and metastasis, PLoS One, 2017
(6). An unexpected protective role of low affinity allergen-specific IgG via the inhibitory receptor FcrRIIb, J. Allergy Clin. Immunol., 2017
(7). Common Patterns in Chaperone Interactions with a Native Client Protein., Angew.Chemie Int. Ed., 2018
(8). Frustrated Interfaces Facilitate Dynamic Interactions between Native Client Proteins and Holdase Chaperones, ChembioChem, 2019
From 2019
(1). Mechanisms of Chaperones as Active Assistant/Protector for Proteins: Insights from NMR Studies, Chinese Journal of Chemistry, 2019-12
(2). NMR-Based Methods for Protein Analysis, Anal Chem., 2020
(3). Cellular stress promotes NOD1/2-dependent inflammation via the endogenous metabolite sphingosine-1-phosphate, The EMBO Journal, 2021
(4). Chaperone Spy Protects Outer Membrane Proteins from Folding Stress via Dynamic Complex Formation, mBio, 2021
(5). Backbone resonance assignments and dynamics of S. cerevisiae SERF, Biomolecular NMR Assignments, 2022
(6). Molecular Insight into the Extracellular Chaperone Serum Albumin in Modifying the Folding Free Energy Landscape of Client Proteins, Journal of Physical Chemistry Letters, 2022
(7). Self-Assembled Oligopeptide (FK)4 as a Chiral Alignment Medium for the Anisotropic NMR Analysis of Organic Compounds，ACS Applied Materials & Interfaces, 2022
(8). Diverse Roles of ScSERF in Modifying the Fibril Growth of Amyloidogenic Proteins. Chemistry, 26;29(30): e202203965, 2023
(9). Protein Conformational Exchanges Modulated by the Environment of Outer Membrane Vesicles,J Phys Chem Lett. 14 (11):2772-2777, 2023
(10). Enrichment and delivery of target proteins into the cell cytosol via Outer Membrane Vesicles. ACS Applied Materials & Interfaces. 2023
(11). Protein methylation characterization using NMR without isotopic labeling. Talanta, 2023
(12). A method for rapid nanobody screening with no bias of the library diversity, iScience, 2024
(13). A tale of dual functions of SERF family proteins in regulating amyloid formation. ChemBioChem， 2024
(14). NMR spectroscopy for metabolomics in the living system: recent progress and future challenges. Analytical and Bioanalytical Chemistry， 2024
(15). Temperature-controllable Liquid Crystalline Medium for Stereochemical Elucidation of Organic Compounds via Residual Chemical Shift Anisotropies. Analytical Chemistry， 2024
出版专著：
（1） Biophysics of Molecular Chaperones: Function, Mechanisms and Client Protein Interactions, Royal Society of Chemistry, 2023
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 ) 酶激发态结构解析， 中国科学院先导专项，主持，课题负责人
( 7 ) 细胞中生物大分子结构与相互作用 的谱学测量, 基金委重大项目，参与, 国家级
( 8 ) 肺癌的超高灵敏谱学与成像新技术研究, 科技部重点研发计划， 参与, 国家级
( 9 ) 湖北省创新群体项目，参与
学术会议
（1）分子伴侣功能与机制研究，北京，2021-09-29
（2）Investigation of the modulation of native client protein dynamics and activites by chaperone Hsp70 新加坡 2019-07-03
（3）Investigation of the dynamic interaction between client proteins and chaperones via NMR 北京 2019-05-29
（4）Investigation of dynamics and interactions between client proteins and chaperones via NMR 北京 2019-05-18
（5）Mechanisms of client recognition, interaction and release by the chaperone Spy 美国 2016-07-24
（6）Structure and dynamics of chaperone spy intereaction with its substrate im7 瑞士 2015-09-23
（7）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
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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