刘冰

结构生物学（核磁共振波谱学）；

微生物耐药性机制；

病原体入侵宿主机制。

1、个人专长：

2000年考入中国科技大学，同年公派留学至新加坡国立大学，2005年获得新加坡国立大学化学与生命科学双学士学位，同年10月进入英国皇家科学院院士Prof. Iain Campbell团队，师从帝国理工学院核磁共振中心主任、结构生物学主席Prof. Steve Matthews。2010年获得帝国理工学院博士学位后，长期就职于英国帝国理工学院，相继担任研究助理、助理研究员、高级助理研究员（博士生导师）等职务。2018年2月受聘于西安交通大学青年拔尖人才，教授。研究工作主要集中在对病原微生物，尤其是病毒、细菌、原生生物等入侵过程中起重要作用的蛋白质进行结构解析和功能的研究，为阐明微生物入侵及耐药机制，阻断和抑制微生物侵犯机体作出了重要贡献。申请者前期使用多种生物化学手段，以核磁共振波谱法（NMR）为主，对多个具有重要功能的关键蛋白质及蛋白质聚合物进行了结构鉴定与功能分析。作为第一完成人解析蛋白结构12个，合作完成解析5个蛋白，并指导超过20个蛋白结构的解析。目前已在国际核心期刊发表科研论文发表文章20篇，其中11篇以第一作者(含并列）发表于Nucleic Acids Research，PNAS等杂志。

针对细菌多重耐药性的严重问题，申请者拟从细菌内部面对外界生存压力（包括抗生素）对Sigma S的调控获得的生存机制，以及从外部研究噬菌体SPO1抑制革兰氏阳性菌生长的原理开展双向研究，旨在揭示抗生素耐药的机制和提供全新的治疗策略。

1.Sigma S 因子相关调控蛋白的结构解析与功能研究

从结构生物学的角度，通过NMR技术解析细菌σ^S的调控因子RssB以及反调控因子Ira家族中关键蛋白的结构，明确细菌对σ^S的调控机制以及关键蛋白的功能与相互作用，为阐明细菌σ^S的调控机制提供原子水平上的证据，推动细菌耐药机理的深入研究，调节通路中的关键蛋白将成为抗生素研究的新靶点。

2.枯草杆菌噬菌体SPO1宿主接管模块的结构与功能研究

从分子生物和结构生物学角度，系统研究革兰氏阳性菌模式生物枯草杆菌的专属噬菌体——SPO1的入侵机制，通过对SPO1宿主接管模块中全新的蛋白结构进行解析，并详细阐述SPO1 对G+菌发挥抑菌作用的关键蛋白的功能与作用机理。前期已筛选出8个全新的抑菌性蛋白，并发现多个噬菌体蛋白的全新功能，首次解析出模块中Gp44的三维结构，构建并部分验证了全新的抑菌模型。这些成果在噬菌体研究中均属首次，并将继续对包括Gp44在内的多个关键蛋白开展系统的结构与功能研究，为G+菌噬菌体治疗策略提供有价值的结构生物学基础。

同时在冷冻电镜方面，对生命代谢中核心的蛋白质聚合体包括ClpC， ClpXP等进行结构鉴定。

Darvill N, Dubois D, Rouse S, Hammoudi P, Blake T, Benjamin S, Liu B, Dominique S, Matthews S, 2018, Structural Basis of Phosphatidic Acid Sensing by APH in Apicomplexan Parasites, Structure, doi.org/10.1016/j.str.2018.05.001 IF: 4.9

Tabib-Salazar A#, Liu B#, Barker D, Burchell L, Qimron U, Matthews S*, Wigneshweraraj S*, 2018, A T7 phage factor required for managing RpoS in Escherichia coli, PNAS，doi.org/10.1073/pnas.1800429115 IF: 9.5

Liu B, Wang Z, Lan L, Yang Q, Zhang P, Shi L, Lang Y, Tabib-Salazar A, Wigneshweraraj S, Zhang J, Wang Y, Tang Y, Matthews S*, Zhang X*, 2018, A Rapid Colorimetric Method to Visualize Protein Interactions. Chemistry: A European Journal, DOI:10.1002/chem.201800401 IF: 5.1

Tabib-Salazar A#, Liu B#, Shadrin A, Mekler V, Xu Y, Severinov K, Matthews S*, Wigneshweraraj S*, 2017，Full shut-off of Escherichia coli RNA-polymerase by T7 phage requires a small phage-encoded DNA-binding protein, NUCLEIC ACIDS RESEARCH, 2017. Doi: 10.1093/nar/gkx370 IF: 11.6

Zhang P, Yang X, He Y, Chen Z, Liu B, Cota E, Yang G, Wang W, Zhang J, Lin R, 2017, Preparation, characterization and toxicity evaluation of amphotericin B loaded MPEG-PCL micelles and its application for buccal tablets , APPLIED MICROBIOLOGY AND BIOTECHNOLOGY. DOI:10.1007/s00253-017-8463-6 IF: 3.4

Jønsson R#, Liu B#, Struve C, Yang Y, Jørgensen R, Xu Y, Jenssen H, Krogfelt KA, Matthews S, 2016, Structural and functional studies of Escherichia coli aggregative adherence fimbriae (AAF/V) reveal a deficiency in extracellular matrix binding., Biochim Biophys Acta IF: 2.8

Liang X#, Liu B#, Zhu F#, Scannapieco FA, Haase EM, Matthews S, Wu H, 2016, A distinct sortase SrtB anchors and processes a streptococcal adhesin AbpA with a novel structural property, Scientific Reports, Vol: 6, ISSN: 2045-2322 IF: 4.6

Huynh M-H#, Liu B#, Henry M, Liew L, Matthews SJ, Carruthers VB, 2015, Structural Basis of Toxoplasma gondii MIC2-associated Protein Interaction with MIC2, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 290, Pages: 1432-1441, ISSN: 0021-9258 IF: 4.6

Liu B, Zhu F, Wu H, Matthews S, 2015, NMR assignment of the amylase-binding protein A from Streptococcus parasanguinis, BIOMOLECULAR NMR ASSIGNMENTS, Vol: 9, Pages: 173-175, ISSN: 1874-2718 IF: 0.8

Liu B#, Shadrin A#, Sheppard C, Mekler V, Xu Y, Severinov K, Matthews S, Wigneshweraraj S, 2014, A bacteriophage transcription regulator inhibits bacterial transcription initiation by Sigma-factor displacement, NUCLEIC ACIDS RESEARCH, Vol: 42, Pages: 4294-4305, ISSN: 0305-1048 IF: 11.6

Liu B#, Shadrin A#, Sheppard C, Mekler V, Xu Y, Severinov K, Matthews S, Wigneshweraraj S, 2014, The sabotage of the bacterial transcription machinery by a small bacteriophage protein., Bacteriophage, Vol: 4, ISSN: 2159-7073

Berry AA, Yang Y, Pakharukova N, Garnett JA, Lee W-C, Cota E, Marchant J, Roy S, Tuittila M, Liu B, Inman KG, Ruiz-Perez F, Mandomando I, Nataro JP, Zavialov AV, Matthews S, 2014, Structural Insight into Host Recognition by Aggregative Adherence Fimbriae of Enteroaggregative Escherichia coli, PLOS PATHOGENS, Vol: 10, ISSN: 1553-7366 IF: 6.6

Wang K, Liu T, Lin R, Liu B, Yang G, Bu X, Wang W, Zhang P, Zhou L, Zhang J, 2014, Preparation and in vitro release of buccal tablets of naringenin-loaded MPEG-PCL nanoparticles, RSC ADVANCES, Vol: 4, Pages: 33672-33679, ISSN: 2046-2069 IF: 3

Tabib-Salazar A#, Liu B#, Doughty P, Lewis RA, Ghosh S, Parsy M-L, Simpson PJ, O'Dwyer K, Matthews SJ, Paget MS, 2013, The actinobacterial transcription factor RbpA binds to the principal sigma subunit of RNA polymerase, NUCLEIC ACIDS RESEARCH, Vol: 41, Pages: 5679-5691, ISSN: 0305-1048 IF: 11.6

Muniz-Feliciano L, Van Grol J, Portillo J-AC, Liew L, Liu B, Carlin CR, Carruthers VB, Matthews S, Subauste CS, 2013, Toxoplasma gondii-Induced Activation of EGFR Prevents Autophagy Protein-Mediated Killing of the Parasite, PLOS PATHOGENS, Vol: 9, ISSN: 1553-7374 IF: 6.6

Liu B#, Garnett JA#, Lee W-C, Lin J, Salgado P, Taylor J, Xu Y, Lambert S, Cota E, Matthews S., 2012, Promoting crystallisation of the Salmonella enteritidis fimbriae 14 pilin SefD using deuterium oxide, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 421, Pages: 208-213, ISSN: 0006-291X IF: 2.5

James E, Liu M, Sheppard C, Mekler V, Camara B, Liu B, Simpson P, Cota E, Severinov K, Matthews S, Wigneshweraraj S., 2012, Structural and Mechanistic Basis for the Inhibition of Escherichia coli RNA Polymerase by T7 Gp2, MOLECULAR CELL, Vol: 47, Pages: 755-766, ISSN: 1097-2765 IF: 14.0

Camara B, Liu M, Reynolds J, Shadrin A, Liu B, Kwok K, Simpson P, Weinzierl R, Severinov K, Cota E, Matthews S, Wigneshweraraj SR, 2010, T7 phage protein Gp2 inhibits the Escherichia coli RNA polymerase by antagonizing stable DNA strand separation near the transcription start site, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 107, Pages: 2247-2252, ISSN: 0027-8424 IF: 9.7

Liu B, Sawmynaden K, Marchant J, Simpson P, Matthews S., 2009, Complete resonance assignments for the MIC2 associated protein from Toxoplasma gondii, BIOMOLECULAR NMR ASSIGNMENTS, Vol: 3, Pages: 81-83, ISSN: 1874-2718 IF: 0.8

Saouros S, Blumenschein TMA, Sawmynaden K, Marchant J, Koutroukides T, Liu B, Simpson P, Carpenter EP, Matthews SJ, 2007, High-level bacterial expression and purification of apicomplexan micronemal proteins for structural studies, PROTEIN AND PEPTIDE LETTERS, Vol: 14, Pages: 411-415, ISSN: 0929-8665 IF: 1.0

电子邮箱：bliu2018@xjtu.edu.cn

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