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于仲波

姓名:于仲波
职称:研究员
学科方向:单分子生物学、化学生物学、药理学
研究方向:端粒的单分子化学生物学、表观遗传因子的单分子化学生物学、药物的单分子筛选
通讯地址:南开大学药学院,天津市津南区海河教育园同砚路38号,300350
电子邮件:zyu@nankai.edu.cn
教师简介:
  染色质是细胞生命的核心,在生理、病理和药理研究中处于基础地位。虽然细胞染色质的结构变化和功能调节是动态的,但是探测其在纳米精度上的实时动态分子事件极具挑战。于仲波课题组围绕染色质的结构与功能,开发了能够实时精密探测分子相互作用的单分子技术,应用到核酸蛋白互作、蛋白蛋白互作、以及干预分子互作的药物开发等领域。譬如,细胞间期Shelterin等蛋白复合体压缩染色质的端粒,保护端粒免受DNA损伤修复机制的攻击,但是,压缩的端粒也需要解压缩,从而允许发生复制、延长和转录等重大事件。 如果我们能够实时精密探测端粒压缩和解压缩的动态过程,解析其中的分子动作,就能够深入理解端粒的分子生物学机制,从而设计针对端粒分子事件的药物靶点,为衰老、肿瘤、慢性病等端粒相关疾病开发全新的药物。又如,表观遗传因子调控DNA和组蛋白的甲基化和去甲基化修饰,但是酶促反应的分子机制不明。以MLL1 PHD3-Bromo为例,我们可以运用单分子互作技术,构建PHD3-Bromo与核小体组蛋白互作的单分子反应,解析二者互作的单分子动态机制,为开发靶向药物提供单分子反应平台。
  于仲波博士本科毕业于华中科技大学同济医学院,在美国肯特州立大学获得化学博士学位,后在荷兰代尔夫特理工大学应用物理系接受生物物理的专业训练。于仲波博士在单分子生物学领域发表SCI论文21篇,其中7篇发表在JACS,4篇发表在NAR,1篇发表在PNAS,余者多发表在生物物理、生物化学和科学仪器等专业期刊上。
  于仲波课题组开放自由,专注于成员个人发展,欢迎有兴趣的同学加入。在本课题组同学们可以受到前沿的科学文献研读指导和规范的学术写作训练,学习到精致的单分子力学操控技术和流畅的数据编程分析方法,培养出独立的科学思维习惯,建立独立的解决问题能力。希望申请者开朗活泼,对科学问题具有天然的好奇心,勇于挑战科学难题,富有恒心,百折不挠,并且有较好的数理化基础,或者生物化学和分子生物学背景。

代表性论文:
1: Ma X, Zhu M, Liu J, Li X, Qu L, Liang L, Huang W, Wang J, Li N, Chen JH, Zhang W, Yu Z. Interactions between PHD3-Bromo of MLL1 and H3K4me3 Revealed by Single-Molecule Magnetic Tweezers in a Parallel DNA Circuit. Bioconjug Chem. 2019 Dec 18;30(12):2998-3006. doi: 10.1021/acs.bioconjchem.9b00665. Epub 2019 Nov 15. PMID: 31714753.
2: Li N, Wang J, Ma K, Liang L, Mi L, Huang W, Ma X, Wang Z, Zheng W, Xu L, Chen JH, Yu Z. The dynamics of forming a triplex in an artificial telomere inferred by DNA mechanics. Nucleic Acids Res. 2019 Sep 5;47(15):e86. doi: 10.1093/nar/gkz464. PMID: 31114915; PMCID: PMC6735771.
3: Selvam S, Yu Z, Mao H. Exploded view of higher order G-quadruplex structures through click-chemistry assisted single-molecule mechanical unfolding. Nucleic Acids Res. 2016 Jan 8;44(1):45-55. doi: 10.1093/nar/gkv1326. Epub 2015 Nov 30. PMID: 26626151; PMCID: PMC4705664.
4: Yu Z, Dulin D, Cnossen J, Köber M, van Oene MM, Ordu O, Berghuis BA, Hensgens T, Lipfert J, Dekker NH. A force calibration standard for magnetic tweezers. Rev Sci Instrum. 2014 Dec;85(12):123114. doi: 10.1063/1.4904148. PMID: 25554279.
5: Yu Z, Cui Y, Selvam S, Ghimire C, Mao H. Dissecting cooperative communications in a protein with a high-throughput single-molecule scalpel. Chemphyschem. 2015 Jan 12;16(1):223-32. doi: 10.1002/cphc.201402443. Epub 2014 Dec 2. PMID: 25470139.
6: Lipfert J, Skinner GM, Keegstra JM, Hensgens T, Jager T, Dulin D, Köber M, Yu Z, Donkers SP, Chou FC, Das R, Dekker NH. Double-stranded RNA under force and torque: similarities to and striking differences from double-stranded DNA. Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15408-13. doi: 10.1073/pnas.1407197111. Epub 2014 Oct 13. PMID: 25313077; PMCID: PMC4217419.
7: Ghimire C, Park S, Iida K, Yangyuoru P, Otomo H, Yu Z, Nagasawa K, Sugiyama H, Mao H. Direct quantification of loop interaction and π-π stacking for G-quadruplex stability at the submolecular level. J Am Chem Soc. 2014 Nov 5;136(44):15537-44. doi: 10.1021/ja503585h. Epub 2014 Oct 22. PMID: 25296000.
8: Selvam S, Koirala D, Yu Z, Mao H. Quantification of topological coupling between DNA superhelicity and G-quadruplex formation. J Am Chem Soc. 2014 Oct 8;136(40):13967-70. doi: 10.1021/ja5064394. Epub 2014 Sep 23. PMID: 25216033.
9: Yu Z, Selvam S, Mao H. Intermediates stabilized by tryptophan pairs exist in trpzip Beta-hairpins. Biochemistry. 2014 Sep 30;53(38):5978-86. doi: 10.1021/bi500194g. Epub 2014 Sep 17. PMID: 25164564.
10: Dhakal S, Cui Y, Koirala D, Ghimire C, Kushwaha S, Yu Z, Yangyuoru PM, Mao H. Structural and mechanical properties of individual human telomeric G-quadruplexes in molecularly crowded solutions. Nucleic Acids Res. 2013 Apr 1;41(6):3915-23. doi: 10.1093/nar/gkt038. Epub 2013 Feb 8. PMID: 23396442; PMCID: PMC3616730.
11: Yu Z, Koirala D, Cui Y, Easterling LF, Zhao Y, Mao H. Click chemistry assisted single-molecule fingerprinting reveals a 3D biomolecular folding funnel. J Am Chem Soc. 2012 Aug 1;134(30):12338-41. doi: 10.1021/ja303218s. Epub 2012 Jul 24. PMID: 22799529.
12: Dhakal S, Lafontaine JL, Yu Z, Koirala D, Mao H. Intramolecular folding in human ILPR fragment with three C-rich repeats. PLoS One. 2012;7(6):e39271. doi: 10.1371/journal.pone.0039271. Epub 2012 Jun 25. PMID: 22761750; PMCID: PMC3382603.
13: Dhakal S, Yu Z, Konik R, Cui Y, Koirala D, Mao H. G-quadruplex and i-motif are mutually exclusive in ILPR double-stranded DNA. Biophys J. 2012 Jun 6;102(11):2575-84. doi: 10.1016/j.bpj.2012.04.024. Epub 2012 Jun 5. PMID: 22713573; PMCID: PMC3368138.
14: Yangyuoru PM, Dhakal S, Yu Z, Koirala D, Mwongela SM, Mao H. Single-molecule measurements of the binding between small molecules and DNA aptamers. Anal Chem. 2012 Jun 19;84(12):5298-303. doi: 10.1021/ac300427d. Epub 2012 Jun 1. PMID: 22702719.
15: Yu Z, Gaerig V, Cui Y, Kang H, Gokhale V, Zhao Y, Hurley LH, Mao H. Tertiary DNA structure in the single-stranded hTERT promoter fragment unfolds and refolds by parallel pathways via cooperative or sequential events. J Am Chem Soc. 2012 Mar 21;134(11):5157-64. doi: 10.1021/ja210399h. Epub 2012 Mar 9. PMID: 22372563; PMCID: PMC3336359.
16: Koirala D, Mashimo T, Sannohe Y, Yu Z, Mao H, Sugiyama H. Intramolecular folding in three tandem guanine repeats of human telomeric DNA. Chem Commun (Camb). 2012 Feb 14;48(14):2006-8. doi: 10.1039/c2cc16752b. Epub 2012 Jan 11. PMID: 22234724.
17: Koirala D, Yu Z, Dhakal S, Mao H. Detection of single nucleotide polymorphism using tension-dependent stochastic behavior of a single-molecule template. J Am Chem Soc. 2011 Jul 6;133(26):9988-91. doi: 10.1021/ja201976r. Epub 2011 Jun 9. PMID: 21639132.
18: Dhakal S, Schonhoft JD, Koirala D, Yu Z, Basu S, Mao H. Coexistence of an ILPR i-motif and a partially folded structure with comparable mechanical stability revealed at the single-molecule level. J Am Chem Soc. 2010 Jul 7;132(26):8991-7. doi: 10.1021/ja100944j. PMID: 20545340; PMCID: PMC3145834.
19: Schonhoft JD, Bajracharya R, Dhakal S, Yu Z, Mao H, Basu S. Direct experimental evidence for quadruplex-quadruplex interaction within the human ILPR. Nucleic Acids Res. 2009 Jun;37(10):3310-20. doi: 10.1093/nar/gkp181. Epub 2009 Mar 25. PMID: 19324891; PMCID: PMC2691825.
20: Yu Z, Schonhoft JD, Dhakal S, Bajracharya R, Hegde R, Basu S, Mao H. ILPR G-quadruplexes formed in seconds demonstrate high mechanical stabilities. J Am Chem Soc. 2009 Feb 11;131(5):1876-82. doi: 10.1021/ja806782s. PMID: 19154151.


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    • 地址:天津市海河教育园区同砚路38号        版权所有  南开大学药学院        访问量 155707