梁晶丹 - 教师 - 上海交通大学分子微生物学研究室

研究人员

梁晶丹

副研究员
DNA 大分子硫修饰
Email: jdliang@sjtu.edu.cn

联系方式：

办公室：徐汇校区哲生馆（原科学馆）206室

电话：021-62932943-2061(O)
传真：021-62932418

梁晶丹，女，博士，上海交通大学，生命科学技术学院，微生物代谢国家重点实验室，副研究员.

        生命的过程需要能量。有氧代谢，或者说呼吸是生物高效提取能量的方法。有氧呼吸不可避免地代谢产生超氧阴离子。超氧阴离子在超氧化物歧化酶的催化下产生过氧化氢。过氧化氢又会产生羟基自由基。
       超氧阴离子、羟基自由基等活性氧，具有活跃的氧化性，可以造成脂过氧化、蛋白质氧化及DNA氧化损伤。对生物大分子造成氧化损伤，导致衰老和疾病。生物进化出多种机制清除活性氧。
        我们发现细菌有对DNA进行硫修饰的能力。DNA的硫修饰赋予了DNA还原的化学性质，可与过氧化氢发生反应，保护细菌对抗活性氧的氧化损伤。
        人类的多种疾病和活性氧代谢有关。比如：癌症、心血管疾病、缺血性损伤、类风湿关节炎、糖尿病、帕金森及衰老等。在细菌中发现的DNA硫修饰，为我们提供了一个新的工具，来探测DNA氧化损伤与疾病的关系。

教育经历

2011.02-2013.02    访问学者，加州大学伯克利分校
2003.03-2007.12    博士，上海交通大学
1994.09-1997.06    硕士，南京农业大学
1990.09-1994.07    学士，山西大学

工作经历

2012.06-                 上海交通大学，硕士生导师
2011.12-                 上海交通大学微生物代谢国家重点实验室, 副研究员
2008.01-2011.12    上海交通大学，讲师
1997.06-2003.03     南通大学，助教

研究兴趣和方向：

一、硫化修饰DNA的序列选择性研究和生物学意义

DNA的磷硫酰化修饰是迄今发现的第一种DNA骨架上的生理修饰，在细菌中广泛存在。现已证实细菌DNA生理的硫化修饰丰度和频率都非常低,不同物种硫化修饰的DNA序列各不相同，具有明确的修饰序列优先选择性。生物硫化DNA的序列选择性的过程怎样发生？是何因素决定了其修饰的选择性？其特定的生物学意义等一系列科学问题需要探索。随着DNA硫化修饰的化学结构的阐明，DNA硫化修饰课题多个未解之谜，需要投入更多的人力、物力和精力进行细致深入的研究。

二、磷硫酰修饰DNA作为抑制剂的抑制机理和应用研究

目前实验数据证明硫化修饰DNA可以作为某些限制性内切酶和整合酶的抑制剂，进一步将开展其抑制的分子机制研究，设计和开发一些重要的整合酶的硫化DNA 抑制剂。

三、重要蛋白复合物结构、功能和机理研究

DNA复制复合物结合DNA的关键氨基酸的功能研究和复制过程的分子细节研究。

Figure 1 In vivo resistance of PT DNA to double-strand breakage caused by H2O2 Salmonella cells were incubated with increasing concentration of H2O2 for 2h. (Xie, et al. Nucleic Acids Res. 2012 )

Figure 2 Heterologous expression of the S. enterica serovar cerro 87 dptBCDEgenes in E. coli BW25113. (An, et al. PLoS One. 2012)

Figure 3 (A) Organization of the dnd gene cluster and in-frame deletion of dndB. (B) Enhanced Dnd phenotype displayed by dndB− mutant HXY2 as compared with that of wild-type 1326. Lack of Dnd phenotype displayed by dndA− mutant HXY1 and dnd-deletion mutant HXY6 is shown as controls. (C) Preferential cleavage at specific site of EcoRV-linearized pHZ209 originating from 1326, but more random and lack of cleavage of the same DNA originating from HXY2 and HXY6, respectively. All the samples were treated with activated Tris-buffer followed by gel electrophoresis. (Liang, et al. Nucleic Acids Res. 2007)

发表论文

1. Phosphorothioate DNA as an antioxidant in bacteria. Xie XQ*, Liang JD*, Pu TN, Xu F, Yao F, Yang Y, Zhao YL, You DL, Zhou XF, Deng ZX, Wang ZJ. Nucleic Acids Research. 2012 Oct; 40(18):9115-24. (*These authors contributed equally to this work)
2. A novel target of IscS in Escherichia coli: participating in DNA phosphorothioation. An XH, Xiong W, Yang Y, Li FH, Zhou XF, Wang ZJ, Deng ZX*, Liang JD*. PLoS One. 2012; 7(12):e51265. (*Corresponding author).
3. Effective elimination of nucleic acids from bacterial protein samples for optimized blue native polyacrylamide gel electrophoresis. Liang JD*, Niu QL*, Xu XP, Luo YM, Zhou XF, Deng ZX, Wang ZJ. Electrophoresis. 2009 Jul; 30(14):2454-9. (*These authors contributed equally to this work)
4. DNA phosphorothioation in Streptomyces lividans: Mutational analysis of the dnd locus. Xu TG*, Liang JD*, Chen S, Wang LR, He XY, You DL, Wang ZJ, Li AY, Xu ZL, Zhou XF, Deng ZX. BMC Microbiol. 2009 Feb 20; 9(1):41. (*These authors contributed equally to this work)
5. DNA modification by sulfur: analysis of the sequence recognition specificity surrounding the modification sites. Liang JD*, Wang ZJ*, He XY, Li JL, Zhou XF，Deng ZX. Nucleic Acids Research. 2007 Apr; 35(9):2944-54. (*These authors contributed equally to this work)
6. Characterization of the N-methyltransferase CalM involved in calcimycin biosynthesis by Streptomyces chartreusis NRRL 3882. Wu Q, Gou L, Lin S, Liang J, Yin J, Zhou X, Bai L, An D, Deng Z, Wang Z. Biochimie. 2013 Apr 11.
7. Mutasynthesis of Pyrrole Spiroketal Compound by Using Calcimycin 3-Hydroxy Anthranilic Acid Biosynthetic Mutant. Gou L, Wu Q, Lin S, Li X, Liang J, Zhou X, An D, Deng Z, Wang Z. Applied Microbiology and Biotechnology , 2013 May 12.
8. Characterization of the Pyrrole Polyether Antibiotic Calcimycin (A23187) Biosynthetic Gene Cluster from Streptomyces chartreusis NRRL 3882. Wu Q, Liang J, Lin S, Zhou X, Bai L , Deng Z and Wang Z. Antimicrobial Agents and Chemotherapy (AAC)，2011 Mar; 55(3):974-82.
9. Theoretical study on steric effects of DNA phosphorothioation: B-helical destabilization in Rp-phosphorothioated DNA. Zhang Y, Liang J, Lian P, Han Y, Chen Y, Bai L, Wang Z, Liang J, Deng Z, Zhao YL. J Phys Chem B.2012 Sep 6;116(35):10639-48.
10. Crystal structure of the cysteine desulfurase DndA from Streptomyces lividans which is involved in DNA phosphorothioation. Chen F, Zhang Z, Lin K, Qian T, Zhang Y, You D, He X, Wang Z, Liang J, Deng Z, Wu G. PLoS One. 2012; 7(5):e36635.
11. Structural insights into DndE from Escherichia coli B7A involved in DNA phosphorothioation modification. Hu W, Wang C, Liang J, Zhang T, Hu Z, Wang Z, Lan W, Li F, Wu H, Ding J, Wu G, Deng Z, Cao C. Cell Res.2012 Jul;22(7):1203-6.
12. Purification, crystallization and preliminary X-ray analysis of the DndE protein from Salmonella enterica serovar Cerro 87, which is involved in DNA phosphorothioation. F. Chen, K. Lin, Z. Zhang, L. Chen, X. Shi, C. Cao, Z. Wang, J. Liang, Z. Deng, G. Wu. Acta Crystallogr Sect F Struct Biol Cryst Commun.2011 Nov 1; 67(Pt 11):1440-2.
13. Two pHZ1358-derivative Vectors for Efficient Gene Knockout in Streptomyces. He, Y, Wang Z, Bai L, Liang J, Zhou X, Deng Z. J. Microbiol. Biotechnol. 2010 4; 20(4): 678-682