窦硕星

简介


       男,1966年3月生。1985年毕业于山东大学光学系;1988年7月于山东大学晶体材料研究所获硕士学位;1992年11月于法国居里大学(巴黎六大)获理学博士学位。1995年—2001年,中国科学院物理研究所副研究员。曾先后在法国、德国和韩国进行高访研究。现任中国科学院物理研究所研究员、国科大教授、博士生导师、软物质物理实验室SM1组课题组长。
                    

主要研究方向


       复杂系统和生物大分子动力学。目前我们的研究课题主要包括:(1)DNA解旋酶等生物马达蛋白运动机理;(2)细胞内生物大分子的扩散与运输;(3)染色质动态结构和调控的分子机制;(4)抗癌药物与DNA、活细胞的相互作用。
                 

过去的主要工作及获得的成果


       1985年至2001年,主要从事非线性光学、微腔激光等方面的研究。2002年开始从事物理学与生命科学交叉领域研究,主要工作包括:RecQ、BLM、PcrA等多种不同DNA解旋酶的生物学特性及其对双链DNA、G四联体的解旋机理;G三联体、四联体的折叠动力学;DNA与组蛋白的相互作用;抗癌药物顺铂、奥沙利铂、反铂诱导的DNA凝聚过程;活细胞内分子运输的动力学特性以及早期凋亡细胞的胞内运输加速现象;驱动蛋白的运动机理等。在 J. Am. Chem. Soc.、Nucleic Acids Research、PNAS、Phys. Rev. Lett.、Structure、Biochem. J.、J. Biol. Chem.、Sci. Rep.、Phys. Rev. E、Appl. Phys. Lett.、Opt. Lett.、J. Opt. Soc. Am. B、Opt. comm. 等杂志上发表论文120余篇。
                 

代表性论文及专利


  1. W.-F. Chen, S. Rety, H.-L. Guo, Y.-X. Dai, W.-Q. Wu, N.-N. Liu, D. Auguin, Q.-W. Liu, X.-M. Hou, S.-X. Dou, and X.-G. Xi, “Molecular mechanistic insights into Drosophila DHX36-mediated G-quadruplex unfolding: A structure-based model.” Structure 26, 403-415 (2018).
  2. B. Li, S.-X. Dou, J.-W. Yuan, Y.-R. Liu, W. Li, F. F. Ye, P.-Y. Wang, and H. Li, “Intracellular transport is accelerated in early apoptotic cells.” Proc. Natl. Acad. Sci. U.S.A. 115, 12118-12123 (2018).
  3. X.-M. Lu, H. Li, J. You, W. Li, P.-Y. Wang, M. Li, S.-X. Dou, and X.-G. Xi, “Folding dynamics of parallel and antiparallel G-triplexes under the influence of proximal DNA.” J. Phys. Chem. B 122, 9499-9506 (2018).
  4. K.-Y. Lu, W.-F. Chen, S. Rety, N.-N. Liu, W.-Q. Wu, Y.-X. Dai, D. Li, H.-Y. Ma, S.-X. Dou, and X.-G. Xi, “Insights into the structural and mechanistic basis of multifunctional S. cerevisiae Pif1p helicase.” Nucleic Acids Res. 46, 1486-1500 (2018).
  5. J. You, H. Li, X.-M. Lu, W. Li, P.-Y. Wang, S.-X. Dou, and X.-G. Xi, “Effects of monovalent cations on folding kinetics of G-quadruplexes.” Bioscience Reports 37, BSR20170771 (2017).
  6. W. X. Lin, J. B. Ma, D. G. Nong, C. H. Xu, B. Zhang, J. H. Li, Q. Jia, S. X. Dou, F. F. Ye, X. G. Xi, Y. Lu, and M. Li, “Helicase stepping investigated with one-nucleotide resolution fluorescence resonance energy transfer.” Phys. Rev. Lett. 119, 138102 (2017).
  7. W.-Q. Wu, X.-M. Hou, B. Zhang, P. Fossé, B. René, O. Mauffret, M. Li, S.-X. Dou, and X.-G. Xi, “Single-molecule studies reveal reciprocating of WRN helicase core along ssDNA during DNA unwinding.” Scientific Reports 7, 43954 (2017).
  8. W.-F. Chen, Y.-X. Dai, X.-L. Duan, N.-N. Liu, W. Shi, N. Li, M. Li, S.-X. Dou, Y.-H. Dong, S. Rety, and X.-G. Xi, Crystal structures of the BsPif1 helicase reveal that a major movement of the 2B SH3 domain is required for DNA unwinding. Nucleic Acids Res. 44, 2949-2961 (2016).
  9. B. Zhang, W.-Q. Wu, N.-N. Liu, X.-L. Duan, M. Li, S.-X. Dou, X.-M. Hou, and X.-G. Xi, “G-quadruplex and G-rich sequence stimulate Pif1p-catalyzed downstream duplex DNA unwinding through reducing waiting time at ss/dsDNA junction.” Nucleic Acids Res. 44, 8385-8394 (2016).
  10. J.-H. Li, W.-X. Lin, B. Zhang, D.-G. Nong, H.-P. Ju, J.-B. Ma, C.-H. Xu, F.-F. Ye, X.-G. Xi, M. Li, Y. Lu, and S.-X. Dou, “Pif1 is a force-regulated helicase.” Nucleic Acids Res. 44, 4330-4339 (2016).
  11. H.-P. Ju, Y.-Z. Wang, J. You, X.-M. Hou, X.-G. Xi, S.-X. Dou, W. Li, and P.-Y. Wang, “Folding kinetics of single human telomeric G-quadruplex affected by cisplatin.” ACS Omega 1, 244-250 (2016).
  12. Y.-W. Zhang, D.-G. Nong, S.-X. Dou, W. Li, Y. Yan, X.-G. Xi, C.-H. Xu, and M. Li, “Iterative homology checking and non-uniform stepping during RecA-mediated strand exchange.” Biochem. Biophys. Res. Commun. 478, 1153e1157 (2016).
  13. N.-N. Liu, X.-L. Duan, X. Ai, Y.-T. Yang, M. Li, S.-X. Dou, S. Rety, E. Deprez, and X.-G. Xi, “The Bacteroides sp. 3_1_23 Pif1 protein is a multifunctional helicase.” Nucleic Acids Res. 43, 8942-8954 (2015).
  14. Y. R. Liu, P. Xie, P. Y. Wang, M. Li, H. Li, W. Li, and S.-X. Dou, “A model for chromosome organization during the cell cycle in live E. coli.” Scientific Reports 5, 17133 (2015).
  15. W.-Q. Wu, X.-M. Hou, M. Li, S.-X. Dou, and X.-G. Xi, “BLM unfolds G-quadruplexes in different structural environments through different mechanisms.” Nucleic Acids Res. 43, 4614-4626 (2015).
  16. X.-L. Duan, N.-N. Liu, Y.-T. Yang, H.-H. Li, M. Li, S.-X. Dou, and X.-G. Xi, “G-quadruplexes significantly stimulate Pif1 helicase-catalyzed duplex DNA unwinding.” J. Biol. Chem. 290, 7722-7735 (2015).
  17. S. Wang, W. Qin, J.-H. Li, Y. Lu, K.-Y. Lu, D.-G. Nong, S.-X. Dou, C.-H. Xu, X,-G. Xi, and M. Li, “Unwinding forward and sliding back: an intermittent unwinding mode of the BLM helicase.” Nucleic Acids Res. 43, 3736-3746 (2015).
  18. X.-M. Hou, W.-Q. Wu, X.-L. Duan, N.-N. Liu, H.-H. Li, J. Fu, S.-X. Dou, M. Li, and X.-G. Xi, “Molecular mechanism of G-quadruplex unwinding helicase: sequential and repetitive unfolding of G-quadruplex by Pif1 helicase.” Biochem. J. 466, 189-199 (2015).
  19. H. Li, S.-X. Dou, Y.-R. Liu, W. Li, P. Xie, W.-C. Wang, and P.-Y. Wang. “Mapping intracellular diffusion distribution using single quantum dot tracking: compartmentalized diffusion defined by endoplasmic reticulum.” J. Am. Chem. Soc. 137, 436-444 (2015).
  20. H.-Y. Zhang, L.-Y. Zhang, W.-C. Wang, P. Xie, S.-X. Dou, C. Ji, W. Li, Y.-R. Liu, and P.-Y. Wang. “Oxaliplatin and its enantiomer induce different condensation dynamics of single DNA molecules.” PLOS ONE 8, e71556 (2013).
  21. Y.-R. Liu, S.-X. Dou, C. Ji, W.-C. Wang, P. Xie, H.-Y. Zhang, and P.-Y. Wang. “Transplatin enhances effect of cisplatin on both single DNA molecules and live tumor cells.” Archives Biochem. Biophys. 536, 12-24 (2013).
  22. H. Li, Z. W. Duan, P. Xie, Y. R. Liu, W. C. Wang, S.-X. Dou, and Y.-P. Wang. “Effects of paclitaxel on EGFR endocytic trafficking revealed using quantum dot tracking in single cells.” PLOS ONE 7, e45465 (2012).
  23. Y.-N. Xu, N. Bazeille, X.-Y. Ding, X.-M. Lu, P.-Y. Wang, E. Bugnard, V. Grondin, S.-X. Dou, and X.-G Xi, “Multimeric BLM is dissociated upon ATP hydrolysis and functions as monomers in resolving DNA structures.” Nucleic Acids Res. 40, 9802-9814 (2012).
  24. W. Li, Z. Q. Sun, P. Xie, S.-X. Dou, W. C. Wang, and P.-Y. Wang, “Elastic response and length change of single DNA molecules induced by a combination of cisplatin and transplatin.” Phys. Rev. E 85, 021918 (2012).
  25. S.-X. Dou and X.-G. Xi, “Fluorometric assays for characterizing DNA helicases.” Methods 51, 295-302 (2010).
  26. B.-Y. Pan, S.-X. Dou, Y. Yang, Y.-N. Xu, E. Bugnard, X.-Y. Ding, L. Zhang, P.-Y. Wang, M. Li, and X.-G. Xi, “Mutual inhibition of RecQ molecules in DNA unwinding.” J. Biol. Chem. 285, 15884-15893 (2010).
  27. Y. Yang, S.-X. Dou, Y.-N. Xu, P.-Y. Wang, P. Rigolet, H.-Q. Xu, and X.-G. Xi, “Kinetic mechanism of DNA unwinding by the BLM helicase core and molecular basis for its low processivity.” Biochemistry 49, 656-668 (2010).
  28. X.-M. Hou, X.-H. Zhang, K.-J. Wei, C. Ji, S.-X. Dou, W.-C. Wang, M. Li, P.-Y. Wang, “Cisplatin induces loop structures and condensation of single DNA molecules.” Nucleic Acids Res. 37, 1400-1410 (2009).
  29. B.-Y. Pan, L. Zhang, S.-X. Dou, and P.-Y. Wang, “Forces-induced pinpoint denaturation of short DNA.” Biochem. Biophys. Res. Commun. 388, 137-140 (2009).
  30. X.-M. Hou, W. Li, S.-X. Dou, L.-Y. Zhang, P. Xie, W.-C Wang, P.-Y. Wang, “Formation of DNA toroids inside confined droplets adsorbed on mica surfaces.” Phys. Rev. E 79, 051912 (2009).
  31. B. Sun, K.-J. Wei, B. Zhang, X.-H. Zhang, S.-X. Dou, M. Li, X.-G. Xi, “Impediment of E. coli UvrD by DNA-destabilizing force reveals a strained-inchworm mechanism of DNA unwinding.” EMBO J. 27, 3279-3287 (2008).
  32. Y. Yang, S.-X. Dou, H. Ren, P.-Y. Wang, X.-D. Zhang, M. Qian, B.-Y. Pan, X.-G. Xi,Evidence for a functional dimeric form of the PcrA helicase in DNA unwinding.” Nucleic Acids Res. 36, 1976-1989 (2008).
  33. H. Ren, S.-X. Dou, X.-D. Zhang, P.-Y. Wang, R. Kanagaraj, J.-L. Liu, P. Janscak, J.-S. Hu, X.-G. Xi, “The zinc-binding motif of human RECQ5β suppresses the intrinsic strand-annealing activity of its DExH helicase domain and is essential for the helicase activity of the enzyme.” Biochem. J. 412, 425-433 (2008).
  34. H. Ren, S.-X. Dou, P. Rigolet, Y. Yang, P.-Y. Wang, M. Amor-Gueret, X.-G. Xi, “The arginine finger of the Bloom syndrome protein: its structural organization and its role in energy coupling.” Nucleic Acids Res. 35, 6029-6041 (2007).
  35. R.-B. Guo, P. Rigolet, H. Ren, B. Zhang, X.-D. Zhang, S.-X. Dou, P.-Y. Wang, M. Amor-Gueret, X.-G. Xi, “Structural and functional analyses of disease-causing missense mutations in Bloom syndrome protein.” Nucleic Acids Res. 35, 6297-6310 (2007).
  36. W. Li, S.-X. Dou, P. Xie, P.-X. Wang, “Brownian dynamics simulation of the effect of histone modification on nucleosome structure.” Phys. Rev. E 75, 051915 (2007).
  37. W. Li, S.-X. Dou, P. Xie, P.-Y. Wang, “Browinan dynamics simulation of directional sliding of histone octamers caused by DNA bending.” Phys. Rev. E 73, 051909 (2006).
  38. X.-D. Zhang, S.-X. Dou, P. Xie, J. S. Hu, P.-Y. Wang, X.-G. Xi, “E. coli RecQ is a rapid, efficient and monomeric helicase.” J. Biol. Chem. 281, 12655-12663 (2006).
  39. X.-D. Zhang, S.-X. Dou, P. Xie, P.-Y. Wang, X.-G. Xi, “RecQ helicase-catalyzed DNA unwinding detected by fluorescence resonance energy transfer.” Acta Biochimi. Biophys. Sin. 37, 593-600 (2005).
  40. J. L. Liu, P. Rigolet, S.-X. Dou, P.-Y. Wang, X.-G. Xi, “The Zinc finger motif of Escherichia coli RecQ is implicated in both DNA binding and protein folding.” J. Biol. Chem. 279, 42794-42802 (2004).
  41. S.-X. Dou, P.-Y. Wang, H.-Q. Xu, X.-G. Xi, “The DNA binding properties of the Escherichia coli RecQ helicase.” J. Biol. Chem. 279, 6354-6363 (2004).
  42. Y.-Y. Liu, P.-Y. Wang, S.-X. Dou, W.-C. Wang, P. Xie, H.-W. Yin, X.-D. Zhang, X.-G. Xi, “Ionic effect on combing of single DNA molecules and observation of their force-induced melting by fluorescence microscopy.” J. Chem. Phys. 121, 4302-4309 (2004).

目前的研究课题及展望


       复杂系统和生物大分子动力学是国际上受到普遍关注的物理与生物学交叉的前沿研究领域,也是软凝聚态物理的一个重要研究方向。目前,我们主要致力于从生物大分子以及活细胞的层次去研究生命过程以及外来分子(如抗癌药物)对生命过程的影响,所开展的上述研究课题属于国际上的研究热点。分子生物物理和生物化学学科的研究已由传统方法发展到能够对单分子实行直接的操纵与测量。应用现代物理学和物理化学的新手段和新方法,理论与实验相结合,对一些重要的生物大分子、药物分子及其相互作用的研究,有助于从分子水平上揭示生物大分子结构、运动与功能的关系以及药物的作用机理。 
       在实验研究方面,我们已拥有了一些重要的研究设备,包括用于活细胞研究的荧光显微系统(荧光纳米粒子追踪技术)、单分子操纵设备(磁镊)、单分子荧光显微装置、单分子荧光显微/磁镊复合装置、Stopped-flow快速反应动力学系统、原子力显微镜、生物样品制备、纯化和表征设备(wet lab)。另外,我们与国内外生物学家建立了广泛、长期、良好的合作关系,为有关研究工作的顺利开展奠定了坚实的基础。
               

培养研究生情况


       已培养(包括联合培养)博士、硕士研究生11名。欢迎来自物理、化学、生物专业的有志青年学子加入我们的研究队伍,共同探索生命的奥秘、见证生命的神奇!
            

电话:

010-82649484

Email

sxdou@iphy.ac.cn