美国约翰霍普金斯大学医学院肖杰博士5月9日上午学术报告

发布时间:2011-05-04访问量:41设置

报告人:肖杰博士

 

Department of Biophysics and Biophysical Chemistry, JohnsHopkinsUniversitySchool of Medicine, Baltimore, MD, 21205

 

题目:   Single molecule studies of cell division and gene regulation

时间:201159日(星期一)上午900

地点: 910-609

摘要:

We bring single-molecule approaches into live cells to study the molecular mechanisms of cell division and gene regulation. We used photoactivated localization microscopy (PALM), a single molecule-based super-resolution imaging technique, to characterize the in vivo structure of the FtsZ-ring, an essential cell division apparatus, in E. coli cells. We achieved a spatial resolution of ~35 nm, an order of magnitude improvement over diffraction-limited resolution. We discovered that in addition to the expected ring-like conformation, the Z-ring of E. coli adopts a novel compressed helical conformation with variable helical length and pitch. Quantitative measurements of the width and density of the Z-ring suggest that the Z-ring is composed of a loose bundle of FtsZ protofilaments that randomly overlap with each other in both longitudinal and radial directions of the cell. Our results provide significant insight into the spatial organization of the Z-ring and open the door for further investigations of structure-function relationships and cell cycle dependent regulation of the Z-ring. In a separate study, we developed a novel strategy, Co-Translational Activation by Cleavage (CoTrAC), to monitor autoregulation of a transcription factor, λ repressor CI, in live E. coli cells at the single-molecule level. CI becomes fully functional upon co-translational cleavage from a membrane-targeted fluorescent reporter, which can be counted individually. Using this strategy, we discovered that CI activates its own expression via transcriptional bursting, the production of multiple mRNA molecules in brief, well-separated periods of time. Our results for the first time explicitly link transcriptional bursting in prokaryotes to transcription activation by a TF and suggest new molecular mechanisms for transcription activation.

 

肖杰简介

 

Education and Professional Experience

 

 

1991–1995      B.S.          NanjingUniversity, Department of Biochemistry

1995–1997      M.S.          NanjingUniversity, Department of Biochemistry                                                    

                                           Advisor: Dexu Zhu

1997-2002       Ph. D.        RiceUniversity, Department of Biochemistry and Cell Biology

                                           Advisor: Scott F. Singleton

2002-2006       Postdoc     HarvardUniversity, Department of Chemistry and Chemical Biology                                

                                           Advisor: X. Sunney Xie

2006-               Assi. Prof.  JohnsHopkinsUniversitySchool of Medicine,Department of Biophysics and Biophysical Chemistry

 

Other Experience and Professional Memberships

Referee:     Science, Proceedings of the NationalAcademy of Sciences, Biophysical Journal, Nucleic Acids Research, Journal of Physical Chemistry.

Member:     Biophysical Society, American Chemical Association, The Protein Society, American Association for the Advancement of Science

 

Honors and Awards

2010                   NSF EAGER Award

2008                   NSF Faculty CAREER Award

2008                   Basil O’Connor Starter Scholar Research Award, March of Dime

2002                   Student Research Advance Award, Biophysical Society 46th Annual Meeting

2001                   Poster and Presentation Competition, Honorable mention, Keck Annual Research Conference

2000                   Poster and Presentation Competition, 3rd place award, Keck Annual Research Conference

 

Publications

  1. Guo F, Huang T, Buss J, Coltharp C, Hensel Z, Xiao J, In vivo structure of the E. coli FtsZ-ring revealed by photoactivated Localization Microscopy (PALM), 2010, PLoS One, 5, e12680

  2. Xiao J., Single molecule imaging in live cells. Handbook of Single-molecule Biophysics, edited by van OijenA., and Hinterdorfer P, 2009, Springer, NY,

  3. Hensel Z, Xiao J., A mechanism for stochastic decision making by bacteria. ChemBioChem, 2009, 10(6):974-976.

  4. Xiao J., Elf, J., Li, G., Yu, J., Xie X. S., Imaging gene expression in living cells at the single molecule level. Single Molecules: A Laboratory Manual, edited by Selvin P., and Ta H. 2007, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

  5. Singleton SF., Roca AI., Lee AM., Xiao J., Probing the structure of RecA-DNA filaments. Advantages of a fluorescent guanine analog. Tetrahedron, 2007, 63(17):3553-3566

  6. Yu J., Xiao J., (equal contribution), Ren X., Lao K., Xie X.S., Probing gene expression in live E. coli cells: one molecule at a time. Science, 2006, 311(5767):1600-3

  7. Xiao J., Lee, A., Singleton SF. Direct evaluation of a kinetic model for RecA-mediated DNA-strand exchange: the importance of nucleic acid dynamics and entropy during homologous genetic recombination. Chembiochem. 2006, 7(8):1265-78

  8. Xiao J., Lee, A., Singleton SF. Construction and evaluation of a kinetic scheme of RecA mediated DNA strand exchange. Biopolymers. 2006, 81(6):473-96

  9. Lee A., Xiao J.,Singleton SF. Origins of sequence selectivity in homologous genetic recombination: insights from rapid kinetic probing of RecA-mediated DNA strand exchange. J Mol Biol. 2006, 360(2):343-59

  10. Xiao J., Singleton SF., Elucidating a key intermediate in homologous DNA strand exchange: structural characterization of the RecA?triple-stranded DNA complex using fluorescence resonance energy transfer. J. Mol. Biol, 2002 Jul 12;320(3):529-58

  11. Singleton SF., Xiao J., The Stretched DNA geometry of recombination and repair nucleoprotein filaments. Biopolymers, 2001-2002;61(3):145-58   

  12. Martin SR, Lu AQ, Xiao J, Kleinjung J, Beckingham K, Bayley PM., Conformational and metal-binding properties of androcam, a testis-specific calmodulin-related protein from Drosophila. Protein Science, 1999, Nov 8(11):2444-54.

 

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