演讲嘉宾

吴 强


上海交通大学教授

会议报告摘要:CRISPR基因组DNA片段编辑

源于细菌和古菌的Ⅱ型成簇常间隔短回文重复系统(CRISPR/Cas9)近年被改造成为基因组定点编辑的新技术。由于它具有设计简单、操作方便、费用低廉等巨大优势,给遗传操作这一领域带来了一场革命性的改变。我将重点介绍CRISPR/Cas9系统在DNA片段编辑方面的研究和应用,主要包括DNA片段的删除、反转、重复、插入和易位。DNA片段编辑方法为研究基因功能、调控元件、组织发育和疾病发生发展以及染色质架构和结构变异提供了有力手段,我将汇报我们在基因组DNA片段编辑的研究进展


研究方向

长期从事复杂基因家族的表达调控和在体功能研究,使用分子生物学和计算生物学方法,首次发现了五十多个原钙粘蛋白(protocadherin)新基因,并阐明了原钙粘蛋白基因族(protocadherin gene family)基因组结构的内在规律。发现并开拓了AT-AC内含子剪接领域,阐明了多种第一外显子调控复杂基因家族细胞和组织特异性表达的机理;发现了尿苷二磷酸葡醛酸转移酶(Ugt)基因簇具有类似于原钙粘蛋白基因簇的基因组结构;系统地分析了原钙粘蛋白和Ugt基因谱系的表达模式;发现了原钙粘蛋白和Ugt基因簇在脊椎动物进化的分子多样性的自适性选择;建立了近二十个原钙粘蛋白基因敲除小鼠品系,开发了基于跨等位基因重组的基因簇多基因打靶的新技术方法。研究论文先后发表于Science, Cell, PNAS, Molecular Cell, Nature Genetics等期刊上。


研究经历

上海交通大学特聘教授,博士生导师,系统生物医学教育部重点实验室常务副主任,上海交通大学比较生物医学中心主任,科技部重大科学研究计划项目首席科学家,上海市浦江学者,中美生命科学家学会终身会员,享受政府特殊津贴。生物化学与生物物理学报 (Acta Biochimica et Biophysica Sinica),Editor;中国神经科学学会;the Chinese Society for Neuroscience,会员;The Society for Neuroscience,正式会员;The RNA Society,会员;The American Association for the Advancement of Sciences,会员;The Sigma Xi Scientific Research Society,会员;The American Society of Human Genetics,会员;The Society of Chinese Bioscientists in America,终身会员。


近期发表论文

  1. Huang, H. and Wu, Q. (2016). CRISPR Double Cutting through the Labyrinthine Architecture of 3D Genomes. J Genet Genomics. 43: 273-288. Invited Review.
  2. Guo, Y., Q. Xu, D. Canzio, J. Shou, J. Li, D.U. Gorkin, I. Jung, H. Wu, Y. Zhai, Y. Tang, Y. Lu, Y. Wu, Z. Jia, W. Li, M.Q. Zhang, B. Ren, A.R. Krainer, T. Maniatis, Wu Q. (2015). CRISPR inversion of CTCF sites alters genome topology and enhancer/promoter function. Cell 162: 900-910.doi:10.1016/j.cell.2015.07.038. CELL Hottest Article. Research Highlighted in Cell, 162, 703–705; Nature Reviews Molecular Cell Biology 16, 578–579.
  3. Li J, Shou J,Guo Y, Tang Y, Wu Y, Jia Z, Zhai Y, Chen Z, Xu Q, Wu, Q. (2015). Efficient inversions and duplications of mammalian regulatory DNA elements and gene clusters by CRISPR/Cas9. J. Mol. Cell. Biol. 7: 284-298. Cover Article.
  4. Jia Z, Guo Y, Tang Y, Xu Q, Li B, Wu Q. (2014) Regulation of the protocadherin Celsr3 gene and its role in globus pallidus development and connectivity.Mol Cell Biol. 34: 3895-3910.
  5. Wang Y., Huang H., Wu Q. (2014) Characterization of the zebrafish Ugt repertoire reveals a new class of drug-metabolizing UDP glucuronosyltransferases.Mol. Pharmacol. 86: 62-75.
  6. Guo Y., Monahan K., Wu H., Varley KE., Gertz J., Li W., Myers RM., Maniatis T., Wu Q. (2012) CTCF/Cohesin-mediated DNA Looping is required for protocadherin alpha promoter choice. Proc Natl Acad Sci USA 109: 21081-21086.
  7. Suo L., Lu H., Ying G., Capecchi M.R., Wu, Q. (2012) Protocadherin clusters and cell adhesion kinase regulate dendrite complexity through Rho GTPase. J Mol Cell Biol 4: 362-376. Cover Article
  8. Huang H. and Wu, Q*. (2010). Cloning and comparative analyses of the zebrafish Ugt repertoire reveal its evolutionary diversity. PLoS ONE 5: E9144.
  9. Ying,G., Wu, S., Hou, R., Huang, W., Capecchi, M., Wu, Q*. (2009). Protocadherin Celsr3 is required for interneuron migration in the mouse forebrain. Molecular and Cellular Biology 29:3045-3061.
  10. Wu, S., Ying, G., Wu, Q., and Capecchi, M.R. (2008). A protocol for constructing gene targeting vectors: generating knockout mice for the cadherin family and beyond. Nature Protocol 3:1056-1076.
  11. Zou, C., Huang, W., Ying, G., and Wu, Q*. (2007). Sequence analysis and expression mapping of the rat clustered protocadherin gene repertoires. Neuroscience 144: 579-603.
  12. Wu, S., Ying, G., Wu, Q., and Capecchi, M.R. (2007). Towards simpler and faster genome-wide mutagenesis in mice. Nature Genetics 39: 922-930.
  13. Li, C. and Wu, Q*. (2007). Evolution of vertebrate multiple variable first exons and structural diversity of drug metabolizing enzymes. BMC Evolutionary Biology 7: 69.