报告人：Wenfeng An (Currently a Postdoctoral Fellow in John Hopkings and will be a tenure track assistant professor in Washington State University, 2008)  Department of Molecular Biology & Geneticsc, Johns Hopkins University School of Medicine   时间：2007年11月14日本周三，下午2：00   地点：在生化楼3楼中厅   报告题目："Mouse models of L1 retrotransposons and applications in genome-wide mutagenesis"   欢迎广大师生聆听该讲座 （欢迎有意读博士后者） 记学分   主办： 生化与分子生物学系     报告内容摘要： Long interspersed elements type 1 (LINE-1, or L1) are common components of mammalian genomes, accounting for approximately one-fifth of the human and mouse genomes. In contrast to DNA transposons, L1s replicate in the genome by retrotransposition involving reverse transcription of an RNA intermediate. This unique, copy-and-paste mode of replication makes L1s attractive tools for genome-wide random mutagenesis in mice. However, endogenous L1 elements are inefficient in retrotransposition when introduced as transgenes. A former BJMU graduate, Dr. An did his doctoral work on retroviral recombination in University of Michigan. As part of his postdoctoral work, Dr. An has focused his efforts in developing an L1-based mutagenesis system using a synthetic L1 element, termed ORFeus. He developed a transgenic mouse model in which ORFeus was expressed from a constitutive promoter, and established definitive evidence for ORFeus retrotransposition activity both in germ line and somatic tissues. In order to achieve controlled activation of ORFeus in mice, Dr. An adopted the Cre-lox system and detected patterns of ORFeus activation consistent with the tissue specificity of individual Cre lines.Dr. An\'s current work involves further optimization of ORFeus system for under standing L1 regulation and for forward genetics based gene discovery in tumorigenesis and other diseases.   报告人简介： 1988-1993 M.D. in Health Policy and Management, Beijing Medical University, Beijing 1993-1996 M.P.H. in Epidemiology, Beijing Medical University, Beijing Advisors: Drs. Hui Zhuang & Wanfu Zhu 1998-2003 Ph.D. in Microbiology and Immunology, University of Michigan, Ann Arbor, MI, Advisor: Dr. Alice Telesnitsky 2003-2008 Postdoctoral Fellow, Department of Molecular Biology & Genetics and The High Throughput Biology Center, Johns Hopkins University Advisor: Dr. Jef D. Boeke   Recent publications: 1. An, W. & Telesnitsky, A. Frequency of direct repeat deletion in a human immunodeficiency virus type 1 vector during reverse transcription in human cells. Virology 286, 475-82. (2001). 2. An, W. & Telesnitsky, A. Effects of varying sequence similarity on the frequency of repeat deletion during reverse transcription of a human immunodeficiency virus type 1 vector. J Virol 76, 7897-902. (2002). 3. An, W. & Telesnitsky, A. HIV-1 genetic recombination: experimental approaches and observations. AIDS Rev 4, 195-212. (2002). 4. Onafuwa, A., An, W ., Robson, N.D. & Telesnitsky, A. Human immunodeficiency virus type 1 genetic recombination is more frequent than that of Moloney murine leukemia virus despite similar template switching rates. J Virol 77, 4577-87. (2003). 5. An, W. & Telesnitsky, A. Human immunodeficiency virus type 1 transductive recombination can occur frequently and in proportion to polyadenylation signal readthrough. J Virol 78, 3419-28 (2004). 6. Flynn, J.A., An, W., King, S.R. & Telesnitsky, A. Nonrandom dimerization of murine leukemia virus genomic RNAs. J Virol 78, 12129-39 (2004). 7. An, W. & Boeke, J.D. Transposon technology and vertebrate functional genomics. Genome Biol 6, 361 (2005). 8. An, W., Han, J.S., Wheelan, S.J., Davis, E.S., Coombes, C.E., Ye, P., Triplett, C. & Boeke,J.D. Active retrotransposition by a synthetic L1 element in mice. Proc Natl Acad Sci U S A 103, 18662-7 (2006). 9. Boeke, J.D., An, W., Dai, L., Davis, E.S, Han, J.S., O’Donnell, K.A., Scheifele, L.Z. & Wheelan, S.J. Retrotransposons–natural and synthetic. in Retrotransposition, Diversity and the Brain (eds. Gage, F.H. & Christen, Y.) 21-32 (Springer-Verlag Berlin Heidelberg, 2007). 10. An, W., Han, J.S., Schrum, C.M., Maitra, A., Koentgen, F. & Boeke, J.D. Controlled activation of a single-copy L1 transgene in mice by Cre recombinase. Submitted.