鲍时来，博士，研究员，博士生导师。
1988年获安徽农学院学士学位，1993年获中国科学技术大学硕士学位，1999年获中国科学技术大学博士学位，1999－2005年先后在美国普渡大学作访问学者和德克萨斯大学安德森癌症研究中心从事博士后研究，2003年回到中国科学院遗传研究所工作。实验室研究方向是细胞器高尔基体发生和表观遗传。
主要研究内容
（一）揭示细胞器高尔基体结构和功能在个体发育和疾病发生中的作用
真核细胞的高尔基体（Golgi Apparatus）是分泌途径最重要的细胞器，其结构和功能影响细胞内蛋白质等物质的翻译后修饰、折叠和运输。但是高尔基体结构功能缺陷对个体发育和疾病发生的作用目前还不清楚。本课题组的研究重点一是揭示蛋白质甲基化修饰对细胞分泌途径细胞器，特别是高尔基体结构和功能的调控作用。我们利用蛋白质组学方法，研究蛋白质甲基转移酶与高尔基体基质蛋白等蛋白质复合体之间的相互作用，以阐明蛋白质甲基化修饰的作用机理。同时，我们通过建立小鼠Knockout模型，阐明高尔基体结构和功能在调控动物个体发育和疾病发生中的作用。
（二）研究淋巴细胞分化和儿童淋巴细胞白血病发生的表观遗传机制
造血干细胞（HSC）向淋巴细胞分化过程决定于V（D）J重组和基因的准确转录。这些过程受组蛋白修饰等表观遗传因素的调控。淋巴细胞分化过程不正常就会导致许多疾病的发生，严重的会发生白血病。在儿童时期主要发生淋巴细胞白血病。我们主要研究组蛋白精氨酸甲基化修饰在造血干细胞向淋巴细胞分化中的作用机制。我们与北京儿童医院合作，研究蛋白质甲基化修饰与儿童白血病发生之间的对应关系。通过建立小鼠转基因和Knockout模型，揭示组蛋白精氨酸甲基化等表观遗传修饰调控淋巴细胞分化和儿童白血病发生的作用机理。
（三）揭示调控基因转录和个体发育的“组蛋白密码”
个体发育和细胞分化过程决定于基因的差异表达。基因的表达与否决定于染色质结构。基因转录表达和沉默就是染色质的重塑过程。组蛋白甲基化、乙酰化、磷酸化和DNA甲基化等表观遗传修饰协同作用，调控染色质重塑过程。调控个体发育的基因同时受到多种组蛋白表观遗传修饰调控，那么决定基因转录和个体发育的组蛋白密码（histone code）是什么目前还不够清楚。我们主要利用模式植物拟南芥有大量可以存活的突变体，利用遗传和生化等方法，研究调控植物开花时间的“组蛋白密码”组成、分子识别和信号传导机理。
近年发表的代表性论文:（＃为通信作者）
1. Guo S, and Bao S#. (2010) srGAP2 arginine methylation regulates cell migration and cell spreading through promoting of dimerization. J Biol Chem. (accepted)
2. Jiang Y, Wang X, Bao S, Guo R, Johnson D, Shen X, Li L. (2010) The INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway. PNAS (accepted)
3. Zhou, Z*., Sun, X*., Zou, Z., Sun, L., Zhang, T., Guo, S., Wen, Y., Liu, L., Wang, Y., Qin, J., Li, L., Gong, W., and Bao, S#. (2010) PRMT5 regulates Golgi apparatus structure through methylation of the golgin GM130. Cell Research, in press.
4. Ren, J., Wang, Y., Liang, Y., Zhang, Y., Bao, S. and Xu, Z. (2010). Methylation of ribosomal protein s10 by protein arginine methyltransferase 5 regulates ribosome biogenesis. J Biol Chem.285, 12695-12705.
5. Li, Z, Zhang, W., Wu, M., Zhu, S., Gao, C., Sun, L., Zhang, R., Qiao, N., Xue, H., Hu, Y., Bao, S#, Zheng, H#. and Han, J.D#. (2009) Gene expression-based classification and regulatory networks of pediatric acute lymphoblastic leukemia. Blood, 114, 4486-4493.
6. Liu, R., Strom, A. L., Zhai, J., Gal, J., Bao, S., Gong, W., and Zhu, H. (2009). Enzymatically inactive adenylate kinase 4 interacts with mitochondrial ADP/ATP translocase. Int J Biochem Cell Biol 41, 1371-1380.
7. Sun L, Zhou Z, Xie X, and Bao S#. (2008) Study on biological activity of various truncations of human PRMT5 in E.coli. Progress in Biochemistry and Biophysics 35 (7).
8. Wang, X., Zhang, Y., Ma, Q., Zhang, Z., Xue, Y., Bao, S#., and Chong, K#. (2007). SKB1-mediated symmetric dimethylation of histone H4R3 controls flowering time in Arabidopsis. Embo J 26, 1934-1941.
9. Hou, X., Wang, Y., Zhou, Z., Bao, S., Lin, Y., and Gong, W. (2007). Crystal structure of SAM-dependent O-methyltransferase from pathogenic bacterium Leptospira interrogans. J Struct Biol 159, 523-528.
10. Liu, Z., Zhou, Z., Chen, G., and Bao, S#. (2007). A putative transcriptional elongation factor hIws1 is essential for mammalian cell proliferation. Biochem Biophys Res Commun 353, 47-53.
11. Wang, X., Xu, Y., Han, Y., Bao, S., Du, J., Yuan, M., Xu, Z., and Chong, K. (2006). Overexpression of RAN1 in rice and Arabidopsis alters primordial meristem, mitotic progress, and sensitivity to auxin. Plant Physiol 140, 91-101.
12. Wang, X., Zou, L., Lu, T., Bao, S., Hurov, K. E., Hittelman, W. N., Elledge, S. J., and Li, L. (2006). Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress. Mol Cell 23, 331-341.
13. Cheng, Z., Bao, S., Shan, X., Xu, H., and Gong, W. (2006). Human thioesterase superfamily member 2 (hTHEM2) is co-localized with beta-tubulin onto the microtubule. Biochem Biophys Res Commun 350, 850-853.
14. Bao, S., Lu, T., Wang, X., Zheng, H., Wang, L. E., Wei, Q., Hittelman, W. N., and Li, L. (2004). Disruption of the Rad9/Rad1/Hus1 (9-1-1) complex leads to checkpoint signaling and replication defects. Oncogene 23, 5586-5593.
15. Hu, M. C., Lee, D. F., Xia, W., Golfman, L. S., Ou-Yang, F., Yang, J. Y., Zou, Y., Bao, S., Hanada, N., Saso, H., et al. (2004). IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. Cell 117, 225-237.
16. Bao, S., Qyang, Y., Yang, P., Kim, H., Du, H., Bartholomeusz, G., Henkel, J., Pimental, R., Verde, F., and Marcus, S. (2001). The highly conserved protein methyltransferase, Skb1, is a mediator of hyperosmotic stress response in the fission yeast Schizosaccharomyces pombe. J Biol Chem 276, 14549-14552.
17. Kim, H. W., Yang, P., Qyang, Y., Lai, H., Du, H., Henkel, J. S., Kumar, K., Bao, S., Liu, M., and Marcus, S. (2001). Genetic and molecular characterization of Skb15, a highly conserved inhibitor of the fission yeast PAK, Shk1. Mol Cell 7, 1095-1101.
18. Li, H., Sherman, D. M., Bao, S., and Sherman, L. A. (2001). Pattern of cyanophycin accumulation in nitrogen-fixing and non-nitrogen-fixing cyanobacteria. Arch Microbiol 176, 9-18. |
