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  • 柴繼杰

    柴繼杰

    柴繼杰實(shí)驗(yàn)室關(guān)注并研究在生物學(xué)及藥學(xué)應(yīng)用中的重要大分子的結(jié)構(gòu)與功能。主要通過(guò)蛋白晶體衍射的方法及一些生物、生化方面的手段闡述這些生物大分子在結(jié)構(gòu)和功能上的聯(lián)系。我們并不局限于已建立的研究框架,擬與北京生命科學(xué)研究所的其他研究小組合作,在今后的工作中開(kāi)展一些聯(lián)合研究項(xiàng)目。2018年1月8日,柴繼杰的植物油菜素內(nèi)酯等受體激酶的結(jié)構(gòu)及功能研究項(xiàng)目獲得2017年度國(guó)家自然科學(xué)獎(jiǎng)二等獎(jiǎng)。

    教育經(jīng)歷

      清華大學(xué)生命科學(xué)學(xué)院教授 博士生導(dǎo)師

      1987大連輕工業(yè)學(xué)院化學(xué)工程系學(xué)士

      1997中國(guó)協(xié)和醫(yī)科大學(xué)藥物分析學(xué)博士

    工作經(jīng)歷

     。1983-1999)

      1983.09-1987.07 大連輕工業(yè)學(xué)院 學(xué)士

      1987.09-1991.09 丹東鴨綠江造紙廠 助理工程師

      1991.09-1994.07 石油化工科學(xué)研究院 碩士

      1994.09-1997.07 協(xié)和醫(yī)科大學(xué)、藥物研究所 博士

      1997.09-1999.08 中科院生物物理研究所 博士后

      1999.09-2004.07 普林斯頓大學(xué) 博士后

     。2004-2009) 

      2004.07-2009.03 北京生命科學(xué)研究所 研究員

      2009.03-至今 清華大學(xué)生命科學(xué)學(xué)院 教授

    科研方面

    研究概述:

      柴繼杰實(shí)驗(yàn)室關(guān)注并研究在生物學(xué)及藥學(xué)應(yīng)用中的重要大分子的結(jié)構(gòu)與功能。主要通過(guò)蛋白晶體衍射的方法及一些生物、生化方面的手段闡述這些生物大分子在結(jié)構(gòu)和功能上的聯(lián)系。我們并不局限于已建立的研究框架,擬與北京生命科學(xué)研究所的其他研究小組合作,在今后的工作中開(kāi)展一些聯(lián)合研究項(xiàng)目。

    研究方向

      一個(gè)正進(jìn)行的研究方向?qū)㈥P(guān)注專職吞噬細(xì)胞(professional phagocytes)對(duì)調(diào)亡細(xì)胞的識(shí)別途徑。近十年來(lái)大量的工作已對(duì)調(diào)亡調(diào)控的機(jī)制做了詳盡的研究。相對(duì)的,在細(xì)胞調(diào)亡后如何去除調(diào)亡的細(xì)胞殘?bào)w的問(wèn)題并沒(méi)得到關(guān)注。(此問(wèn)題并不是不重要)如果在此環(huán)節(jié)出現(xiàn)問(wèn)題將造成炎癥反應(yīng)的異常持續(xù)和自身免疫的出現(xiàn)。在吞噬細(xì)胞消除調(diào)亡的細(xì)胞體的過(guò)程中,第一步反應(yīng)是調(diào)亡的細(xì)胞體和處于調(diào)亡過(guò)程中的細(xì)胞表面出現(xiàn)如磷脂酰絲氨酸(PS)等可被各種吞噬細(xì)胞上的受體識(shí)別的發(fā)出“eat-me”信號(hào)的信號(hào)分子。近年來(lái)的研究發(fā)現(xiàn)這一識(shí)別過(guò)程并不僅僅是此類信號(hào)分子與吞噬細(xì)胞受體的簡(jiǎn)單結(jié)合。實(shí)際上,一類可被其他吞噬細(xì)胞的受體識(shí)別的橋聯(lián)分子(bridging molecule)如Annexin I(Anx I)也參與了識(shí)別過(guò)程。除此,我們還將對(duì)“donu2019t-eat-me”信號(hào)的識(shí)別機(jī)制及溶血磷脂酰膽堿(LPC)等。

    研究目標(biāo)

      "find-me"信號(hào)的產(chǎn)生和調(diào)控機(jī)制進(jìn)行研究。前者存于正常細(xì)胞,保證這些非調(diào)亡的細(xì)胞不被錯(cuò)誤吞噬;后者為調(diào)亡細(xì)胞所產(chǎn)生,是本實(shí)驗(yàn)室的另一個(gè)研究目標(biāo)是吞噬細(xì)胞識(shí)別和吞噬調(diào)亡細(xì)胞的信號(hào)調(diào)控的分子機(jī)制。前人在線蟲(chóng)(C. elegans)的遺傳學(xué)篩選工作中發(fā)現(xiàn)七個(gè)基因產(chǎn)物分別隸屬于兩條功能上冗余的信號(hào)轉(zhuǎn)導(dǎo)系統(tǒng)參與了清除調(diào)亡細(xì)胞體過(guò)程。其中一條信號(hào)系統(tǒng)為CED-2/ced-5/CED-12/CED10,這條信號(hào)系統(tǒng)保守的存于哺乳類中,其同源信號(hào)系統(tǒng)為CrkII/Dock180/ELMO/RAC,我門(mén)將從蛋白三維結(jié)構(gòu)的尺度研究這條信號(hào)系統(tǒng)的活化和調(diào)控機(jī)制。

    發(fā)表文章

      Zhiwei Huang, Sarah E. Sutton, Adam J. Wallenfang, Robert C. Orchard, Xiaojing Wu, Yingcai Feng, Jijie Chai*, and Neal M. Alto*. Structural insights into GEF mimicry and host GTPase isoform selection by two bacterial type III effector families (*Co-corresponding authors). Nat. Struct. Mol & Biol., 2009 (in press). Jing Dong, Fangming Xiao, Fenxia Fan, Lichuan Gu, Huaixing Cang, Gregory B. Martin* and Jijie Chai*. Crystal structure of the complex between Pseudomonas effector AvrPtoB and the Pto tomato kinase reveals it has both a shared and a unique interface compared with AvrPto-Pto (*Co-corresponding authors), Plant Cell, 2009 (in press).

      Structural basis for activation and inhibition of the secreted chlamydia protease CPAF. Cell Host & Microbe. 2008,4(6), 529-546. Zhiwei Huang, Yingcai Feng, Ding Chen, Xiaojing Wu, Siyang Huang, Xiaojun Wang, Xingguo Xiao, Wenhui Li, Niu Huang, Lichuan Gu, Guangming Zhong and Jijie Chai.

      Maikke B. Ohlson, Zhiwei Huang, Neal M. Alto, Marie-Pierre Blanc, Jack E. Dixon, Chai J.*, and Samuel I. Miller*. Structure and function of SifA indicate that interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tabulation (*Co-corresponding authors). Cell Host & Microbe. 2008, 4(5):434-46.

      Zhou JM, Chai J. Plant pathogenic bacterial type III effectors subdue host responses. Curr Opin Microbiol. 2008 Apr; 11(2):179-85.

      Xiang T, Zong N, Zou Y, Wu Y, Zhang J, Xing W, Li Y, Tang X, Zhu L, Chai J, Zhou JM. Pseudomonas syringae Effector AvrPto Blocks Innate Immunity by Targeting Receptor Kinases. Curr Biol. 2008 Jan 8; 18(1):74-80.

      Chen L, Wang H, Zhang J, Gu L, Huang N, Zhou JM, Chai J. Structural basis for the catalytic mechanism of phosphothreonine lyase. Nat Struct Mol Biol. Nat Struct Mol Biol. 2008 Jan; 15(1):101-2.

      Han Z, Xing X, Hu M, Zhang Y, Liu P, Chai J.Structural basis of EZH2 recognition by EED. Structure. 2007 Oct; 15(10):1306-15.

      Xing W, Zou Y, Liu Q, Liu J, Luo X, Huang Q, Chen S, Zhu L, Bi R, Hao Q, Wu JW, Zhou JM, Chai J. The structural basis for activation of plant immunity by bacterial effector protein AvrPto. Nature. 2007 Sep 13; 449(7159):243-7.

      Zhang J, Shao F, Li Y, Cui H, Chen L, Li H, Zou Y, Long C, Lan L, Chai J, Chen S, Tang X, Zhou JM. Cell Host & Microbe. 2007 May 17, 1(3):175-85.

      Wang H, Yan Y, Liu L, Huang H, Shen Y, Chen L, Chen Y, Yang Q, Hao Q, Wang K, Chai J, Structural Basis for Modulation of Kv4 K+ Channels by Auxiliary KChIP Subunits. Nature Neuroscience, 2007 Jan; 10(1):32-9.

      Zhang T, Sun Y, Tian E, Deng H, Zhang Y, Luo X, Cai Q, Wang H, Chai J, Zhang H. RNA-binding proteins SOP-2 and SOR-1 form a novel PcG-like complex in C. elegans. Development. 2006 Mar; 133(6):1023-33.

      Han Z, Guo L, Wang H, Shen Y, Deng XW, Chai J. Structural basis for the specific recognition of methylated histone H3 lysine 4 by the WD-40 protein WDR5. Mol. Cell 2006, 22(1):137-44.

      Yan N, Wu JW, Chai J, Li W, Shi Y. Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid and Grim. “Nat Struct Mol Biol. 2004 May;11(5):420-8. Epub 2004 Apr 25.”

      Yan N, Chai J, Lee ES, Gu L, Liu Q, He J, Wu J-W, Kokel D, Li H, Hao Q, Xue .D, and Shi Y. Structure of the CED-4/CED-9 complex reveals insights into programmed cell death in Caenorhabditis elegans. Nature, 2005 Oct 6; 437(7060):831-7.

      Chai J*, Yan N*, Huh JR, Wu JW, Li W, Hay BA, Shi Y. “Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination.” Nat Struct Biol. 2003 Nov; 10(11):892-8. (* These authors contributed equally to the work ).

      Yan N, Gu L, Kokel D, Chai J, Li W, Han A, Chen L, Xue D, Shi Y. Structural, biochemical, and functional analyses of CED-9 recognition by the proapoptotic proteins EGL-1 and CED-4. Mol Cell. 2004 15(6):999-1006.

      Yan N, Wu JW, Chai J, Li W, Shi Y. Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid and Grim. Nat Struct Mol Biol. 2004, 11(5):420-8.

      Chai J, Wu JW, Yan N, Massagué J, Pavletich NP, Shi Y. Features of a Smad3 MH1-DNA complex. Roles of water and zinc in DNA binding. J Biol Chem. 2003, 278(22):20327-3.

      Shiozaki EN, Chai J, Rigotti DJ, Riedl SJ, Li P, Srinivasula SM, Alnemri ES, Fairman R, Shi Y. Mechanism of XIAP-mediated inhibition of caspase-9. Mol Cell. 2003, 11(2):519.

      Wang X, Yang C, Chai J, Shi Y, Xue D. Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans. Science. 2002 Nov 22; 298(5598):1587-92.

      Wu JW, Krawitz AR, Chai J, Li W, Zhang F, Luo K, Shi Y. Structural mechanism of Smad4 recognition by the nuclear oncoprotein Ski: insights on Ski-mediated repression of TGF-beta signaling. Cell. 2002, 111(3):357-67.

      Li W, Srinivasula SM, Chai J, Li P, Wu JW, Zhang Z, Alnemri ES, Shi Y. Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi. Nat Struct Biol. 2002, 9(6):436.

      Shiozaki EN, Chai J, Shi Y. Oligomerization and activation of caspase-9, induced by Apaf-1 CARD. Proc Natl Acad Sci U S A. 2002, 99(7):4197-202.

      Wu JW, Hu M, Chai J, Seoane J, Huse M, Li C, Rigotti DJ, Kyin S, Muir TW, Fairman R, Massagué J, Shi Y. Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling. Mol Cell. 2001, 8(6):1277

      Chai J, Wu Q, Shiozaki E, Srinivasula SM, Alnemri ES, Shi Y. “Crystal structure of a procaspase-7 zymogen: mechanisms of activation and substrate binding,” Cell 2001 Nov 2;107(3):399-407.

      Wu JW, Cocina AE, Chai J, Hay BA, Shi Y. Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides. Mol Cell. 2001, 8(1):95

      Srinivasula SM, Hegde R, Saleh A, Datta P, Shiozaki E, Chai J, Lee RA, Robbins PD, Fernandes-Alnemri T, Shi Y, Alnemri ES. A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature. 2001 Mar 1; 410(6824):112-6.

      Chai J, Shiozaki E, Srinivasula SM, Wu Q, Datta P, Alnemri ES, Shi Y. Structural basis of caspase-7 inhibition by XIAP. Cell. 2001 Mar 9; 104(5):769-80.

      Wu G*, Chai J*, Suber TL, Wu JW, Du C, Wang X, Shi Y. “Structural basis of IAP recognition by Smac/DIABLO,” Nature 2000 Dec 21-28; 408 (*These authors contributed equally to the work ).

      Chai J , Du C, Wu JW, Kyin S, Wang X, Shi Y. Structural and biochemical basis of apoptotic activation by Smac/DIABLO. Nature. 2000 Aug 24; 406(6798):855-62.

    榮譽(yù)記錄

    2018年1月8日,柴繼杰的植物油菜素內(nèi)酯等受體激酶的結(jié)構(gòu)及功能研究項(xiàng)目獲得2017年度國(guó)家自然科學(xué)獎(jiǎng)二等獎(jiǎng)。

    TAGS: 人物 博士 博士后 學(xué)者 PI
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