研究領域與專長

我們致力於細菌細胞分裂機制的研究,以生長分裂過程的細胞骨架功能和細胞膜-蛋白質交互作用為研究重點。說明如下:

  1. 小細胞系統振盪現像與膜蛋白定位

    大腸桿菌利用小細胞系統對細胞分裂位點進行精準的空間調控。小細胞系統由三個蛋白質組成,附著於細胞膜表層,在桿狀細胞的兩個端點間來回振盪,用以建立促使自細胞中點進行分裂的濃度梯度。小細胞系統蛋白MinD及MinE具有在細胞膜上進行自組裝的能力,當有充足腺苷三磷酸供應時,會在細胞膜上持續進行規律的泳動,形成中尺度圖樣。過去我們對小細胞系統蛋白的自組裝能力及與細胞膜的交互作用進行生化特性探討,並結合顯微影像技術及體外重建的仿生膜系統,用以了解小細胞系統蛋白與細胞膜交互作用於時間與空間上的變化。
    除已知的分裂隔板定位功能外,近期我們發現小細胞系統於細胞膜上的振盪現像,能影響數種蛋白質於細胞膜上的定位,進而假設小細胞系統能調節附著性膜蛋白於細胞質與細胞膜之間的存在平衡態,藉此調節蛋白質功能。目前我們正針對此假說進行驗證。

  2. 細胞膜的物化性質與分裂蛋白的分佈動態關係

    以仿生膜系統研究蛋白質與細胞膜交互作用,可釐清生化條件與隨時間及空間變化的交互作用關係。因此我們透過合作,發展可用於分離及檢測膜蛋白的仿生膜平台,預期對不同形狀、表面電性、及掛膜方式的膜蛋白進行分佈動態的定性及定量分析。

  3. 細菌生理與抗藥機制

    研究細菌生理是了解病原細菌產生抗藥性及尋找新型抗生素的基礎。於上述研究中我們發現細菌內膜的平衡態會影響細菌對抗生素的敏感度以及代謝功能。因此希望透過對細菌外套及關鍵代謝酵素的研究,尋找克服細菌抗藥性的方法。

學經歷
經歷
  • 2014 – 迄今   副研究員, 中研院生化所
  • 2006 – 2014   助研究員, 中研院生化所
  • 2004 – 2006   講師, 美國康乃迪克大學健康中心分子生物微生物及結構生物學系
  • 1999 – 2003   博士後研究, 美國康乃迪克大學健康中心分子生物微生物及結構生物學系
學歷
  • 1996 – 1999   博士, 生物化學系, 英國劍橋大學
  • 1992 – 1994   碩士, 植物病蟲害學系, 國立臺灣大學
  • 1988 – 1992   學士, 植物病蟲害學系, 國立臺灣大學
主要著作
Shih YL*, Huang LT, Tu YM, Lee BF, Bau YC, Hong CY, Lee HL, Shih YP, Hsu MF, Lu ZX, Chen JS, Chao L*
Biophysical Journal (2019)
Lee HL, Chiang IC, Liang SY, Lee DY, Chang GD, KY Wang, Lin SY, Shih YL
MOLECULAR & CELLULAR PROTEOMICS (2016)
Zheng M, Chiang YL, Lee HL, Kong LR, Hsu ST, Hwang IS, Rothfield LI and Shih YL
J Biol Chem (2014)
Shih YL, Huang KF, Lai HM, Liao JH, Lee CS, Chang CM, Mak HM, Hsieh CW & Lin CC
PLoS One (2011)
Hsieh CW, Lai HM, Lin CC, Lin TY, Hsieh TS, Shih YL
Molecular Microbiology (2010)
Shih YL*, Kawagishi I and Rothfield LI*
Mol Microbiol (2005)
Shih YL, Le T, Rothfield LI*
Proc Natl Acad Sci USA (2003)
Shih YL, Fu X, King GF, Le T and Rothfield LI*
EMBO J (2002)
著作列表
  1. Wu CF, Lien YW, Bondage D, Lin JS, Pilhofer M, (Shih YL), Chang JH, Lai EM*  (2020-01)  EMBO Reports  21(1), e47961  "Effector loading onto the VgrG carrier activates type VI secretion system assembly."
  2. (Shih YL)*, Huang LT, Tu YM, Lee BF, Bau YC, Hong CY, Lee HL, Shih YP, Hsu MF, Lu ZX, Chen JS, Chao L*  (2019-04)  BIOPHYSICAL JOURNAL  116(8), 1469-1482  "Active Transport of Membrane Components by Self-Organization of the Min Proteins."
  3. Chen WJ, Kuo TY, Hsieh FC, Chen PY, Wang CS, (Shih YL), Lai YM, Liu JR, Yang YL, and Shih MC*  (2016-09)  Scientific Reports  6, 32950  "Involvement of type VI secretion system in secretion of iron chelator pyoverdine in Pseudomonas taiwanensis"
  4. Liang SY, Lin SY, Chiang IC, (Shih YL*)  (2016-05)  Data in Brief  8, 304-307  "Quantitative inner membrane proteome datasets of the wild-type and the Δmin mutant of Escherichia coli"
  5. Liao JH, Chien CT, Wu, HY, Huang KF, Wang I, Ho MR, Tu IF, Lee IM, Li W, (Shih YL), Wu CY, Lukyanov P, Hsu STD, Wu SH*  (2016-04)  J Am Chem Soc  138(14), 4787-4795  "A multivalent marine lectin from Crenomytilus grayanus possesses anti-cancer activity through recognizing globotriose Gb3"
  6. Lee HL, Chiang IC, Liang SY, Lee DY, Chang GD, KY Wang, Lin SY, (Shih YL*)  (2016-02)  MOLECULAR & CELLULAR PROTEOMICS  15, 1572-1583  "Quantitative proteomics analysis reveals the Min system of Escherichia coli modulates reversible protein association with the inner membrane"
  7. Chiang YL, Chang YC, Chiang IC, Mak HM, Hwang IS*, (Shih YL)*  (2015-11)  PloS one  10(11), e0142506  "Atomic Force Microscopy Characterization of Protein Fibrils Formed by the Amyloidogenic Region of the Bacterial Protein MinE on Mica and a Supported Lipid Bilayer."
  8. Rujiviphat J, Wong MK, Won A, (Shih YL), Yip CM and McQuibban AG*  (2015-03)  J Mol Biol  427(16), 2595-2598  "Mitochondrial Genome Maintenance 1 (Mgm1) Protein alters membrane topology and promotes local membrane bending"
  9. Zheng M, Chiang YL, Lee HL, Kong LR, Hsu ST, Hwang IS, Rothfield LI, (Shih YL)*   (2014-08)  J Biol Chem  289(31), 21252-21266  "Self-Assembly of MinE on the Membrane Underlies Formation of the MinE-Ring to Sustain Function of the E. coli Min System"
  10. (Shih YL)*, Zheng M  (2013-12)  Environmental Microbiology  15(12), 3229-3239  "Spatial control of the cell division site by the Min system in E. coli"
  11. (Shih YL)*, Huang KF, Lai HM, Liao JH, Lee CS, Chang CM, Mak HM, Hsieh CW & Lin CC  (2011)  PLoS One  6(6), e21425  "The N-terminal amphipathic helix of the topological specificity factor MinE is associated with shaping membrane curvature"
  12. Hsieh CW, Lai HM, Lin CC, Lin TY, Hsieh TS, (Shih YL)*  (2010)  MOLECULAR MICROBIOLOGY  75(2), 499-512  "Direct MinE-membrane interaction contributes to the proper localization of MinDE in E. coli"
  13. Vats P, Shih YL, Rothfield L  (2009)  Molecular microbiology  72(1), 170-182  "Assembly of the MreB-associated cytoskeletal ring of Escherichia coli."
  14. Pradel N, Santini CL, Bernadac A, Shih YL, Goldberg MB, Wu LF  (2007)  Biochemical and biophysical research communications  353(2), 493-500  "Polar positional information in Escherichia coli spherical cells."
  15. Y-L Shih, LI Rothfield  (2006)  Microbiology and Molecular Biology Reviews  70, 729-754  "The bacterial cytoskeleton"
  16. LI Rothfield, A Taghbalout and Y-L Shih  (2005)  Nat Rev Microbiol  3, 959-968  "Spatial control of bacterial division-site placement"
  17. Y-L Shih, I Kawagishi and LI Rothfield  (2005)  Mol Microbiol  58, 917-928  "The MreB and Min cytoskeletal-like systems play independent roles in prokaryotic polar differentiation"
  18. Shih YL, Le T, Rothfield L  (2003)  Proceedings of the National Academy of Sciences of the United States of America  100(13), 7865-7870  "Division site selection in Escherichia coli involves dynamic redistribution of Min proteins within coiled structures that extend between the two cell poles."
  19. Y-L Shih, X Fu, GF King , T Le and LI Rothfield  (2002)  EMBO J  21, 3347-3357  "Division site placement in E.coli: mutations that prevent formation of the MinE ring lead to loss of the normal midcell arrest of growth of polar MinD membrane domains"
  20. Rothfield LI, Shih YL, King G  (2001)  Cell  106(1), 13-16  "Polar explorers: membrane proteins that determine division site placement."
  21. Fu X, Shih YL, Zhang Y, Rothfield LI  (2001)  Proceedings of the National Academy of Sciences of the United States of America  98(3), 980-985  "The MinE ring required for proper placement of the division site is a mobile structure that changes its cellular location during the Escherichia coli division cycle."
  22. King GF, Shih YL, Maciejewski MW, Bains NP, Pan B, Rowland SL, Mullen GP, Rothfield LI  (2000)  Nature Structural Biology  7(11), 1013-1017  "Structural basis for the topological specificity function of MinE."
  23. Shih YL, Harris SJ, Borner G, Rivet MM, Salmond GP  (1999)  Environmental microbiology  1(6), 535-547  "The hexY genes of Erwinia carotovora ssp. carotovora and ssp. atroseptica encode novel proteins that regulate virulence and motility co-ordinately."
  24. Harris SJ, Shih YL, Bentley SD, Salmond GP  (1998)  Molecular microbiology  28(4), 705-717  "The hexA gene of Erwinia carotovora encodes a LysR homologue and regulates motility and the expression of multiple virulence determinants."
  25. Toth I, Mulholland V, Copper V, Bentley S, Shih Y-L, Perombelon M, and Salmond GPC  (1997)  Microbiology  143, 2433-2438  "Generalized transduction in the potato blackleg pathogen Erwinia carotovora subsp. atroseptica by bacteriophage φM1"

我們致力於細菌細胞分裂機制的研究,以生長分裂過程的細胞骨架功能和細胞膜-蛋白質交互作用為研究重點。說明如下:

  1. 小細胞系統振盪現像與膜蛋白定位

    大腸桿菌利用小細胞系統對細胞分裂位點進行精準的空間調控。小細胞系統由三個蛋白質組成,附著於細胞膜表層,在桿狀細胞的兩個端點間來回振盪,用以建立促使自細胞中點進行分裂的濃度梯度。小細胞系統蛋白MinD及MinE具有在細胞膜上進行自組裝的能力,當有充足腺苷三磷酸供應時,會在細胞膜上持續進行規律的泳動,形成中尺度圖樣。過去我們對小細胞系統蛋白的自組裝能力及與細胞膜的交互作用進行生化特性探討,並結合顯微影像技術及體外重建的仿生膜系統,用以了解小細胞系統蛋白與細胞膜交互作用於時間與空間上的變化。
    除已知的分裂隔板定位功能外,近期我們發現小細胞系統於細胞膜上的振盪現像,能影響數種蛋白質於細胞膜上的定位,進而假設小細胞系統能調節附著性膜蛋白於細胞質與細胞膜之間的存在平衡態,藉此調節蛋白質功能。目前我們正針對此假說進行驗證。

  2. 細胞膜的物化性質與分裂蛋白的分佈動態關係

    以仿生膜系統研究蛋白質與細胞膜交互作用,可釐清生化條件與隨時間及空間變化的交互作用關係。因此我們透過合作,發展可用於分離及檢測膜蛋白的仿生膜平台,預期對不同形狀、表面電性、及掛膜方式的膜蛋白進行分佈動態的定性及定量分析。

  3. 細菌生理與抗藥機制

    研究細菌生理是了解病原細菌產生抗藥性及尋找新型抗生素的基礎。於上述研究中我們發現細菌內膜的平衡態會影響細菌對抗生素的敏感度以及代謝功能。因此希望透過對細菌外套及關鍵代謝酵素的研究,尋找克服細菌抗藥性的方法。

經歷
  • 2014 – 迄今   副研究員, 中研院生化所
  • 2006 – 2014   助研究員, 中研院生化所
  • 2004 – 2006   講師, 美國康乃迪克大學健康中心分子生物微生物及結構生物學系
  • 1999 – 2003   博士後研究, 美國康乃迪克大學健康中心分子生物微生物及結構生物學系
學歷
  • 1996 – 1999   博士, 生物化學系, 英國劍橋大學
  • 1992 – 1994   碩士, 植物病蟲害學系, 國立臺灣大學
  • 1988 – 1992   學士, 植物病蟲害學系, 國立臺灣大學
Shih YL*, Huang LT, Tu YM, Lee BF, Bau YC, Hong CY, Lee HL, Shih YP, Hsu MF, Lu ZX, Chen JS, Chao L*
Biophysical Journal (2019)
Lee HL, Chiang IC, Liang SY, Lee DY, Chang GD, KY Wang, Lin SY, Shih YL
MOLECULAR & CELLULAR PROTEOMICS (2016)
Zheng M, Chiang YL, Lee HL, Kong LR, Hsu ST, Hwang IS, Rothfield LI and Shih YL
J Biol Chem (2014)
Shih YL, Huang KF, Lai HM, Liao JH, Lee CS, Chang CM, Mak HM, Hsieh CW & Lin CC
PLoS One (2011)
Hsieh CW, Lai HM, Lin CC, Lin TY, Hsieh TS, Shih YL
Molecular Microbiology (2010)
Shih YL*, Kawagishi I and Rothfield LI*
Mol Microbiol (2005)
Shih YL, Le T, Rothfield LI*
Proc Natl Acad Sci USA (2003)
Shih YL, Fu X, King GF, Le T and Rothfield LI*
EMBO J (2002)
  1. Wu CF, Lien YW, Bondage D, Lin JS, Pilhofer M, (Shih YL), Chang JH, Lai EM*  (2020-01)  EMBO Reports  21(1), e47961  "Effector loading onto the VgrG carrier activates type VI secretion system assembly."
  2. (Shih YL)*, Huang LT, Tu YM, Lee BF, Bau YC, Hong CY, Lee HL, Shih YP, Hsu MF, Lu ZX, Chen JS, Chao L*  (2019-04)  BIOPHYSICAL JOURNAL  116(8), 1469-1482  "Active Transport of Membrane Components by Self-Organization of the Min Proteins."
  3. Chen WJ, Kuo TY, Hsieh FC, Chen PY, Wang CS, (Shih YL), Lai YM, Liu JR, Yang YL, and Shih MC*  (2016-09)  Scientific Reports  6, 32950  "Involvement of type VI secretion system in secretion of iron chelator pyoverdine in Pseudomonas taiwanensis"
  4. Liang SY, Lin SY, Chiang IC, (Shih YL*)  (2016-05)  Data in Brief  8, 304-307  "Quantitative inner membrane proteome datasets of the wild-type and the Δmin mutant of Escherichia coli"
  5. Liao JH, Chien CT, Wu, HY, Huang KF, Wang I, Ho MR, Tu IF, Lee IM, Li W, (Shih YL), Wu CY, Lukyanov P, Hsu STD, Wu SH*  (2016-04)  J Am Chem Soc  138(14), 4787-4795  "A multivalent marine lectin from Crenomytilus grayanus possesses anti-cancer activity through recognizing globotriose Gb3"
  6. Lee HL, Chiang IC, Liang SY, Lee DY, Chang GD, KY Wang, Lin SY, (Shih YL*)  (2016-02)  MOLECULAR & CELLULAR PROTEOMICS  15, 1572-1583  "Quantitative proteomics analysis reveals the Min system of Escherichia coli modulates reversible protein association with the inner membrane"
  7. Chiang YL, Chang YC, Chiang IC, Mak HM, Hwang IS*, (Shih YL)*  (2015-11)  PloS one  10(11), e0142506  "Atomic Force Microscopy Characterization of Protein Fibrils Formed by the Amyloidogenic Region of the Bacterial Protein MinE on Mica and a Supported Lipid Bilayer."
  8. Rujiviphat J, Wong MK, Won A, (Shih YL), Yip CM and McQuibban AG*  (2015-03)  J Mol Biol  427(16), 2595-2598  "Mitochondrial Genome Maintenance 1 (Mgm1) Protein alters membrane topology and promotes local membrane bending"
  9. Zheng M, Chiang YL, Lee HL, Kong LR, Hsu ST, Hwang IS, Rothfield LI, (Shih YL)*   (2014-08)  J Biol Chem  289(31), 21252-21266  "Self-Assembly of MinE on the Membrane Underlies Formation of the MinE-Ring to Sustain Function of the E. coli Min System"
  10. (Shih YL)*, Zheng M  (2013-12)  Environmental Microbiology  15(12), 3229-3239  "Spatial control of the cell division site by the Min system in E. coli"
  11. (Shih YL)*, Huang KF, Lai HM, Liao JH, Lee CS, Chang CM, Mak HM, Hsieh CW & Lin CC  (2011)  PLoS One  6(6), e21425  "The N-terminal amphipathic helix of the topological specificity factor MinE is associated with shaping membrane curvature"
  12. Hsieh CW, Lai HM, Lin CC, Lin TY, Hsieh TS, (Shih YL)*  (2010)  MOLECULAR MICROBIOLOGY  75(2), 499-512  "Direct MinE-membrane interaction contributes to the proper localization of MinDE in E. coli"
  13. Vats P, Shih YL, Rothfield L  (2009)  Molecular microbiology  72(1), 170-182  "Assembly of the MreB-associated cytoskeletal ring of Escherichia coli."
  14. Pradel N, Santini CL, Bernadac A, Shih YL, Goldberg MB, Wu LF  (2007)  Biochemical and biophysical research communications  353(2), 493-500  "Polar positional information in Escherichia coli spherical cells."
  15. Y-L Shih, LI Rothfield  (2006)  Microbiology and Molecular Biology Reviews  70, 729-754  "The bacterial cytoskeleton"
  16. LI Rothfield, A Taghbalout and Y-L Shih  (2005)  Nat Rev Microbiol  3, 959-968  "Spatial control of bacterial division-site placement"
  17. Y-L Shih, I Kawagishi and LI Rothfield  (2005)  Mol Microbiol  58, 917-928  "The MreB and Min cytoskeletal-like systems play independent roles in prokaryotic polar differentiation"
  18. Shih YL, Le T, Rothfield L  (2003)  Proceedings of the National Academy of Sciences of the United States of America  100(13), 7865-7870  "Division site selection in Escherichia coli involves dynamic redistribution of Min proteins within coiled structures that extend between the two cell poles."
  19. Y-L Shih, X Fu, GF King , T Le and LI Rothfield  (2002)  EMBO J  21, 3347-3357  "Division site placement in E.coli: mutations that prevent formation of the MinE ring lead to loss of the normal midcell arrest of growth of polar MinD membrane domains"
  20. Rothfield LI, Shih YL, King G  (2001)  Cell  106(1), 13-16  "Polar explorers: membrane proteins that determine division site placement."
  21. Fu X, Shih YL, Zhang Y, Rothfield LI  (2001)  Proceedings of the National Academy of Sciences of the United States of America  98(3), 980-985  "The MinE ring required for proper placement of the division site is a mobile structure that changes its cellular location during the Escherichia coli division cycle."
  22. King GF, Shih YL, Maciejewski MW, Bains NP, Pan B, Rowland SL, Mullen GP, Rothfield LI  (2000)  Nature Structural Biology  7(11), 1013-1017  "Structural basis for the topological specificity function of MinE."
  23. Shih YL, Harris SJ, Borner G, Rivet MM, Salmond GP  (1999)  Environmental microbiology  1(6), 535-547  "The hexY genes of Erwinia carotovora ssp. carotovora and ssp. atroseptica encode novel proteins that regulate virulence and motility co-ordinately."
  24. Harris SJ, Shih YL, Bentley SD, Salmond GP  (1998)  Molecular microbiology  28(4), 705-717  "The hexA gene of Erwinia carotovora encodes a LysR homologue and regulates motility and the expression of multiple virulence determinants."
  25. Toth I, Mulholland V, Copper V, Bentley S, Shih Y-L, Perombelon M, and Salmond GPC  (1997)  Microbiology  143, 2433-2438  "Generalized transduction in the potato blackleg pathogen Erwinia carotovora subsp. atroseptica by bacteriophage φM1"