研究方向

我們的研究團隊，希望結合化學領域和生物物理的知識，來探索生物系統中複雜的化學反應，以及其調控的機制。更期望能開發出新的技術，解決有關神經退化性疾病的問題。

1. 開發新式的螢光試劑及標定的技術，在複雜的生物系統中標定蛋白質的特定位置，並找出錯誤折疊的蛋白和神經退化性疾病的關連性。現階段主要的鎖定的是漸凍人(ALS)疾病的研究，期望找出其相關蛋白TDP-43的特性，以及了解TDP-43和漸凍人疾病的關連，開發並合成可能的藥物。

2. 應用生物物理及有機化學的方法，加上螢光光譜及螢光共振能量轉移光譜(FRET)，結合無細胞系統(Cell free system)，及含有螢光團的tRNA突變株，來模擬細胞內新生蛋白的結構。並探討轉譯過程中，新生蛋白與伴隨蛋白(Chaperone)的作用，以及不正常折疊蛋白和伴隨蛋白的作用機制。

3. 利用螢光光譜、圓二色光譜儀、核磁共振光譜儀、質譜儀等技術，研究有關蛋白質折疊的作用機制及動力學。

 

 

In an effort to clarify the physical properties of the C-terminal domain of TDP-43, we have synthesized peptide fragments and shown that only D1 within D1-4 can form twisted fibrils.
(A) PONDR analysis of the full-length TDP-43 (1-414).Calculations use VL3 version of PONDR. EM images of (B) D1, (C) 315T, and (D) G294A incubated in pH 7.0 phosphate buffer at 37℃ for 2 weeks. The scale bars represent 100 nm.

 

研究著作

• Koubek, J., Lin, K.-F., Chen, Y.-R., Cheng, R.-P., Huang, J. J.-T.* Strong anion exchange fast performance liquid chromatography as a versatile tool for preparation and purification of RNA produced by in vitro transcription. RNA, 2013 (in press)
• Huang, Y.-C. Lin, K.-F, He, R.-Y., Tu, P.-H. Koubek, J., Hsu,Y.-C., Huang, J. J.-T.* Inhibition of TDP-43 aggregation by nucleic acid binding. PLoS One 2013, 8(5), e64002

• Chang, C.-K., Wu, T.-H., Wu, C.-Y., Chiang, M.-H., Toh, E.-K., Hsu, Y.-C., Lin, K.-F., Liao, Y.-H., Huang, T.-H.*, Huang, J. J.-T.* The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity. Biochem. Biophys. Res. Commun. 2012, 425, 219-224

• Lin, K.-F., Sun, C.-S., Huang, Y.-C., Chan, S.-I., Koubek, J., Wu, T.-H., Huang, J. J.-T.* Cotranslational Protein Folding within the Ribosome Tunnel Influences Trigger-Factor Recruitment. Biophys. J. 2012, 102, 2818-2827.
• Lin, K.-F., Sun, C.-S., Huang, Y.-C., Chan, S.-I., Koubek, J., Wu, T.-H., Huang, J. J.-T.* Cotranslational Protein Folding within the Ribosome Tunnel Influences Trigger-Factor Recruitment. Biophys. J. 2012, 102, 2818-2827.
• Huang, J. J.-T.; Larsen, R.-W.; Chan, S.-I.* The Interplay of Turn Formation and Hydrophobic Interactions on the Early Kinetic Events in Protein Folding. Chem. Comm. 2012, (Feature Article), 48, 487-497.
• Chen, K.-H., Lin, Y.-Y., Xie, Z.-J., Tu, P.-H., Chen, P.-Y., Liao, T.-Y.,Huang, J. J.-T.* Induction of Amyloid Fibrils by the C-terminal Fragment of TDP-43 in Amyotrophic Lateral Sclerosis. J. Am. Chem. Soc.2010, 132, 1186.