• project1
    園區核心設施
    NBRP Core Facilities

園區核心設施 - 生醫轉譯研發團隊的後盾 園區核心設施 網頁更新中,服務即將開放申請

基因體研究中心的高速篩選系統(uHTS),是亞洲第一部超高速篩檢設備。此系統使用一條超高速運轉的6-軸機器手臂來執行實驗程序,搭配使用1536孔的微量盤,可以快速完成百萬個微量生化與細胞實驗,協助快速地篩選到具備生物活性的初選化合物(hits)。同時,中央研究院基因體研究中心收集了200萬個以上的化合物,其中包含有最完整的已知成藥、中草藥物、天然物與及其化學衍生物、微生物的代謝分子,還有各式各樣化學合成的小分子等,這些收集非常特殊,其數量與內容在研發界都頗具特色。研究中心的 uHTS 系統精確度高,每次篩選只需使用0.005cc的藥物,節省藥物及試劑,達到經濟的原則。 除了小分子化合物之外,uHTS篩選系統還可以使用在小干擾RNA(siRNA)生物基因靜默(gene silencing)的工作,擴大其廣度與速度。siRNA基因靜默的技術是經由促使特定信使RNA(mRNA)進行降解(broken down),以迅速阻斷相對應標的基因(targeted gene)的表達,以加速尋得和確認具有特定功能的生物分子。此一工作可以發現生物特定功能機制(mechanisms),對生物標的分子(target)與其功能機制做更進一步瞭解,有利於生醫相關的研發等。 不只如此,uHTS篩選系統還可以應用在人類抗體的篩選,加快更多生物細胞表面生物分子的辨示和確認。目前技術已經可以從負責抗體生產的B細胞中,取得抗體基因,輔以基因洗牌技術(gene shuffling)來任意修改決定專一性的抗原結合區(variable domains)的基因,然後植入噬菌體中,以此建立廣大的噬菌體基因庫。運用噬菌體表現 (phage display) 的方法,再經由超高速篩選篩選,找出具高度專一性的噬菌體,取代傳統的細胞融合方法,更快速的得到真正人類單株抗體,成為人體的免疫治療試劑,以維護健康。 中央研究院的超高速篩選系統是一個先進的設施,它可以直接對生物標的物或是對細胞的微量實驗進行自動化、大數量的篩選。所以,無論是以發色(chromophoric)或是細胞型態的變化(phenotypic)為實驗設計,都可以有彈性的在此平台上進行。 預期,由此平台所命中(hits)的產出,可以經由藥化學家與生理學家的努力,以優化(optimize)其結構(structure)效能和藥動與藥效(PK/PD)性能,達到加速生技與製藥的研發能量。

  1.  Charng-Sheng Tsai , Hsin-Yung Yen , Meng-I Lin , Tsung-I Tsai , Shi-Yun Wang , Wen-I Huang , Tsui-Ling Hsu ,Yih-Shyun E Cheng  , Jim-Min Fang , Chi-Huey Wong (2012, Dec).Cell-permeable probe for identification and imaging of sialidases. PNAS, 2013, 110(7), 2466-2471.
  2. Ting-Jen R. Cheng, Shi-Yun Wang, Wen-Hsien Wen, Ching-Yao Su, Mengi Lin, Wen-I Huang, Ming-Tsan Liu, Ho-Sheng Wu, Nung-Sen Wang, Chung-Kai Cheng, Chun-Lin Chen, Chien-Tai Ren, Chung-Yi Wu, Jim-Min Fang, Yih-Shyun E.Cheng, and Chi-Huey Wong (2012, Dec). Chemical Probes for Drug-Resistance Assessment by Binding Competitioin(RABC): Oseltamivir Susceptibility Evaluation. Angew. Chem. Int. Ed., 2013, 52(1), 366-370.
  3. Ting-Jen R. Cheng, Steven Weinheimer, E. Bart Tarbet, Jia-Tsrong Jan, Yih-Shyun E. Cheng, Jiun-Jie Shie, Chun-Lin Chen,  Chih-An Chen,  Wei-Che Hsieh,  Pei-Wei Huang, Wen-Hao Lin, Shi-Yun Wang, Jim-Min Fang, Oliver Yoa-Pu Hu, and Chi-Huey Wong (2012, Sep). Development of Oseltamivir Phosphonate Congeners as Anti-influenza Agents.J. Med. Chem., 2012, 55(20), 8657-8670.
  4. KC Liu; JM Fang; JT Jan; TJR Cheng; SY Wang; ST Yang; YSE Cheng; CH Wong, Enhanced Anti-influenza Agents Conjugated with Anti-inflammatory Activity. Journal of Medicinal Chemistry, 2012, 55(19), 8493-8501.
  5. Huimin Cheng, Junting Wan, Meng-I Lin,‡ Yingxue Liu, Xiaoyun Lu, Jinsong Liu, Yong Xu, Jianxin Chen, Zhengchao Tu, Yih-Shyun E. Cheng, and Ke Ding, (2012, Feb). Design, Synthesis, and in Vitro Biological Evaluation of 1H-1,2,3- Triazole-4-carboxamide Derivatives as New Anti- influenza A Agents Targeting Virus Nucleoprotein. J. Med. Chem., 2012, 55 (5), 2144-2153.
  6. Yu-Fang Shen , Yu-Hou Chen, Shao-Ying Chu, Meng-I Lin, Hua-Ting Hsu, Pei- Yu Wu , Chao-Jung Wu, Hui-Wen Liu, Fu-Yang Lin, Gialih Lin, Pang-Hung Hsu, An-Suei Yang, Yih-Shyun E. Cheng, Ying-Ta Wu, and Chi-Huey Won, Ming-Daw Tsai(2011). E339… R416 salt bridge of nucleoprotein as a feasible target for influenza virus inhibitors. PNAS, 2011, 108 (40), 16515-16520.
  7. Jiun-Jie Shie,† Jim-Min Fang, Po-Ting Lai, Wen-Hsien Wen, Shi-Yun Wang, Yih-Shyun E. Cheng, Keng-Chang Tsai, An-Suei Yang, and Chi-Huey Wong (2011, Sep). A Practical Synthesis of Zanamivir Phosphonate Congeners with Potent Anti-influenza Activity. J. Am. Chem. Soc. , 2011, 133 (44), 17959–17965.
  8. Kung-Cheng Liu, Pei-Shan Lee, Shi-Yun Wang, Yih-Shyun E. Cheng, Jim-Min Fang, Chi-Huey Wong (2011, Jul). Intramolecular ion-pair prodrugs of zanamivir and guanidino-oseltamivir. Bioorganic & Medicinal Chemistry , 2011, 19 (16), 4796–4802.
  9. Kun-Hsien Lin, Jian-Jong Liang, Wen-I Huang, Shao-Ying Lin-Chu, Ching-Yao Su, Yi-Ling Lee, Jia-Tsong Jan, Yi-Ling Lin, Yih-Shyun E. Cheng, and Chi-Huey Wong (2010, Oct). In Vivo Protection Provided by a Synthetic New Alpha-Galactosyl Ceramide Analog against Bacterial and Viral Infections in Murine Models. Antimicroblal Agents and Chemotherapy, 2010, 54 (10) 4129–4136 .
  10. Ting-Jen Rachel Cheng, Ying-Ta Wu, Shih-Ting Yang, Kien-Hock Lo, Shao- Kang Chen, Yin-Hsua Chen, Wen-I Huang, Chih-Hung Yuan, Chih-Wei Guo, Lin-Ya Huang, Kuo-Ting Chen, Hao-Wei Shih, Yih-Shyun E. Cheng, Wei-Chieh Cheng, Chi-Huey Wong  (2010, Oct). High-throughput identification of antibacterials against methicillin-resistant Staphylococcus aureus (MRSA) and the transglycosylase. Bioorganic & Medicinal Chemistry, 2010, 18(24), 8512–8529.
  11. Wen-Hsien Wen, Shi-Yun Wang, Keng-Chang Ysai, Yih-Shyun E. Cheng, An- Suei Yang, Jim-Min Fang, and Chi-Huey Wong. (2010). Analogues of zanamivir with modified C4-substituents as the inhibitors against the group-1 neuraminidases of influenza viruses. Bioorg. Med. Chem., 2010, 18(11), 4074-4084.
  12. Shi-Yun Wang, Ching-Yao Su, Mengi Lin, Shao-Yung Huang, Wen-I Huang, Cheng-Chi Wang, Ying-Ta Wu, Ting- Jen R. Cheng, Hui-Ming Yu, Chien-Tai Ren, Chung-Yi Wu, Chi-Huey Wong, and Yih-Shyun E. Cheng (2009,Feb). HA- Pseudotyped Retroviral Vectors for Influenza Antagonist Screening. Journal of Biomolecular Screening, 2009, 14(3), 294-302.
  13. C. C. Wang, J. R. Chen, Y. C. Tseng, C. H. Hsu, Y. F. Hung, S. W. Chen, C. M. Chen, K. H. Khoo, T. J. R. Cheng, Y-S. E. Cheng (2009). Glycans on influenza hemagglutinin affect receptor binding and immune response. PNAS, 2009, 106(43), 18137-18142.
  14. Wen-Hsien Wen, Mengi Lin, Ching-Yao Su, Shi-Yun Wang, Yih-Shyun E. Cheng, and Jim-Min Fang, Chi-Huey Wong (2009). Synergistic effects of Zanamivir- porphin conjugates on inhibition of neuraminidase and inactivation of influenza viruses. J. Med. Chem, 2009, 52(15), 4903-4910.
  15. Cheng-chen Huang, Chin-Wei Huang1, Yih-Shyun E Cheng and John Yu (2008, Mar). Histamine metabolism influences blood vessel branching in zebrafish reg6 mutants. BMC Developmental Biology, 2008, 8(31) 1-12.
  16. TJR Cheng, MD Sung, HY Liao, YF Chang, CW Chen, CY Huang, LY Chou, YD Wu, YH Chen, YSE Cheng, CH Wong, C Ma, WC Cheng (2008, Jan). Domain Requirement of Moenomycin Binding to Bi-functional Transglycosylases And Its Applica. PNAS , 2008, 105 (2) 431-436.
  17. Ching-Yao Su, Shi-Yun Wang, Jiun-Jie Shie, King-Song Jeng, Nigel J. Temperton, Jim-Min Fang, Chi-Huey Wong, Yih-Shyun E. Cheng (2008). In vitro evaluation of neuraminidase inhibitors using the neuraminidase dependent release assay of hemagglutinin-pseudotyped viruses.. Antiviral Research, 2008, 79(3), 199-205.

● 秘書
   Ms. 伍淑琬
   email: misia@gate.sinica.edu.tw 
   Phone: (02) 2787-1306

● 計畫主持人
   Dr. 馬徹
   email: cma@gate.sinica.edu.tw
   Phone: (02) 2787-1233

● 化合物收集與藥物庫開發 
   Dr. 毛溪山
   email: sshanmao@gate.sinica.edu.tw
   Phone: (02) 2787-1303

   Dr. 楊文彬
   email: wbyang@gate.sinica.edu.tw
   Phone: (02) 2787-1264

● 篩選方法開發 
   Dr. 鄭婷仁
   email: tingjenc@gate.sinica.edu.tw
   Phone: (02) 2787-1267

● 篩選系統操作與化學資訊學 
   Dr. 吳盈達
   email: ywu@gate.sinica.edu.tw
   Phone: (02) 2787-1237