課程資訊
課程名稱
 單分子化學生物學方法
METHODS IN SINGLE MOLECULE CHEMICAL BIOLOGY 
開課學期
 97-1 
授課對象
 理學院  化學所化學生物學組  
授課教師
 李弘文 
課號
 Chem5059 
課程識別碼
 223 U2660 
班次
  
學分
 2 
全/半年
 半年 
必/選修
 選修 
上課時間
 星期四3,4(10:20~12:10) 
上課地點
 化121 
備註
 初選不開放。本課程中文授課,使用英文教科書。詳選課須知。外系所學?
限學士班三年級以上 且 限本系所學生(含輔系、雙修生)
總人數上限：20人 
Ceiba 課程網頁
 http://ceiba.ntu.edu.tw/971_sm 
課程簡介影片
 
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課程概述

Section 1: Principles of single-molecule techniques and analysis
- Optical microscopy
- Single molecule fluorescence and single pair FRET
- Optical tweezers, magnetic tweezers methods
- Other novel method development
- Single-molecule data analysis
- Laboratory tour of single-molecule lab

Section 2: Recent significant publications to illustrate how use single molecule methods are used to investigate biochemical mechanisms.

At the end of the second section, students are required to conduct a research project using single molecule methods to address biological mechanisms.
 

課程目標
 This course will present an overview of current experimental state-of-art single molecule techniques used in chemical biology and biophysics. Emphasis will be on two areas: (1) novel single molecule instrumentation and measurement methods, and (2) application of single molecule methods to study the mechanisms of chemical biology processes. 
課程要求
  
預期每週課後學習時數
  
Office Hours
  
指定閱讀
  
參考書目
  
評量方式
(僅供參考)
  
No.
項目
百分比
說明
1. 
 mid-term 
30% 
  
2. 
 class participation 
25% 
  
3. 
 research project 
45% 
  
 
課程進度
週次
日期
單元主題
第01週
 09/18  Single molecule introduction 
第02週
 09/25  DNAzymes (1)
--Ha, T. et al., “Initiation and Re-initiation of DNA Unwinding by the Echerichia Coli Rep Helicase”, Nature 419, 638-641 (2002).
 
第03週
 10/02  DNAzymes (2)
--Dohoney KM, Gelles J.,”Chi-sequence recognition and DNA translocation by single RecBCD helicase/nuclease molecules.” Nature, 409, 370-4 (2001).
--Spies M et al., “RecBCD enzyme switches lead motor subunits in response to chi recognition.” Cell, 131, 694-705 (2007). 
第04週
 10/09  DNAzymes (3)
--Lee JB et al., “DNA primase acts as a molecular brake in DNA replication.” Nature, 439, 621-4 (2006).
 
第05週
 10/16  DNAzymes (4)
--Strick TR et al., “Single-molecule analysis of DNA uncoiling by a type II topoisomerase” Nature, 404, 901-4 (2000).
 
第06週
 10/23  Kinesin (1)
--Hua W et al., “Distinguishing inchworm and hand-over-hand processive kinesin movement by neck rotation measurements.” Science, 295, 844-8 (2002).
 
第07週
 10/30  Kinesin (2)
--Yildiz A et al., “Kinesin walks hand-over-hand.” Science, 303, 676-8 (2004).
 
第08週
 11/06  Myosin (1)
--Forkey JN et al., “Three-dimensional structural dynamics of myosin V by single-molecule fluorescence polarization.” Nature, 422, 399-404 (2003).
 
第09週
 11/13  ~Mid-term Week (research project, no class)~ 
第10週
 11/20  Myosin (2)
--Shiroguchi K, Kinosita K Jr., ”Myosin V walks by lever action and Brownian motion.” Science, 316, 1208-12 (2007).
 
第11週
 11/27  RNA Polymerase
--Abbondanzieri EA et al., “Direct observation of base-pair stepping by RNA polymerase.” Nature, 438, 460-5 (2005).
 
第12週
 12/04  Protein Folding
--Fernandez JM, Li H., “Force-clamp spectroscopy monitors the folding trajectory of a single protein” Science, 303, 1674-8 (2004).
 
第13週
 12/11  Take-home Mid-term 
第14週
 12/18  (research project, no class) 
第15週
 12/25  (research project, no class) 
第16週
 2009/01/01  Holiday 
第17週
 2009/01/08  Research Project Presentation (20 min per group) 
第18週
 2009/01/25  (research project wrap-up, no class)