課程簡介
細胞的分子是呈現生命的最小單位。細胞分子生物學就是了解生命的分子在細胞各部位中如何自行排列，如何移動，如何彼此溝通並同步運作。細胞在面對外在世界的變遷時，強韌不拔，有檢查關卡、安全機制、備份計畫和嚴謹的紀錄。沒有任何人造的機制，能像細胞一樣細緻、有組織。不論是人類，動物或者魚貝類，許多生物的運作，都可以從細胞分子生物學的層面來說明，從二十世紀後半葉，生命分子的研究已成為顯學，而且將對我們未來的生活產生更重大的影響。
　　然而，細胞分子生物學卻是植基於實驗而得。許多的現象與理論，都是由於科學家仔細的規畫，設計，實驗，以及觀察而得。了解細胞分子生物學中之經典實驗 (key experiment)，對此學科之深入了解，甚為重要。本學程選擇細胞分子生物學中之重要經典實驗共計21篇，深入討論，研討。

教學目標
本課程為選修，開於研究所博士班，碩士班學生亦可選修。上下學期各三學分，每週上課三小時。其目標為：使研究生了解細胞分子生物學之研究方法，從如何設計實驗，進行實驗，如何解析，以啟發學生之研究興趣，了解研究過程。另外，由於教材全為英文，希望增強學生閱聽英文之能力，精確了解科學英文，以奠定日後閱讀英文期刊，寫作英文論文之能力。

教科書參考書及補充教材
■使用之教科書：
Cooper G.M. and R.E. Hausman (2007). The Cell (4th edition). ASM Press, Washington, D.C.

■其他參考書籍 (學校圖書館有，可參考)：

1. Koolman J. and K.H. Rohm (2005). Color atlas of biochemistry. Thieme Stuttgart. New York.
2. Alberts B., A. Johnson, J. Lewis, M. Raff, K. Roberts and P. Water (2002). Molecular biology of the cell (4th edition). Garland Publishing, Inc. Press.
3. Lodish H., A. Berk, P. Matsudiaira, C.A. Kaiser, M. Krieger, M.P. Scott, S.L. Zipursky, and J. Darnell (2004). Molecular cell biology (4th edition). W.H. Freeman and Company, New York.
4. Karp G. (2002). Cell and molecular biology concepts and experiments (3rd edition). John Wiley & Sons, Inc. Press.
5. Clark D. (2005). Molecular biology. Elsevier Academic Press, MA, USA.
6. Nelson D.L. and M.M. Cox (2005). Lehninger principles of biochemistry (4th edition). W.H. Freeman and Company. New York.

■補充教材：
係由鄭森雄教授參考上述書籍及其他刊物等編寫而得。由學校  製備，上課時發給學生參考。

上課方式

1. 事先閱讀： 每週講解一個經典實驗。學期之初，即將所有教材發給同學。前一週，每一個學生皆需事先全部閱讀教材 (共 A4, 2頁，依學生之程度，約需1-3個晚間，3-10小時)，或複習以前分子生物學之基礎知識。
2. 上課討論：上課時，由教師隨機請一位同學講解，說明一段，原則上所有同學皆會輪到，再由同學發問，解答，最後由教師說明，補充。

評量方式
依據同學說明，講解，討論之表現給分。

課程內容
Introduction
1. Animal cell culture
Nutrition needs of mammalian cells in tissue culture
Harry Eagle
National Institutes of Health, Bethesda, MD
Science, Volumn 122, 1955, pages 501-504.

2. The folding of polypeptide chains
Reductive cleavage of disulfide bridges in ribonuclease
Michael Sela, Frederick H. White, Jr., and Christian B. Anfinsen
National Institutes of Health, Bethesda, MD
Science, Volumn 125, 1957, pages 691-692.

3. The structure of cell membranes
The fluid mosaic model of the structure of cell membranes
S. J. Singer and Garth L. Nicolson
University of California at San Diego and the Salk Institute for
Biological Sciences, La Jolla, CA
Science, Volume 1975, 1972, pages 720-731.

4. The DNA provirus hypothesis
Nature of the provirus of rous sarcoma
Howard M. Temin
McArdle Laboratory, University of Wisconsin, Madison, WI
National Cancer Institute Monographs,
Volume 17, 1964, pages 557-570.

The flow of genetic information

5. The discovery of introns
Spliced segments at the 5’ terminus of adenovirus 2 late mRNA
Susan M. Berget, Claire Moore, and Philip A. Sharp
Massachusetts Institute of Technology, Cambridge, Massachusetts
Proceedings of the National Academy of Sciences USA,
Volume 74, 1977, pages 3171-3175.

6. Isolation of a eukaryotic transcription factor
Affinity purification of sequence-specific DNA-binding proteins
James T. Kadonage and Robert Tjian
University of California, Berkeley
Proceedings of the National Academy of Science,
USA, 1986, Volume 83, pages 5889-5893.

7. The discovery of snRNPs
Antibodies to small unclear RNAs complexed with proteins are
produced by patients with systemic lupus erythematosus
Michael R. Lerner and Joan A. Steitz
Yale University, New Haven, Connecticut
Proceeding of the National Academy of Science, USA,
1979, Volume 76, pages 5495-5499.

8. Catalytic role of ribosomal RNA
Unusual resistance of peptidyl transferase to protein
extraction procedures
Harry F. Noller, Vernita Hoffarth, and Ludwika Zimniak
University of California at Santa Cruz
Science, Volume 256, 1992, pages 1416-1419.

9. Rearrangement of immunoglobulin genes
Evidence for somatic rearrangement of immunoglobulin
genes coding for variable and constant regions
Nobumichi Hozumi and Susumu Tonegawa
Basel Institute for immunology, Basel, Switzerland
Proceedings of the National Academy of Science, USA,
Volume 73, 1976, pages 3628-3632.

10. The human genome
Initial sequencing and analysis of the human genome
International Human Genome Sequencing Consortium
Nature, Volume 409, 2001, pages 860-921
The sequence of the human genome
J. Craig Venter and 273 others
Science, Volume 291, 2001, pages 1304-1351.

Cell structure & function

11. Identification of nuclear localization signals
A short amino acid sequence able to specify nuclear location
Daniel Kalderon, Bruce L. Roberts, William D. Richardson,
and Alan E. Smith
National Institute for Medical Research, Mill Hill, London
Cell, Volume 39, 1984, pages 499-509.

12. The signal hypothesis
Transfer of proteins across membranes. I. presence of proteolytically
Processed and unprocessed nascent immunoglobulin light chains on
Membrane-bound ribosomes of murine myeloma
Gunter Blobel and Bernhard Dobberstein
Rockefeller University, New York
Journal of Cell Biology, 1975, Volume 67, pages 835-851.

13. The LDL receptor
Familial hypercholesterolemia: defective binding of lipoproteins
to cultured fibroblasts associated with impaired regulation of
3-hydroxy-3-methylglutaryl coenzyme A reductase activity
Michael S. Brown and Joseph L. Goldstein
University of Texas Southwestern Medical School, Dallas
Proceedings of the National Academy of Science USA, 1974,
Volume 71, pages 788-792.

14. The isolation of kinesin
Identification of a novel force-generating protein, kinesin,
involved in microtubule-based motility
Ronald D. Vale, Thomas S. Reese, and Michael P. Sheetz
National Institute of Neurological and Communicative Disorders
and Stroke, Marine Biological Lagroatory, Woods Hole, MA;
University of Connecticut Health Center, Farmington, CT;
Stanford University School of Medicine, Stanford, CA
Cell, Volume 42, 1985, pages 39-50.

15. The characterization of integrin
Structure of integrin, a glycoprotein involved in the transmembrane
linkage between fibronectin and actin
John W. Tamkun, Douglas W. DeSimone, Deborah Fonda, Ramila
S. Patel, Clayton Buck, Alan F. Horwitz and Richard O. Hynes
Massachusetts Institute of Technology, Cambridge, Massachusetts
(JWT, DWD, DF, RSP and ROH), The Wistar Institute, Philadelphia,
Pennsylvania (CB) and The University of Pennsylvania School of
Medicine (AFH)
Cell, Volume 46, 1986, pages 271-282.

Cell regulation

16. The Src protein-tyrosine kinase
Transforming gene product of rous sarcoma virus
phosphorylates tyrosine
Tony Hunter and Bartholomew M. Sefton
The Salk Institute, San Diego, CA
Proceedings of the National Academy of Science, USA, 1980,
Volume 77, pages 1311-1315.

17. The discovery of MPF  
Cytoplasmic control of nuclear behavior during meiotic
maturation of frog oocytes
Yoshio Masui and Clement L. Markeert
Yale University, New Haven, CT
Journal of Experimental Zoology, 1971,
Volume 177, pages 129-146.

18. The identification of cyclin
Cyclin: a protein specified by maternal mRNA in sea urchin
eggs that is destroyed at each cleavage division
Tom Evans, Eric T. Rosenthal, Jim Youngblom, Dan Distel,
and Tim Hunt
Marine Biological Laboratory, Woods Hole, MA
Cell, 1983, Volume 33, pages 389-396.

19. Identification of Genes required for programmed cell death
Genetic control of programmed cell death in the nematode C. elegans
Hilary M. Ellis and H. Robert Horvitz
Massachusetts Institute of Technology, Cambridge, MA
Cell, 1986, Volume 44, pages 817-829.

20. Culture of embryonic stem cells
Isolation of a pluripotent cell line from early mouse embryos
cultured in medium conditioned by teratocarcinoma stem cells
Gail R. Martin
University of California, San Francisco, CA
Proceedings of the National Academy of Science, USA, 1981,
Volume 78, pages 7634-7638.

21. The discovery of proto-oncogenes
DNA related to the transforming gene(s) of avian sarcoma viruses is 
present in normal avian DNA
Dominique Stehelin, Harold E. Varmus, J. Michael Bishop
and Peter K. Voge
Department of Microbiology, University of California, San Francisco,
(DS, HEV, and JMB) and Department of Microbiology, University of
California, Los Angeles (PKV) Nature, Volume 260, 1976, pages 170-173.