Outline

Introduction by Yi Rao, September, 2004

生命科学的概念和技术

第一堂课的目的:

首要是 转变观念:
你的中心任务: 不再是“读书”而是“发现”
次要是 给后来课稍铺垫
介绍一些常用技术:发明过程,应用决心

生命科学思想

生命科学的思想和概念容易学习和理解,导致一种错觉:以为生命科学的研究很容易,
甚至以为只要有经费和出力气就行
生命科学的思想和概念难在于
首先提出,
或者证明 (最常见的困难)
或者接受
不同例子来说明
通过讲你们大学已经学过的一段分子遗传学,从研究进展的角度重新讲,看
研究和读书的差别: 促使大家开始用研究的眼光看问题庭
讲你们没有学过的,看现在怎么决定进一步?

从人类认识来说
1)已经清楚的: 从种瓜得瓜到遗传密码

Avery, MacCleod,and McCarty (1944) 转化实验:背景,结果,解释,争议/

不接受的理由,谁先接受
Watson and Crick 对 Franklin: 思考理论模型 对 结果资料自然明了
想象力和创造性: 碱基配对
遗传密码: 理论和实验的相互依存,相互促进
遗传密码概念的提出: Gamow 简单,且可以实验资料检验的理论
数字巧合:不能不重要,还是纯粹碰巧?
Astbury: 碱基间距离 and 氨基酸间距
Watson and Crick: 碱基对间氢键距离符合双螺旋结构空间限制
Gamow: 20 cavities, 20 aa

tRNA 的提出: 敏锐理论思维的作用

without the adaptor hypothesis, experimentalists did not know why they
were getting RNA attached to amino acids
遗传密码的破译: 实验资料最后解决问题
 Without direct experimentation, it was not possible to solve the coding
problem or predict the exact codes

2)半懂不懂的: 从慢病毒到蛋白质催化的构相转变
Prion 发病原理: Protein-only, or with nucleic acids
蛋白质如何复制自己,或将自己传染给其它蛋白质分子?
Transmissible spongiform encephalopathies (TSEs)
或 Prion 病
蛋白质假说的提出
Prion 的分离
蛋白质假说: 支持和不支持的理由
先发 Nobel 奖,后证明?
蛋白质假说: 何去和从?
漂亮 or 简单的理论 对 不漂亮 or 复杂的资料:Crick 的说法,Watson 的应用,到
prion,你又怎么看?

3)还没入门的: 对脸的识别

生命科学技术
为了解决重要问题,而发明或应用关键技术
有些技术是怎么发明的?
敢于应用以前不熟悉,或复杂,但是必需的技术

细胞和分子水平
Cell based: fate mapping, transplantation, nuclear transfer

DNA: genetics, manipulations of genes

Mario Cappechi and 基因剔除
RNA: hybridization, RNAi
Andrew Fire, Guo (郭苏) and Kempheus 和 RNAi
Protein: antibodies, GFP
Douglas Prasher and GFP
Chemistry: purification, synthesis
Rabbit pheromone and gas chromatography
Physics: structural biology, modern imaging
From Bernal to MacKinnon

生命科学技术应用
用最新或者优美的技术发现或者解决问题
用旧或者不怎么优美的技术发现或者解决问题

用你熟悉的技术发现或者解决问题
学习和使用你不熟悉的技术发现或者解决问题
必读文献

Nirenberg, M. W., and Matthaei, J. H. (1961). The dependence of cell-free protein

synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides. Proc.
Natl. Acad. Sci. U. S. A. 47: 1588–1602.

Legname G, Baskakov IV, Nguyen HO, Riesner D, Cohen FE, DeArmond SJ, Prusiner
SB.(2004). Synthetic mammalian prions. Science 305:673-6.

选读文献

1) 综述/书
Sturtevant, A.H. (1965). A History of Genetics. Harper & Row, New York.
Watson, J. D. The Double Helix: A Personal Account of the Discovery of the Structure of
DNA (Athenaeum, New York, 1968).
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Klug, A. (1968) Nature 219:808-810; 843-844.
Klug, A. (1974). Rosalind Franklin and the double helix. Nature 248:787-788.
Fuller, W. (2003). Who said 'helix'? Nature 424:876 – 878.
Judson, H.F. (1996) - The Eighth Day of Creation: The Makers of the Revolution in
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Prusiner, S.B. (1998) Prions. Proc. Natl. Acad. Sci. 95:13363-13383.
Collinge J. (2001). Prion diseases of humans and animals: their causes and molecular
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Soto, C., and Castilla, J. (2004). The controversial protein-only hypothesis of prion
propagation. Nature Medicine 10:S63–S67.
Gurdon JB, Byrne JA, Simonsson S (2003). Nuclear reprogramming and stem cell
creation. Proc Natl Acad Sci U S A. 100 (Suppl 1):11819-22.

2) 原始文献

Mendel, G. (1865) Experiments in Plant Hybridization

Read at the meetings of February 8th, and March 8th, 1865
http://www.mendelweb.org/Mendel.html
Beadle, G. W. and Tatum, EL. (1941). Genetic Control of Biochemical Reactions in
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Chromosomes and DNA

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DNA Structure
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The Genetic Code

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Protein Synthesis and tRNA

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mRNA
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DNA Synthesis
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Bacterial Genetics
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Restriction Enzymes
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Prions
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Homologous recombination
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RNA Interference

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Ion Channels
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