分子生物学1 --分子生物学的发展

Questions surround Mendel’s findings
• Mendel’s ideas seem obvious today. This was not the case in the past. No one had ever heard of a “gene” in Mendel’s time. • Biologists previously failed to distinguish between heredity and development.
•分子生物学不是单一界 限分明的学科
Dr. F.Crick 谈到自己的研究 领域时：“我……勉强称自己 为分子生物学家，因为爱打听 的牧师问我做什么工作时，我 已经为解释自己兼为结晶学家、 生物物理学家、生物化学家和 遗传学家而感到厌烦……”
What is the gene?
Mendel: The Father of Genetics
生物学的昨天、今天和明天
• 现代生物学的开端：
• 显微镜——细胞 • 电子显微镜 • X-ray晶体衍射——分子
• 分子生物学的涵义
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分子生物学（Molecular Biology) 顾名思义： 在分子水平上研究生命过程的科学。 分子生物学研究是在分子水平上研究基因和基 因的活动，是对遗传学内容的新理解，von Laue reported the diffraction of X rays by a crystal (for which he received a Nobel Prize in physics in 1914)
• For progress in pharmaceutical research the structure of complex organic molecules has to be understood • By studying the chemical reactions that a compound and its degradation products could enter into with other compounds of known structure, chemists were able to deduce the structures of many complex organic molecules
• He observed that inherited diseases reflect a patient's inability to make a particular enzyme, which he referred to as “inborn errors of metabolism” • Garrod's hypothesis was ahead of its time • In the 1930s George Beadle and Boris Ephrussi linked the synthesis of pigments to eye color in fruit flies to specific mutations
• The relationship between genes and proteins was first proposed by Garrod in 1908 • Garrod, a prominent physician at St. Bartholomew's Hospital in London, understood both the new science of biochemistry and the emerging discipline of genetics
大连医科大学生化与分子生物学教研室
刘 煜
生物学的昨天、今天和明天
• 生物学的定义：
一门关于生命的科学
生物学家需要在许多层次进行他们的研究
原子——分子——细胞——组 织——器官——有机体——群落
生物学的昨天、今天和明天
• 人是一架机器吗？
• 中世纪 • 机械论者与活力论者的持久争执
1628年威廉.哈维发现血液循环 1828年弗里德里希.味勒在实验室合成了尿素
1910-1925: 细胞遗传学的进展
• Cytogenetics is the study of chromosomes and chromosome abnormalities
X-ray衍射晶体分析法
• X-ray crystallography is a technique that exploits the fact that X-rays are diffracted by crystals • It is not an imaging technique: X-rays have the proper wavelength to be scattered by the electron cloud of an atom of comparable size • Based on the diffraction pattern obtained from Xray scattering off the periodic assembly of molecules or atoms in the crystal, the electron density can be reconstructed
• Named the substance nuclein （核素）because it seemed to come from cell nuclei. In 1874 when Miescher separated it into a protein and an acid molecule. It is now known as deoxyribonucleic acid (DNA) • This substance was so unusual that Hoppe-Seyler repeated the work himself before allowing Miescher to publish the paper on the discovery
• Made brilliant insights into heredity. • Began classical experiments into heredity involving pea plants beginning in 1854. • Established Principle of Segregation as well as the concept of dominant and recessive traits.
研究的主要内容：Three Major Approaches
1. 2. 3. Structural (architecture of the molecules) Biochemical (interactions between cell metabolism and heredity) Informational (transfer of information, translation of information)
• Following Mendel’s laws, Garrod concluded that alkaptonuria is a congenital disorder, not the result of a bacterial infection as was commonly thought
“nucleic acid”
先天性代谢障碍
• Archibald Garrod (British, 1857-1936) • His father was a physician • Received his medical training at St. Bartholomew's Hospital, London
发现 DNA
• Friedrich Miescher (Swiss, 1844-1895) • Intelligent from early age but very shy • His father was a professor of anatomy • Studied at the University of Göttingen under Ernst Felix Immanuel Hoppe-Seyler, considered the father of biochemistry
• He studied a harmless but rare disorder in the general population but frequent in children of first-cousin marriages: alkaptonuria（尿黑酸尿症） • A patient with this disorder produces urine that when exposed to air turns distinctively dark, because these people lack the enzyme found in normal individuals who are able to convert the reddening agent, alkapton（尿黑酸）, to another substance
• He found an excellent (and more pleasant) source of nuclear material in the sperm of the salmon • The nuclei are large in any sperm cells, remarkably so in the salmon’s • From these he first extracted a pure DNA • In 1889 a pupil of his, the German pathologist Richard Altmann (1852-1900) introduced the term
• He examined used bandages obtained from a hospital caring for the wounded of the Crimean War in hope of finding something interesting • He discovered a substance containing both phosphorus and nitrogen, made up of molecules that were apparently very large, in the nuclei of white blood cells found in pus
• X-ray crystallography allowed to determine molecular structure from the compound itself. In this method, structural information is obtained by mathematical analysis of the intensity of X rays scattered (or diffracted) from parallel planes in a crystal, as recorded photographically or by an electronic detector • In 1915 a unique father-son team, William Henry Bragg (1862–1942) and his son, William Lawrence Bragg (1890–1971), won the Nobel Prize in physics for their seminal roles in X-ray crystallography