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--- History of Molecular Biology

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1 --- History of Molecular Biology
The Story of DNA --- History of Molecular Biology “History Teaches Everything, Including the Future.” --- Alphonse de Lamartine

2 Genetics Biochemistry Cell biology Microbiology Virology

3 DNA Overview of the History of Molecular Biology ……
1929 – the chemical components of DNA 1940 – the relationship between genes and proteins 1944 – Genes are made up of DNA 1953 – the double helical structure of the DNA molecule (Watson and Crick) 1957 – the “Central Dogma” and the “sequence hypothesis” (Crick) 1958 – the mechanism of DNA replication 1961 – the hypothesis of the messenger RNA (mRNA) 1961 to 1965 – the genetic code was deciphered …… 1970s to 80s – DNA cloning, sequencing and genetic engineering 1990s to 2000s – genome sequencing and functional study of genes DNA In the early days of the history, people first identified the chemical components of DNA (the four bases, the sugar and the phosphate chain), and later, discovered the existence of a precise relationship between genes and proteins. A few years later, people demonstrated that genes are made up of DNA. Not long after that, Watson and Crick discovered the double helical structure of the DNA molecule. Later, “Central Dogma” was brought up, which describes the relationship between DNA, RNA, and proteins. Soon after that, people got to understand the mechanism of DNA replication, and how DNA passes on genetic information to messenger RNA, and to proteins. All these earlier research laid the basis for modern molecular biology to be able to manipulate DNA and read genome (the entire set of DNA in an organism).

4 DNA cloning and genetic engineering
Overview of the History of Molecular Biology DNA cloning and genetic engineering Discovery of DNA Genes and DNA DNA - RNA - protein Genome era 1930 1940 1950 1960 1970 1980 1990 2000 There are 5 stages in the history: the discovery of the existence of DNA, which starts before the 20th century; the realization of DNA as the gene bearer in 1940s, a detailed understanding about DNA and its function between 1950s to 70s, followed by a rapid advance in molecular biology techniques that enables DNA cloning and genetic engineering, and the last decade of the 20th century until now, the genome era.

5 The search of genetic material
Discovery of DNA DNA cloning and genetic engineering Genes and DNA DNA - RNA - protein Genome era 1930 1940 1950 1960 1970 1980 1990 2000 The discovery of DNA Hofmeister (1848): discovery of chromosomes Miescher (1868): “nuclein” = DNA + protein Chromosome theory of inheritance Mendel (1865): Laws of inheritance Morgan (1910): Genes are on chromosomes Who carries genetic material, DNA or proteins?

6 How did people know that DNA carries genetic information?
Discovery of DNA DNA cloning and genetic engineering Genes and DNA DNA - RNA - protein Genome era 1930 1940 1950 1960 1970 1980 1990 2000 Avery, Macleod and McCarty’s experiment (1943)

7 Griffith’s Experiment

8 Avery, Macleod and McCarty’s experiment (1943)

9 Avery’s Experiment on Pneumococcus:
A) What was the original observation that Avery made in test tubes? B) List two hypotheses based on the observation (doesn’t matter if they are right or wrong). C) What predictions would you make based on each of the hypotheses?

10 How did people know that DNA carries genetic information?
Discovery of DNA DNA cloning and genetic engineering Genes and DNA DNA - RNA - protein Genome era 1930 1940 1950 1960 1970 1980 1990 2000 Avery, Macleod and McCarty’s experiment (1943)

11 DNA cloning and genetic engineering
The Double Helix Discovery of DNA DNA cloning and genetic engineering Genes and DNA DNA - RNA - protein Genome era 1930 1940 1950 1960 1970 1980 1990 2000 Crick and Watson: theoretical model Wilkins and Franklin: X-ray diffraction First accurate model of DNA's molecular structure (1953) Nobel Prize, 1962 "Why You Are You. Nearer Secret of Life." --The News Chronicle of London Watson Crick Wilkin Franklin

12 Rosalind Franklin: The Dark Lady of DNA
A British Biophysicist Specialized in X-ray crystallography King’s College, London ( ): - Worked with Maurice Wilkin and Raymond Gosling Form A and B of DNA Photograph 51 ”The Eighth Day of Creation: Makers of the Revolution in Biology“ by Horace Freeland Judson

13 From DNA to Proteins 1957 – the “Central Dogma” (Crick)
Discovery of DNA DNA cloning and genetic engineering Genes and DNA DNA - RNA - protein Genome era 1930 1940 1950 1960 1970 1980 1990 2000 Reverse transcriptase 1957 – the “Central Dogma” (Crick) 1958 – the mechanism of DNA replication 1961 – the hypothesis of the messenger RNA 1961 to 1965 – the genetic code was deciphered Howard Temin (Nobel Prize 1975)

14 DNA cloning and genetic engineering
The Golden Age of Molecular Biology Discovery of DNA DNA cloning and genetic engineering Genes and DNA DNA - RNA - protein Genome era 1930 1940 1950 1960 1970 1980 1990 2000 1969: First gene in bacterial DNA isolated 1970: First synthetic (artificial) gene 1973: First successful DNA cloning experiment 1977: DNA is sequenced 1978: The first human gene is cloned – insulin 1982: Genetically-engineered insulin is approved for use 1985: PCR (Polymerase Chain Reaction) is invented Har Gobind Khorana (Nobel Prize 1968) Har Gobind Khorana shared the Nobel Prize in Physiology or Medicine in 1968 with Marshall W. Nirenberg and Robert W. Holley for research that helped to show how the nucleotides in nucleic acids, which carry the genetic code of the cell, control the cell’s synthesis of proteins.

15 DNA cloning and genetic engineering
The Golden Age of Molecular Biology Discovery of DNA DNA cloning and genetic engineering Genes and DNA DNA - RNA - protein Genome era 1930 1940 1950 1960 1970 1980 1990 2000 1996: First genome sequenced – S. cerevisae (yeast) 1997: Bacteria E. coli genome sequenced 1998: C. elegans (worm) sequenced 2000: Drosophila (fruit fly) sequenced 2002: Mouse sequenced 2001: First draft sequences of the human genome are released (Human Genome Project) 2003: Completion of the mapping of the genes in the human genome Fred Blattner

16 What can we do with DNA? Genetic engineering - Use model organisms to study genes and functions - Make transgenic organisms Applications for human - Forensics, paternity testing - Genetic diagnosis and prevention of diseases (Genetic counseling) - Gene therapy

17 DNA and The Revolution in Personalized Medicine
Your life depends on the secret of your DNA… Personalized Medicine - Genetic screening for prevention (newborn screening, carrier screening, maternal screening, Pre-implantation Genetic Diagnosis (PGD)) - Risk prediction - The right drug at the right dose for the right person Together with environmental factors, your DNA determines, or largely affects your health. Besides many well-known genetic diseases such as Down’s syndrome, color blindness, hemophilia, etc, more and more diseases have been shown to be genetically related. For example, cancer is a disease of DNA. Diabetes is a disease of DNA. Alzheimer’s disease is a disease of DNA. Everyone of us has glitches in our DNA, and that can tell a lot of the future of your life. Our DNA determines the predisposition and the susceptibility to a certain disease, and the response to a certain drug or treatment for the disease. If we can now read our DNA instruction book, we could probably do a lot better in diagnosis and prevention of diseases, and make more effective treatment. The completion of HGP leads to a revolution in personalized medicine. The rationale is, as apposed to the traditional medicine, which treat patients with the same disease in the same way with the same set of drugs, we should take genetics into account.

18 Fields Related to Modern Molecular biology
Molecular genetics Cell Biology Developmental Biology Genomics Bioinformatics Biophysics and Structural Biology Population and evolutionary biology

19 Next class: Case Study: The Human Genome Project and Designer Baby Discussion of Molecular biology research groups on campus – What do they do and why?


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