lecture#1 btc 563 “ if the ultimate aim of science is to clarify mankind’s relationship to the...

BTC 563BTC 563 Lecture#1Lecture#1

“ “ IF THE ULTIMATE AIM OF SCIENCE IS TO IF THE ULTIMATE AIM OF SCIENCE IS TO CLARIFY MANKIND’S RELATIONSHIP TO CLARIFY MANKIND’S RELATIONSHIP TO THE UNIVERSE , THEN THE UNIVERSE , THEN BIOLOGYBIOLOGY MUST BE MUST BE GIVEN A GIVEN A CENTRALCENTRAL POSITION” POSITION”

Jacques Manod ,Nobel prizeJacques Manod ,Nobel prize

(allosteric transitions)(allosteric transitions)


ScientifiScientifi

c c discoverdiscover

y y inin

moleculmolecular ar

biology biology


MOLECULAR MOLECULAR BIOLOGYBIOLOGY

BIOCHEMISTRYBIOCHEMISTRY

CELL BIOLOGYCELL BIOLOGY

GENETICSGENETICS

MOLECULAR MOLECULAR BIOLOGYBIOLOGY


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1632-1723 1632-1723 Antony van Antony van LeeuwenhoekLeeuwenhoek – –

shopkeeper, Dutchshopkeeper, Dutch


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1635-1703 1635-1703 RobertRobert Hooke Hooke – physicist, London– physicist, London

MicrographiaMicrographia, published in 1665, published in 1665

. . . I could exceedingly plainly perceive it to be all perforated and porous, much like a Honey-comb, but that the pores of it were not regular. . . . these pores, or cells, . . . were indeed the first microscopical pores I ever saw, and perhaps, that were ever seen, for I had not met with any Writer or Person, that had made any mention of them before this. . .


1800-18821800-1882 Friedrich Friedrich WöhlerWöhler - -

German chemistGerman chemist synthesized a synthesized a

natural product - natural product - urea (1828)urea (1828)

Bridge between Bridge between living/non-livingliving/non-living

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Urea CycleUrea Cycle Urea - nitrogenous waste of mammals. Urea - nitrogenous waste of mammals. Comes from the breakdown of amino acidsComes from the breakdown of amino acids

Ammonia - extremely toxic base and its Ammonia - extremely toxic base and its accumulation in the body would quickly be fatal. accumulation in the body would quickly be fatal.

The The liverliver contains a system of carrier molecules contains a system of carrier molecules and enzymes which converts the ammonia (and and enzymes which converts the ammonia (and carbon dioxide) into urea. carbon dioxide) into urea.


UreaUrea Industrial use - the manufacture of Industrial use - the manufacture of

plastics (specifically, urea-formaldehyde plastics (specifically, urea-formaldehyde resin), a component of many fertilizers, resin), a component of many fertilizers, providing a nitrogen source that is providing a nitrogen source that is necessary for plants. necessary for plants.

Laboratory use - a powerful protein Laboratory use - a powerful protein denaturant. denaturant.

Medical significance - high levels of Medical significance - high levels of urea in the blood indicate a problem urea in the blood indicate a problem with the removal, or more rarely with with the removal, or more rarely with the over-production, of urea in the the over-production, of urea in the body. body.


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1773 – 18581773 – 1858 Robert Robert BrownBrown-Scottish botanist -Scottish botanist

Found nucleus (1825)Found nucleus (1825) Brownian MovementBrownian Movement


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1804-1881 1804-1881 Matthias Matthias SchleidenSchleiden -German botanist -German botanist 1810-1882 1810-1882 Theodor Theodor SchwannSchwann - German cytologist , - German cytologist ,

physiologistphysiologist Developed the cell theory in Developed the cell theory in 18391839, which identified , which identified

cells as the fundamental particles of plants and cells as the fundamental particles of plants and animals animals


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1821-1902 1821-1902 Rudolf Rudolf VirchowVirchow - German pathologist - German pathologist

"Omnis cellula e cellula" (where a cell arises, "Omnis cellula e cellula" (where a cell arises, there a cell must previously have existed).there a cell must previously have existed). ((18581858) )


1822-18951822-1895 Louis Louis PasteurPasteur –French –French chemistchemist

Solved the mysteries of rabies, anthrax, chicken Solved the mysteries of rabies, anthrax, chicken cholera, and silkworm diseases, and contributed cholera, and silkworm diseases, and contributed to the development of the first to the development of the first vaccinesvaccines

Reason for fermentation (Reason for fermentation (yeastyeast))

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1823-1884 1823-1884 Gregor Gregor MendelMendel – Czech monk – Czech monk

Fundamental laws of Fundamental laws of geneticsgenetics (1865) (1865)

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1844-1895 1844-1895 Friedrich Friedrich MiescherMiescher - Swiss physician - Swiss physician

isolated nucleic acidisolated nucleic acid became known as nucleic acid after became known as nucleic acid after 18741874, when , when

Miescher separated it into a protein and an acid Miescher separated it into a protein and an acid molecule. molecule.

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1843-1905 1843-1905 Walter Walter FlemmingFlemming - German scientist - German scientist

1870 Discovered 1870 Discovered chromosomes chromosomes 1871 Discovered 1871 Discovered mitosismitosis Linked mitosis to Mendel’s observationsLinked mitosis to Mendel’s observations

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1860-1917 1860-1917 Eduard & Hans Eduard & Hans BuchnersBuchners– German – German

brothersbrothers

Eduard Buchner Winner of the 1907 Eduard Buchner Winner of the 1907 Nobel Prize in ChemistryNobel Prize in Chemistry

1897 - Discovery of 1897 - Discovery of cell-free cell-free fermentationfermentation

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1862 - 19151862 - 1915 Theodor Theodor BoveriBoveri – German biologist – German biologist

1877-19161877-1916 Walter Walter Sutton Sutton - graduate student in the - graduate student in the

Department of ZoologyDepartment of Zoology ((19021902) chromosome theory of ) chromosome theory of HeredityHeredity

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19201920

Nucleic Acids major component of Nucleic Acids major component of chromosomeschromosomes

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1881 – 19551881 – 1955 Sir Alexander Sir Alexander FlemingFleming

Nobel Prize in 1945. Nobel Prize in 1945. "One sometimes finds what one is not "One sometimes finds what one is not

looking for." looking for." He published a report on penicillin He published a report on penicillin

1929,but it raised little interest 1929,but it raised little interest

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19271927 James James SumnerSumner – American – American

biochemistbiochemist Purified and crystallized the Purified and crystallized the

first protein enzyme first protein enzyme (urease from bean)(urease from bean)

1946 - Nobel Prize for 1946 - Nobel Prize for Chemistry Chemistry

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1881 - 1941 1881 - 1941

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FrederickFrederick Griffith Griffith -an English army -an English army medical officermedical officer

inin 19281928 Discovered “Genetic Discovered “Genetic TransformationTransformation””


Frederick Griffith’s 1920s Frederick Griffith’s 1920s ExperimentExperiment


1877-1955 1877-1955 Oswald Oswald AveryAvery – American bacteriologist – American bacteriologist

19431943 – proved that – proved that DNADNA carries genes carries genes

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SS RR

DNA

SS


Discovery of DNADiscovery of DNA

the extracts of heat-killed S bacteria cellsthe extracts of heat-killed S bacteria cells containedcontained proteinprotein, , RNARNA and and DNADNA which of these substances were essential which of these substances were essential

for transformation?for transformation?

How did they figure out which substance How did they figure out which substance was essential for transformation?was essential for transformation?


Discovery of DNADiscovery of DNA

They decided to use the process of They decided to use the process of eliminationelimination

Extracts were treated with either Extracts were treated with either Proteases (to destroy protein)Proteases (to destroy protein) RNase (to destroy RNA)RNase (to destroy RNA) DNase (to destroy DNA)DNase (to destroy DNA)

Transformation was due Transformation was due exclusively to exclusively to DNADNA


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Alfred Alfred HershyHershy and Martha and Martha ChaseChase

1952 1952 used bacteriophage to prove thatused bacteriophage to prove that

DNA was the hereditary material DNA was the hereditary material the bacteriophage was the the bacteriophage was the idealideal

organism for organism for

settling the debate between protein settling the debate between protein and DNA. and DNA.


What are viruses?What are viruses? Viruses are Viruses are

organized organized associations of associations of macromolecules:-macromolecules:-nucleic acid nucleic acid contained within a contained within a protectiveprotective shell of shell of protein units .protein units .

A virus isA virus is NOT alive. NOT alive.A virus isA virus is NOT made NOT made out of a cell.out of a cell.


DNA discovery DNA discovery Hersy-Chase Hersy-Chase 1952 1952


DNA discovery DNA discovery Hersy-ChaseHersy-Chase 1952 1952


1929-19921929-1992 Erwin Erwin ChargaffChargaff – –

Austrian American Austrian American biochemist biochemist (1950) Discovered the (1950) Discovered the

base-pairing regularities base-pairing regularities or "or "complementaritycomplementarity relationships" of nucleic relationships" of nucleic acids that provided one acids that provided one of the key steps in of the key steps in developing a structural developing a structural model for DNA. model for DNA.

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1920 – 19581920 – 1958 Rosalind Rosalind FranklinFranklin- English - English

ChemistChemist the most beautiful the most beautiful X-rayX-ray

photographs of any photographs of any substance ever taken substance ever taken

(1952) crucial contributions (1952) crucial contributions to the solution of the to the solution of the structure of DNA structure of DNA

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1953 1953 James James WatsonWatson – American ornithologist – American ornithologist Francis Francis CrickCrick – British Physicist – British Physicist

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19551955Fred Fred SangerSanger- British Biochemist- British Biochemist

The Nobel Prize in Chemistry The Nobel Prize in Chemistry 19581958 First First complete sequence of the proteincomplete sequence of the protein

(insulin)(insulin) The Nobel Prize in Chemistry 1980The Nobel Prize in Chemistry 1980

"for their contributions concerning the "for their contributions concerning the determination of base sequences in determination of base sequences in nucleic acids" nucleic acids"

Principle of the Chain-terminating Principle of the Chain-terminating (dideoxy Method for (dideoxy Method for Sequencing DNASequencing DNA

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Marshall W. Marshall W. NirenbergNirenberg Heinrich Heinrich MathieuMathieu

protein synthesis protein synthesis poly-Upoly-U experiments and the first experiments and the first clue to the genetic code clue to the genetic code

19681968 - Nobel Laureate in - Nobel Laureate in Medicine Medicine

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19801980 Paul Paul BergBerg, Walter , Walter GilbertGilbert, Frederick , Frederick

SangerSanger The Nobel Prize in Chemistry 1980The Nobel Prize in Chemistry 1980 "for their contributions concerning the "for their contributions concerning the

determination of base determination of base sequences in sequences in nucleic acidsnucleic acids" "

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19781978 David David BotsteinBotstein - California - California

Discovery of Restriction EnzymesDiscovery of Restriction Enzymes


19771977 Bill Bill Rutter Rutter and Howard and Howard GoodmanGoodman

Isolated the gene for rat insulin Isolated the gene for rat insulin

19781978 HarvardHarvard researchers used genetic researchers used genetic

engineering techniques to engineering techniques to produce rat produce rat insulininsulin

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Kary B. Kary B. MullisMullis

19801980

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1980 - Kary B. 1980 - Kary B. MullisMullis Cetus Corporation in Berkeley, Cetus Corporation in Berkeley,

California, invented a technique for California, invented a technique for multiplying DNA sequences in vitro by, multiplying DNA sequences in vitro by, the polymerase chain reaction - the polymerase chain reaction - PCRPCR. . PCR has been called the most PCR has been called the most revolutionary new technique in revolutionary new technique in molecular biology in the 1980s. Cetus molecular biology in the 1980s. Cetus patented the process, and in the patented the process, and in the summer of 1991 sold the patent to summer of 1991 sold the patent to Hoffman-La Roche, Inc. for $300 millionHoffman-La Roche, Inc. for $300 million

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The idea was not the product of a painstaking The idea was not the product of a painstaking laboratory discipline, but was conceived while laboratory discipline, but was conceived while cruising in a cruising in a HondaHonda Civic on Highway 128 from San Civic on Highway 128 from San Francisco to Mendocino. Francisco to Mendocino.

"I do my best thinking while driving," the scientist "I do my best thinking while driving," the scientist with the tanned face and bleached hair once with the tanned face and bleached hair once explained. For this brilliant idea born at the speed explained. For this brilliant idea born at the speed of 50 m.p.h., he received a $10,000 bonus from of 50 m.p.h., he received a $10,000 bonus from Cetus, with whom he eventually parted ways. Cetus, with whom he eventually parted ways. (Cetus later sold the technolgy to LaRoche for (Cetus later sold the technolgy to LaRoche for $300,000,000.) He now lives in a small apartment $300,000,000.) He now lives in a small apartment across from Windansea Beach, a surfing spot made across from Windansea Beach, a surfing spot made famous by Tom Wolfe's novel, "The Pump House famous by Tom Wolfe's novel, "The Pump House Gang." A man interested in many things in life Gang." A man interested in many things in life besides molecular biology and surfing, he has besides molecular biology and surfing, he has refused to team up with the biotechnology industry refused to team up with the biotechnology industry or academia. Currently, he consults and lectures or academia. Currently, he consults and lectures around the world about biotechnology or the around the world about biotechnology or the development of the scientific method, its development of the scientific method, its successes and its failures.successes and its failures.


19831983 Jay Levy's lab at Jay Levy's lab at University of University of

California San FranciscoCalifornia San Francisco and Pasteur and Pasteur Institute in Paris and at the NIH Institute in Paris and at the NIH isolated isolated thethe AIDS virusAIDS virus

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19861986 A regiment of scientists and A regiment of scientists and

technicians at Caltech and Applied technicians at Caltech and Applied Biosystems, Inc., invented the Biosystems, Inc., invented the automated DNA fluorescence automated DNA fluorescence sequencer sequencer

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19901990 Mary Claire Mary Claire KingKing, ,

epidemiologist at UC-epidemiologist at UC-BerkeleyBerkeley reported the discovery reported the discovery

of the of the genegene linked to linked to breastbreast cancercancer in families in families with a high degree of with a high degree of incidence before age 45. incidence before age 45.

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19971997 Researchers at Scotland's Roslin Researchers at Scotland's Roslin

Institute report that they have cloned a Institute report that they have cloned a sheep--named sheep--named DollyDolly - from the cell of - from the cell of an adult ewe. Polly the first sheep an adult ewe. Polly the first sheep cloned by nuclear transfer technology cloned by nuclear transfer technology bearing a human gene appears later.bearing a human gene appears later.

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19991999 ““Celera genomics” – Rockville, MarylandCelera genomics” – Rockville, Maryland

Drosophila genomeDrosophila genome

http://www.fruitfly.org/http://www.fruitfly.org/

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20002000 Complete Complete HumanHuman Genome Project Genome Project

http://www.genome.gov/http://www.genome.gov/

20022002 MouseMouse Genome Project Genome Project

http://www.informatics.jax.org/http://www.informatics.jax.org/

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Physicists developed the most Physicists developed the most powerful techniques used by powerful techniques used by biochemists:biochemists:

Electron microscopyElectron microscopy X-ray diffractionX-ray diffraction Nuclear Magnetic ResonanceNuclear Magnetic Resonance


FUTURE PROGRESSFUTURE PROGRESS

DEVELOPMENT AND DEVELOPMENT AND DIFFERENTIATIONDIFFERENTIATION

BRAIN FUNCTIONBRAIN FUNCTION MOLECULAR BASES FOR ALL MOLECULAR BASES FOR ALL

DISEASES DISEASES

NOBELNOBEL

http://www.nobel.se/

lecture#1 btc 563 “ if the ultimate aim of science is to clarify mankind’s relationship to the...

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s slide

dutch slide

urea industrial use

natural product urea

ureaformaldehyde resin

laboratory use

london robert hooke

nobel prize jacques