The Nobel Prize in Medicine - 1968

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The Nobel Prize in Medicine - 1968
A presentation on

• By,
• Anusha Teegala

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Nobel Prizes 1968
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The beginning of Genetics as a Science

• Exactly 100 years back since 1968.
• 1866 - Gregor Mendel Discovers from very simple
  experiments with peas that our inheritance is
  packaged into many independent genes.
• 1868 - Friedrich Miescher (Father of genetics) -
  isolated nucleic acid from cell nuclei.
• 1944 - Avery - Link established Genes contain
  nucleic acids.
• Nucleic acids - composed of nucleotide chains
  that convey genetic information.
• Genes Has a sequence of codons which inturn
  specify the amino-acid sequence of the encoded
  protein.

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Genetic Code of Life

• What is Genetic Code?
• Set of rules by which information encoded in
  genetic material (DNA or RNA sequences) is
  translated into proteins (amino acid sequences)
  by living cells.
• Why is it called the code of Life?
• These rules describes all our inherited traits.
• The genetic code is the dictionary that
  translates the nucleic alphabets to corresponding
  protein alphabets
• Aim To crack the code Our three musketeers to
  the rescue.

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Marshall W. Nirenberg

• Devises a translation-machine
• Feed this machine with nucleic acid alphabets and
  it returns corresponding alphabets in protiens.
• Synthesized a very simple nucleic acid, composed
  of a chain of only a single repeating letter.
  Using this nucleic acid the system produced a
  protein which also contained a single letter, now
  written in the protein alphabet.

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Nirenbergs Research Approach

• Various combinations of mRNA were passed through
  a filter which contained ribosomes.
• Unique triplets promoted the binding of specific
  tRNAs to the ribosome.
• By associating the tRNA with its specific amino
  acid, it was possible to determine the triplet
  mRNA sequence that coded for each amino acid.
• He got the wheel rolling In less than five
  years, along with Khorana, establishes the
  Genetic Code.
• Presently involved in investigation of various
  aspects of neurobiology.

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Har Gobind Khorana

• Systematically devises methods which led to the
  synthesis of well defined nucleic acids, giant
  molecules with every building block in its exact
  position.
• His synthetic nucleic acids were a pre-requisite
  for the final solution of the genetic code.
• Currently At MIT, Works on molecular mechanisms
  of visual transduction in the vertebrate
  photoreceptor cells.
• Trivia - Khorana, US Citizen.

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Khoranas Research Approach

• (RNA) with two repeating units (UCUCUCU ? UCU CUC
  UCU) produced two alternating amino acids. This,
  combined with the Nirenberg and Leder experiment,
  showed that UCU codes for Serine and CUC codes
  for Leucine.
• RNAs with three repeating units (UACUACUA ? UAC
  UAC UAC, or ACU ACU ACU, or CUA CUA CUA) produced
  three different strings of amino acids.
• RNAs with four repeating units including UAG,
  UAA, or UGA, produced only dipeptides and
  tripeptides thus revealing that UAG, UAA and UGA
  are stop codons.

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Invention of Khorana - Oligonucleotides

• Oligonucleotides Short strings of nucleotides,
  custom built artificial genes.
• Oligonucleotides are often used as probes for
  detecting complementary DNA or RNA because they
  bind readily to their complements
• widely used in biology labs for sequencing,
  cloning and engineering new plants and animals.
• Composed of DNA, are often used in the polymerase
  chain reaction (PCR), a procedure that can be
  employed to amplify almost any piece of DNA.
• This invention of Dr. Khorana has become
  automated and commercialized so that anyone now
  can order a synthetic gene from any of a number
  of companies-- one merely needs to fax the
  genetic sequence to one of the companies to
  receive an oligonucleotide with the desired
  sequence.
• Further reference can be found at
  http//www.bio.davidson.edu/Courses/Molbio/MolStud
  ents/spring2003/Holmberg/oligonucleotide_synthesis
  .htm

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Robert W. Holley

• What is the mechanism for the translation of the
• code within the cell?
• He is one of the discoverers of a special type of
  nucleic acid which has been called transfer-RNA.
• tRNA - has the capacity to read off the genetic
  code and to transform it to the protein alphabet.
  
• After many years of work Holley succeeds in
  preparing a tRNA in pure form, in 1965,
  established its exact chemical structure.
• Holley's work represents the first determination
  of the complete chemical structure of a
  biologically active nucleic acid.

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Holleys Research Approach

• Holley's team of researchers determined the
  tRNA's structure by using two ribonucleases to
  split the tRNA molecule into pieces. Each enzyme
  split the molecule at location points for
  specific nucleotides.
• By a process of "puzzling out" the structure of
  the pieces split by the two different enzymes,
  then comparing the pieces from both enzyme
  splits, the team eventually determined the entire
  structure of the molecule.

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Trivia

• 1958 Nobel Laureate, Edward Tatum (discovered
  that the genes control production of enzymes)
  predicted that it might take a lifetime to crack
  the code. But these three scientists take the
  bio-community by surprise, they crack the code in
  less than three years.
• Part of chapter 2 is all thanks to them.
• How far have we come since 1968?
• Conviction based on DNA Finger printing
• Genetically engineered food
• Dolly First adult animal clone

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Thank you!

• Questions?
• References,
• Nobelprize.org
• Wikipedia.org