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Slide1: FROM THE DISCOVERY OF THE HELIX TO STRUCTURAL GENOMICS Challenges for the future Rien de Bie Bijvoet Center for Biomolecular Research Utrecht, The Netherlands
What is Life: What is Life
What is Life?: What is Life? Erwin Schrödinger (1944):
Life can be thought of in terms of storing and passing on biological information.
Chromosomes are information bearers.
The huge amount of information is compressed in a “heriditary code-script” embedded in the molecular fabric of the chromosomes.
To understand life, we have to identify these molecules and crack the code.
Oswald Avery, Maclyn McCarthy and Colin MacLeod (1944):
They showed in a beautiful series of experiments that DNA is the substance inducing transformation of pneumococcal types.
This discovery leads directly to conclusion that the “heriditary code-script” is embedded in DNA.
No Nobel was awarded for this pivotal discovery because one member of the Nobel committee fought consistently for many years against this conclusion.
The paper: The paper
The model: The model
The base pairs: The base pairs
Maurice Wilkins: Maurice Wilkins M.H.F. Wilkins, A.R. Stokes, H.R. Wilson:
Molecular Structure of Deoxypentose Nucleic
Acids. Nature 171, 738 (1953)
Rosalind Franklin: Rosalind Franklin
R.E. Franklin and R.G. Gosling
Molecular Configuration in Sodium
Thymonucleate, Nature 171, 740 (1953)
The Meselson-Stahl experiment: The Meselson-Stahl experiment
Frederick Sanger (Nobel 1958): Frederick Sanger (Nobel 1958)
Severo Ochoa, Arthur Kornberg (Nobel 1959): Severo Ochoa, Arthur Kornberg (Nobel 1959)
Nobel laureates 1962: Nobel laureates 1962 Wilkins, Perutz, Crick, Steinbeck, Watson, Kendrew
Citations: Citations DNA Publication never became a hot paper
Citations/year
Perutz (Haemoglobin), Kendrew (Myoglobin): Perutz (Haemoglobin), Kendrew (Myoglobin)
Myoglobine structure: Myoglobine structure
Location, Location, Location: Location, Location, Location
DNA folding-1: DNA folding-1
DNA folding-2: DNA folding-2
DNA replication: DNA replication
From DNA to protein: From DNA to protein
Exons and Introns (1977) Roberts and Sharp (Nobel 1993): Exons and Introns (1977) Roberts and Sharp (Nobel 1993) A precursor-RNA may often be matured to
mRNAs with alternative structures. An example
where alternative splicing has a dramatic
consequence is somatic sex determination in the
fruit fly Drosophila melanogaster.
In this system, the female-specific sxl-protein
is a key regulator. It controls a cascade of
alternative RNA splicing decisions that finally
result in female flies.
Building a complex: Building a complex
Ribosome: Ribosome
Sequencing Sanger, Gilbert (Nobel 1980): Sequencing Sanger, Gilbert (Nobel 1980)
Venter, Clinton, Collins (2001) Draft sequence from Celera and IHGSC: Venter, Clinton, Collins (2001) Draft sequence from Celera and IHGSC
Chromosome 20: Chromosome 20
H. Influenza gene: H. Influenza gene
Structural Tools: Structural Tools
Richard Ernst (Nobel 1991): Richard Ernst (Nobel 1991)
Kurt Wüthrich (Nobel 2002): Kurt Wüthrich (Nobel 2002)
Prion Structure: Prion Structure
Robotics: Robotics
Proteomics on 2D-gel: Proteomics on 2D-gel
DNA Repair: DNA Repair
DNA Repair-2: DNA Repair-2
Model of a part of the DNA repair protein UvrC with a SS/DS DNA: Model of a part of the DNA repair protein UvrC with a SS/DS DNA
Live Wire: Live Wire
The histone code: The histone code
Tamm-Horsfall protein: Tamm-Horsfall protein
Carbohydrate chains: Carbohydrate chains
John Maddox: John Maddox
Acknowledgements: Acknowledgements This lecture is based on material obtained from various sources:
James D. Watson: DNA, the secret of life (2003)
James D. Watson: The Double Helix (1968)
John Maddox: What remains to be discovered (1998)
Brenda Maddox: Rosalind Franklin: The dark lady of DNA (2002)
Tyler Wasson ed.: Nobel Prize Winners (1987)
John C. Kendrew: The three-dimensional structure of a protein molecule. Scientific American 196112, 96-110
Nature, January 2003: The double Helix, 50 years
New Scientist, March 2003: DNA, The next 50 years
Nature Insight: Proteomics (January 2003)
http://www.nobel.se
Members of the Bijvoet Center: L.J. Braakman, J.P. Kamerling, R. Boelens