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Published on October 16, 2007

Author: WoodRock



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) Members of the Bijvoet Center: L.J. Braakman, J.P. Kamerling, R. Boelens

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