FROM THE DISCOVERY OF HELIX
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