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

SequencingSanger, 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 proteinUvrC 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