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Nobel lecture
Early cryo-electron microscopy
Jacques Dubochet
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Thank you
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Sir John Kendrew Edouard Kellenberger
Early cryo-electron microscopy Jacques Dubochet 1 Thank you 2 - - PowerPoint PPT Presentation
Early cryo-electron microscopy Jacques Dubochet 1 Thank you 2 - - PowerPoint PPT Presentation
Nobel lecture Early cryo-electron microscopy Jacques Dubochet 1 Thank you 2 Edouard Kellenberger Sir John Kendrew Why cryo-EM? 3 Aggregation 4 The bad shape of a T4 bacteriophage 5 Negative staining Brenner & Horne, 1959
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Why cryo-EM?
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Aggregation
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The bad shape of a T4 bacteriophage
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Negative staining Brenner & Horne, 1959 Freeze-drying
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Nigel Unwin
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Bob Glaeser
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Taylor, K.A. and R.M. Glaeser, Electron microscopy of frozen hydrated biological specimens.
- J. Ultrastruct. Res., 1976.
55(3): p. 448-56.
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1978 EMBL
(European Molecular Biology Laboratory)
A Project:
How to deal with water in cryo-electron microscopy?
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Ice is not like liquid water
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A Problem
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High Tech
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Ice at EMBL
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High Tech
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Vitreous Water
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The “vitrification” man
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Alasdair McDowall
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This was the first Aha!
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The trouble with vitreous water is that vitrification should be impossible
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Farther Basile Luyet Founder of cryobiology
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Luyet, B. J., & Gehenio, P. M. (1940). Life and death at low
- temperature. Normandy,
Missouri: Biodynamica.
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Savièse
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« You can’t bend Nature »
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Mayer, E. and P. Brüggeller. 1980. "Complete vitrification in pure liquid water and dilute aqueous solutions." Nature 288:569-571. Dubochet, J., & McDowall, A. W. (1981). Vitrification of pure water for electron microscopy. J. Microscopy, 124, RP3-RP4.
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Conclusion I
Vitreous water is not what we thought … … but it works so well for cryo-electron microscopy!
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Conclusion II
What is water ?
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Wait to know more
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The second Aha!
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Marc Adrian † 2013
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Cryo-em of thin vitrified film Semliki Forest Virus
Marc Adrian
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1984
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SFV
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Towards high resolution and 3d reconstruction
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1986
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... then, from blobology to chemistry
Richard Henderson, Joachim Frank
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From 35 to 3.5 Å
Thirty years
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From 35 to 3.5 Å
Thirty years A ten times better resolution
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From 35 to 3.5 Å
Thirty years A ten times better resolution A thousand times more information
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From 35 to 3.5 Å
Thirty years A ten times better resolution A thousand times more information Seeing atoms
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From 35 to 3.5 Å
Thirty years A ten times better resolution A thousand times more information Seeing atoms Chemistry
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Fitzpatrick, A. W. P., Falcon, B., He, S., Murzin, A. G., Murshudov, G., Garringer, H. J., . . . Scheres,
- S. H. W. (2017). Cryo-EM
structures of tau filaments from Alzheimer's disease. Nature, 547(7662), 185-190. doi:10.1038/nature23002.
From Chemistry to Medicine
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The Power of Knowledge
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From Scarcity to Excess
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Science without conscience is but the ruin of the soul!
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François Rabelais 1532
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Coming out of the Ivory tower
A curriculum: Biology and Society To ensure that our students turn out to be as good citizens as they are good biologists
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How can we be as good in using knowledge for the well-being of all as we are in producing it?
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Imagine . . .
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You may say I’m a dreamer But I’m not the only one I hope some day you’ll join us And the world will live as one
John Lennon
Imagine . . .
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Thank-you
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