They were awarded the prize for developing cryo-electro microscopy.
Scientists Jacques Dubochet, Joachim Frank and Richard Henderson were awarded the Nobel Chemistry Prize today for cryo-electron microscopy, a simpler and better method for imaging tiny, frozen molecules.
Thanks to their team's new "cool method", involving electron beams to photograph bits of cells, "researchers can now routinely produce three-dimensional structures of biomolecules", the Nobel chemistry committee said.
"Researchers can now freeze biomolecules mid-movement and visualise processes they have never previously seen, which is decisive for both the basic understanding of life's chemistry and for the development of pharmaceuticals," the committee added.
This method allows bio-molecules to be kept frozen in their natural state without the need for dyes or fixatives.
It is used study the tiniest details of cell structures, viruses and proteins.
"When researchers began to suspect that the Zika virus was causing the epidemic of brain-damaged newborns in Brazil, they turned to cryo-EM (electron microscopy) to visualise the virus," the committee said.
The prize comes with nine million Swedish kronor (around USD 1.1 million or 943,100 euros).
Know your laureautes
JACQUES DUBOCHET
Born 1942 in Aigle, Switzerland.
Ph.D. 1973, University of Geneva and
University of Basel, Switzerland.
Honorary Professor of Biophysics,
University of Lausanne, Switzerland.
JOACHIM FRANK
Born 1940 in Siegen, Germany. Ph.D.
1970, Technical University of Munich,
Germany. Professor of Biochemistry
and Molecular Biophysics and of Biological
Sciences, Columbia University,
New York, US
RICHARD HENDERSON
Born 1945 in Edinburgh, Scotland.
Ph.D. 1969, Cambridge University, UK.
Programme Leader, MRC Laboratory
of Molecular Biology, Cambridge, UK.
A brief history of imaging
In the first half of the twentieth century, biomolecules – proteins, DNA and RNA – were terrain incognita on the map of biochemistry. Scientists knew they played fundamental roles in the cell, but had no idea what they looked like. It was only in the 1950s, when researchers at Cambridge began to expose protein crystals to X-ray beams, that it was first possible to visualise their wavy and spiralling structures.
In the early 1980s, the use of X-ray crystallography was supplemented with the use of nuclear magnetic resonance (NMR) spectroscopy for studying proteins in solid state and in solution. This
technique not only reveals their structure, but also how they move and interact with other molecules.
Thanks to these two methods, there are now databases containing thousands of models of biomolecules that are used in everything from basic research to pharmaceutical development. However, both methods suffer from fundamental limitations. NMR in solution only works for relatively small proteins.
X-ray crystallography requires that the molecules form well-organised crystals, such as when water freezes to ice. The images are like black and white portraits from early cameras – their rigid pose reveals very little about the protein’s dynamics.
Also, many molecules fail to arrange themselves in crystals, which caused Richard Henderson to abandon X-ray crystallography in the 1970s – and this is where the story of 2017’s Nobel Prize in Chemistry begins.
Henderson unhappy
Richard Henderson received his PhD from the bastion of X-ray crystallography, Cambridge, UK. He used the method for imaging proteins, but setbacks arose when he attempted to crystallise a protein that was naturally embedded in the membrane surrounding the cell.
Henderson produces the first image at atomic resolution Over the following years, electron microscopy gradually improved. The lenses got better and cryotechnology developed in which the samples were cooled with liquid nitrogen during the measurements, protecting them from being damaged by the electron beam.
Richard Henderson gradually added more details to the model of bacteriorhodopsin. To get the sharpest images he travelled to the best electron microscopes in the world. They all had their weaknesses, but complemented each other. Finally, in 1990, 15 years after he had published the first model, Henderson achieved his goal and was able to present a structure of bacteriorhodopsin at atomic resolution.
On the other side of the Atlantic, at the New York State Department of Health, Joachim Frank had long worked to find a solution to just that problem.
In 1975, he presented a theoretical strategy where the apparently minimal information found in the electron microscope’s two-dimensional images
could be merged to generate a high-resolution, three-dimensional whole. It took him over a decade to realise this idea.
Joachim Frank’s image processing method was fundamental to the development of cryo-EM.A few years earlier, Frank was perfecting his computer programs, Jacques Dubochet was recruited to the European Molecular Biology Laboratory in Heidelberg to solve another of the electron microscope’s basic problems: how biological samples dry out and are damaged when exposed to a vacuum.
In 1975, Henderson used a glucose solution to protect his membrane from dehydrating, but this method did not work for water-soluble biomolecules. Other researchers had tried freezing the samples because ice evaporates more slowly than water, but the ice crystals disrupted the electron beams so much that the images were useless.
The vaporising water was a major dilemma. However, Jacques Dubochet saw a potential solution: cooling the water so rapidly that it solidified in
its liquid form to form a glass instead of crystals. A glass appears to be a solid material, but is actually a fluid because it has disordered molecules.
Dubochet realised that if he could get water to form glass – also known as vitrified water – the electron beam would diffract evenly and provide a uniform background
This means now every corner of the molecular structure can be studied. There are a number of benefits that make cryo-EM so revolutionary: Dubochet’s vitrification method is relatively easy to use and requires a minimal sample size. Due to the rapid cooling process, biomolecules can be frozen mid-action and researchers can take image series that capture different parts of a process.
This way, they produce ‘films’ that reveal how proteins move and interact with other molecules. Using cryo-EM, it is also easier than ever before to depict membrane proteins, which often function as targets for pharmaceuticals, and large molecular complexes. However, small proteins cannot be studied
with electron microscopy, but they can be visualised using NMR spectroscopy or X-ray crystallography.
After Joachim Frank presented the strategy for his general image processing method in 1975, a
researcher wrote: “If such methods were to be perfected, then, in the words of one scientist, the sky
would be the limit.”
Now we are there – the sky is the limit. Jacques Dubochet, Joachim Frank and Richard Henderson have, through their research, brought “the greatest benefit to mankind.” Each corner of the cell can be captured in atomic detail and biochemistry is all set for an exciting future.
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}
 "Nobel Chemistry")
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}
)
){kind=small}
){kind=small}
)
)
)
)
)
){kind=small}
){kind=small}
){kind=small}
){kind=small}
){kind=small}