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Nobel Prize

Eric Betzig, Stefan Hell, And W. E. Moerner Win 2014 Nobel Prize In Chemistry

Awards: Superresolution fluorescence microscopy has made it possible to capture nanoscale images of cells

by Celia Henry Arnaud
October 8, 2014

Betzig
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Credit:
Matt Stanley/HHMI
20141008lnp1-betzig.jpg
Credit:
Matt Stanley/HHMI
 
Hell
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Credit: Max Planck Institute for Biophysical Chemistry
20141008lnp1-hell.jpg
Credit: Max Planck Institute for Biophysical Chemistry
Moerner
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Credit:
L.A. Cicero
20141008lnp1-moerner.jpg
Credit:
L.A. Cicero

The 2014 Nobel Prize in Chemistry honors three individuals for the development of superresolution fluorescence microscopy, which has made it possible to obtain optical images at the nanometer scale—well below the diffraction limit.

Eric Betzig, 54, of the Howard Hughes Medical Institute’s Janelia Farm campus in Ashburn, Va.; Stefan W. Hell, 51, of the Max Planck Institute for Biophysical Chemistry, in Göttingen, and the German Cancer Research Center, in Heidelberg, Germany; and William E. (W. E.) Moerner, 61, of Stanford University will share the $1.1 million prize.

Moerner was the first person to detect a single fluorescent molecule, which he achieved while working at IBM’s Almaden Research Center in San Jose, Calif. Before that, researchers could only detect many molecules simultaneously.

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Credit: G. Donnert & S. W. Hell/Max Planck Institute for Biophysical Chemistry
The filament structures within a nerve cell are clearly resolved in a STED microscopy image (circular inset) but blurry in a conventional light microscope image.
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Credit: G. Donnert & S. W. Hell/Max Planck Institute for Biophysical Chemistry
The filament structures within a nerve cell are clearly resolved in a STED microscopy image (circular inset) but blurry in a conventional light microscope image.

Moerner later discovered, while working at the University of California, San Diego, that one variant of green fluorescent protein could be turned on and off on command. The protein would fluoresce when excited with 488-nm light, but once it faded the protein wouldn’t turn back on. But Moerner discovered that exposure to 405-nm light reactivated the protein. It could again be excited with 488-nm light.

Such photoswitchable fluorescent proteins form the basis of photoactivated localization microscopy (PALM), which Betzig co-invented with Harald Hess in 2006. They built the original instrument in Hess’s living room.

In PALM, photoactivatable fluorescent proteins are toggled on and off a few at a time. The method requires that the activated proteins be far enough apart that their locations can be precisely determined. An image can be built by repeating the cycle many times and superimposing the images. Similar methods were also developed in 2006 by Xiaowei Zhuang of Harvard University (stochastic optical reconstruction microscopy, or STORM) and by Samuel T. Hess of the University of Maine (fluorescence PALM, or fPALM).

The method developed by Hell—stimulated emission depletion (STED) microscopy—works differently. In that method, one laser beam stimulates fluorescence in labeled biomolecules. A second overlapping doughnut-shaped laser beam turns off that fluorescence in all but a nanometer-sized volume. By scanning across a sample, it is possible to build an image with nanometer-scale resolution.

These original superresolution fluorescence spectroscopy methods improved lateral resolution but they did little to improve depth resolution. Since the introduction of PALM, STORM, STED, and fPALM, the inventors and others have further developed them to acquire three-dimensional images.

Despite its short history, superresolution spectroscopy is already advancing biology. For example, Hell has used STED to look at living nerve cells. Moerner recently used superresolution microscopy to image live bacterial cells in three dimensions. And there’s plenty more to come.

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Credit: HHMI
Betzig and Harald Hess built their original instrument in Hess’s living room.

“I see this as a confluence of areas of science,” American Chemical Society President Thomas J. Barton says. “There’s no question it’s chemistry. But in microscopy, the role of physics is always there. And the uses right now are predominantly in biological molecules. We see a lot of sciences playing a role in the whole picture. I think that’s a very healthy thing.”

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Comments
dr munawar hasan (October 8, 2014 1:34 PM)
Super coverage on super resolution microscopy
Somnath Bhagat (October 8, 2014 11:19 PM)
We are appreciate from your research in microscopy.
CHHANDA CHARAN DANTA (October 8, 2014 11:35 PM)
All right but still it is confused to be in Chemistry ! It goes strongly towards Physics.
niraj sharma (October 9, 2014 5:14 AM)
big discovery
John Carpenter (October 16, 2014 2:29 PM)
Why did the Nobel Committee not include Harald Hess as a co-winner?
satish koppireddi (October 17, 2014 9:48 AM)
It is a great inspiration for young researchers, I congratulate them, I fell very proud as chemistry graduate & doctorate
Leslie Ajayi (October 19, 2014 7:50 PM)
Congratulationans for the inspiration provided by the new Nobel laureates. They are the makers of civilization !
Godwin O. Mbagwu, Sr. (November 1, 2014 10:44 PM)
I see this accomplishment as an excellent model of innovative and collaborative integration of science, technology, engineering, and math (STEM)!
Sunil H Ganatra (November 3, 2014 1:07 AM)
Great Research and I congratulate Dr. Eric Betzig, Dr. Stefan W. Hell, and Dr. William E. (W. E.) Moerner. We learn a lot from you all.

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