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3D imaging

Got It Down Cold: Cryo-Electron Microscopy Named Method of the Year

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Caption: Composite image of beta-galactosidase showing how cryo-EM’s resolution has improved dramatically in recent years. Older images to the left, more recent to the right.
Credit: Veronica Falconieri, Subramaniam Lab, National Cancer Institute

In the quest to find faster, better ways of mapping the structure of proteins and other key biological molecules, a growing number of researchers are turning to an innovative method that pushes the idea of a freeze frame to a whole new level:  cryo-electron microscopy (cryo-EM). The technique, which involves flash-freezing molecules in liquid nitrogen and bombarding them with electrons to capture their images with a special camera, has advanced dramatically since its inception thanks to the efforts of many creative minds. In fact, cryo-EM has improved so much that its mapping performance now rivals that of X-ray crystallography [1], the long-time workhorse of drug developers and structural biologists.

To get an idea of just how far cryo-EM has come over the last decade, take a look at the composite image above, which shows a bacterial enzyme (beta-galactosidase) bound to a drug-like molecule (phenylethyl beta-D-thiogalactopyranoside). To the left, you see a blob-like area generated by cryo-EM methods that would have been considered state-of-the-art just a few years ago. To the right, there’s an exquisitely detailed structure, which was produced at more than 10-times greater resolution using the latest advances in cryo-EM. In fact, today’s cryo-EM is so powerful that researchers can almost make out individual atoms! Very impressive, and just one of the many reasons why the journal Nature Methods recently named cryo-EM its “Method of the Year” for 2015 [2].

Snapshots of Life: Allergen Art

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Pollen grains

Credit: Edna, Gil, and Amit Cukierman, Fox Chase Cancer Center, Philadelphia

Seasonal allergy sufferers, allow me to take advantage of the powers of confocal microscopy to introduce you to your tormenter: pollen. Although pollen grains look amazing at this magnification, their effects on many of us are not so wonderful. These spiky spheres can trigger an immune reaction that produces the runny nose, itchy eyes, and other symptoms that make people with pollen allergies miserable from early spring through late fall.

In fact, this image was created by a seasonal allergy sufferer who also happens to be a cell biologist. On a Saturday afternoon about a decade ago, Edna Cukierman of Philadelphia’s Fox Chase Cancer Center had just received a new spinning disc confocal microscope and couldn’t wait to try it out. There was just one catch—she also had to watch her two children. Not to be deterred, this multi-tasking scientist/mom turned the process of calibrating her new microscope into a creative way of entertaining her kids.

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