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MicroED: From Powder to Structure in a Half-Hour

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MicroED determines structure in 30 min

Credit: Adapted from Jones et al. ChemRxiv.org

Over the past few years, there’s been a great deal of excitement about the power of cryo-electron microscopy (cryo-EM) for mapping the structures of large biological molecules like proteins and nucleic acids. Now comes word of another absolutely incredible use of cryo-EM: determining with great ease and exquisite precision the structure of the smaller organic chemical compounds, or “small molecules,” that play such key roles in biological exploration and drug development.

The new advance involves a cryo-EM technique called microcrystal-electron diffraction (MicroED). As detailed in a preprint on ChemRxiv.org [1] and the journal Angewandte Chemie [2], MicroED has enabled researchers to take the powdered form of commercially available small molecules and generate high-resolution data on their chemical structures in less than a half-hour—dramatically faster than with traditional methods!


A Ray of Molecular Beauty from Cryo-EM

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Rhodopsin

Credit: Subramaniam Lab, National Cancer Institute, NIH

Walk into a dark room, and it takes a minute to make out the objects, from the wallet on the table to the sleeping dog on the floor. But after a few seconds, our eyes are able to adjust and see in the near-dark, thanks to a protein called rhodopsin found at the surface of certain specialized cells in the retina, the thin, vision-initiating tissue that lines the back of the eye.

This illustration shows light-activating rhodopsin (orange). The light photons cause the activated form of rhodopsin to bind to its protein partner, transducin, made up of three subunits (green, yellow, and purple). The binding amplifies the visual signal, which then streams onward through the optic nerve for further processing in the brain—and the ability to avoid tripping over the dog.


Putting Bone Metastasis in the Spotlight

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When cancers spread, or metastasize, from one part of the body to another, bone is a frequent and potentially devastating destination. Now, as you can see in this video, an NIH-funded research team has developed a new system that hopefully will provide us with a better understanding of what goes on when cancer cells invade bone.

In this 3D cross-section, you see the nuclei (green) and cytoplasm (red) of human prostate cancer cells growing inside a bioengineered construct of mouse bone (blue-green) that’s been placed in a mouse. The new system features an imaging window positioned next to the new bone, which enabled the researchers to produce the first series of direct, real-time micrographs of cancer cells eroding the interior of bone.


3D Action Film Stars Cancer Cell as the Villain

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For centuries, microscopes have brought to light the otherwise invisible world of the cell. But microscopes don’t typically visualize the dynamic world of the cell within a living system.

For various technical reasons, researchers have typically had to displace cells, fix them in position, mount them onto slides, and look through a microscope’s viewfinder to see the cells. It can be a little like trying to study life in the ocean by observing a fish cooped up in an 8-gallon tank.

Now, a team partially funded by NIH has developed a new hybrid imaging technology to produce amazing, live-action 3D movies of living cells in their more natural state. In this video, you’re looking at a human breast cancer cell (green) making its way through a blood vessel (purple) of a young zebrafish.

At first, the cancer cell rolls along rather freely. As the cell adheres more tightly to the blood vessel wall, that rolling motion slows to a crawl. Ultimately, the cancer cell finds a place to begin making its way across and through the blood vessel wall, where it can invade other tissues.


A Bacterium Reaches Out and Grabs Some New DNA

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Credit: Dalia Lab, Indiana University, Bloomington

If you like comic book heroes, you’ll love this action-packed video of a microbe with a superpower reminiscent of a miniature Spiderman. Here, for the first time ever, scientists have captured in real-time—and in very cool detail—the important mechanism of horizontal gene transfer in bacteria.

Specifically, you see Vibrio cholerae, the water-dwelling bacterium that causes cholera, stretching out a hair-like appendage called a pilus (green) to snag a free snippet of DNA (red). After grabbing the DNA, V. cholerae swiftly retracts the pilus, threading the DNA fragment through a pore on the cell surface for stitching into its genome.


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