Cool Videos: Fireworks under a Microscope

This Fourth of July, many of you will spread out a blanket and enjoy an evening display of fireworks with their dramatic, colorful bursts. But here’s one pyrotechnic pattern that you’ve probably never seen. In this real-time video, researchers set off some fluorescent fireworks under their microscope lens while making an important basic discovery about how microtubules, the hollow filaments that act as the supportive skeleton of the cell, dynamically assemble during cell division.

The video starts with a few individual microtubule filaments (red) growing linearly at one end (green). Notice the green “comets” that quickly appear, followed by a red trail. Those are new microtubules branching off. This continuous branching is interesting because microtubules were generally thought to grow linearly in animal cells (although branching had been observed a few years earlier in fission yeast and plant cells). The researchers, led by Sabine Petry, now at Princeton University, Princeton, NJ, showed for the first time that not only do new microtubules branch during cell division, but they do so very rapidly, going from a few branches to hundreds in a matter of minutes [1].

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Snapshots of Life: Development in Exquisite Detail

Developmental biology

Credit: Shachi Bhatt and Paul Trainor, Stowers Institute for Medical Research, Kansas City, MO

If you’ve ever tried to take photos of wiggly kids, you know that it usually takes several attempts before you get the perfect shot. It’s often the same for biomedical researchers when taking images with microscopes because there are so many variables—from sample preparation to instrument calibration—to take into account. Still, there are always exceptions where everything comes together just right, and you are looking at one of them! On her first try at using a confocal microscope to image this cross-section of a mouse embryo’s torso, postdoc Shachi Bhatt captured a gem of an image that sheds new light on mammalian development.

Bhatt, who works in the NIH-supported lab of Paul Trainor at the Stowers Institute for Medical Research, Kansas City, MO, produced this micrograph as part of a quest to understand the striking parallels seen between the development of the nervous system and the vascular system in mammals. Fluorescent markers were used to label proteins uniquely expressed in each type of tissue: reddish-orange delineates developing nerve cells; gray highlights developing blood vessels; and yellow shows where the nerve cells and blood vessels overlap.

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A Look Inside a Beating Heart Cell

Caption: Microtubules (blue) in a beating heart muscle cell, or cardiomyocyte. Credit: Lab of Ben Prosser, Ph.D., Perelman School of Medicine, University of Pennsylvania

You might expect that scientists already know everything there is to know about how a healthy heart beats. But researchers have only recently had the tools to observe some of the dynamic inner workings of heart cells as they beat. Now an NIH-funded team has captured video to show that a component of a heart muscle cell called microtubules—long thought to be very rigid—serve an unexpected role as molecular shock absorbers.

As described for the first time recently in the journal Science, the microtubules buckle under the force of each contraction of the muscle cell before springing back to their original length and form. The team also details a biochemical process that allows a cell to fine-tune the level of resistance that the microtubules provide. The findings have important implications for understanding not only the mechanics of a healthy beating heart, but how the abnormal stiffening of heart cells might play a role in various forms of cardiac disease.

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Snapshots of Life: A Kaleidoscope of Worms

C. elegans

Credit: Adam Brown and David Biron, University of Chicago

What might appear to be a view inside an unusual kaleidoscope is actually a laboratory plate full of ravenous roundworms (Caenorhabditis elegans) as seen through a microscope. Tens of thousands of worms (black), each about 1 millimeter in length at adulthood, are grazing on a field of bacteria beneath them. The yellow is a jelly-like growth medium called agar that feeds the bacteria, and the orange along the borders was added to enhance the sunburst effect.

The photo was snapped and stylized by NIH training grantee Adam Brown, a fourth-year Ph.D. student in the lab of David Biron at the University of Chicago. Brown uses C. elegans to study the neurotransmitter serotonin, a popular drug target in people receiving treatment for depression and other psychiatric disorders. This tiny, soil-dwelling worm is a go-to model organism for neuroscientists because of its relative simplicity, short life spans, genetic malleability, and complete cell-fate map. By manipulating the different components of the serotonin-signaling system in C. elegans, Brown and his colleagues hope to better understand the most basic circuitry in the central nervous system that underlies decision making, in this case choosing to feed or forage.

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


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].

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