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.
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 , 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 .
If you’re not watching recent work in biology, you might have thought that light microscopy hit its limits years ago. After all, it’s been around a long time. But to the contrary, microscopic imaging technology just keeps getting better and better. Here you can look with unprecedented clarity at just one of the many dynamic processes going on within a living cell. Specifically, this video shows actin fibers (orange-red), which are key components of the cell’s cytoskeleton, slowly pulling clathrin-coated pits (green), which are basket-like structures containing molecular cargo, away from the cell’s external membrane and deeper within the cell.
This remarkable live-action view was produced using one of two new forms of extended-resolution, structured illumination microscopy (SIM). SIM is faster than other forms of super-resolution fluorescence microscopy. It’s also less damaging to cells, making it the go-to method for live-cell imaging. The downside has been SIM’s limited resolution—just twice that of conventional light microscopes. However, Nobel Prize-winner Eric Betzig and postdoc Dong Li of Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, VA, along with colleagues including Jordan Beach and John Hammer at NIH’s National Heart, Lung, and Blood Institute, recently came up with two different solutions to enhance SIM’s spatial resolution.
Growing up amid the potato and corn fields of western New York state, Jordan Myers got a firsthand look at what it was like to work as a farmer, a homebuilder, even a chimney sweep. But it was television—specifically, “Bill Nye the Science Guy” and “The Magic School Bus”—that introduced him to what would become his future career: science.
Propelled by his curiosity about how living things work, Myers left his hometown of Savannah to attend New York’s Rochester Institute of Technology, where he earned an undergraduate degree in biotechnology, and then headed off to pursue advanced degrees in cell biology at Yale School of Medicine, New Haven, CT. There, as you’ll see in this LabTV profile, he’s trying to develop light microscopy techniques [1,2] to view the cell’s nuclear envelope at nanometer (nm) resolution—a major challenge when one considers that a red blood cell measures about 7,000 nm in diameter.
Other than wondering what might be lurking in those leftovers stashed in the back of the fridge, you probably don’t think much about bacteria. But Robert Morton III—a Ph.D. candidate at Indiana University, Bloomington, and the focus of our latest LabTV profile—sure does. He’s fascinated by the complicated and even beautiful ways in which bacteria interact with their environments. In fact, scientists can learn a whole lot about biology by studying bacteria and other single-celled organisms.
Working in the NIH-funded lab of Yves Brun, Morton has spent many of his days peering through microscopes into the otherwise invisible world of bacteria. His sights are set on the relatively simple, two-component interactions that enable bacteria to sense and respond to various external factors. Each of these interactions features a histidine kinase sensor partnered with a response regulator. Specifically, Morton has focused much of his research on one particular protein thought to play a role in these interactions—a protein that he calls an “orphan” because no scientist has yet identified its partner or determined quite what it does.