Cell biologists would love to shrink themselves down and actually see, touch and hear the inner workings of cells. Because that's impossible, they have developed an ever-growing collection of microscopes to study cellular innards from the outside. Using these powerful tools, researchers can exhaustively inventory the molecular bits and pieces that make up cells, eavesdrop on cellular communication and spy on cells as they adapt to changing environments. In recent years, scientists have developed new cellular imaging techniques that allow them to visualize samples in ways and at levels of detail never before possible. Many of these techniques build upon the power of electron microscopy (EM) to see ever smaller details. Unlike traditional light microscopy, EM uses electrons, not light, to create an image. To do so, EM accelerates electrons in a vacuum, shoots them out of an electron gun and focuses them with doughnut-shaped magnets onto a sample. When electrons bombard the sample, some pass though without being absorbed while others are scattered. The transmitted electrons land on a detector and produce an image, just as light strikes a detector (or film) in a camera to create a photograph. Transmission electron microscopes can magnify objects more than 10 million times, enabling scientists to see the outline and some details of cells, viruses and even some large molecules. A relatively new form of transmission electron microscopy called cryo-EM enables scientists to view specimens in their natural or near-natural state without the need for dyes or stains. In cryo-EM—the prefix cry- means “cold” or “freezing”—scientists freeze a biological sample so rapidly that water molecules do not have time to form ice crystals, which could shove cellular materials out of their normal place. Cold samples are more stable and can be imaged many times over, allowing researchers to iteratively refine the image, remove artifacts and produce even sharper images than ever before.

When I Grow Up… Gautam Dantas remembers the day in 10^th grade when he first wanted to be a scientist. It was the day he had a new biology teacher, a visiting researcher from the U.S. The teacher passionately described his own biochemical studies of how organisms live together in communities. By the end of the class, Dantas had resolved to earn a Ph.D. in biochemistry. He ended up doing much more—gaining expertise in computational biology, protein design and synthetic biology. He now combines his skills and knowledge in multifaceted research that spans four departments at Washington University in St. Louis. His goal: to better understand and help combat a vital public health threat—drug-resistant bacteria. “Our motivation is that we are living in the antibiotic era, and antibiotic resistance is getting out of control,” Dantas says. “We have very few new antibiotics we can use, so we’re kind of scrambling [to find new ways to treat bacterial diseases].” His research focuses on one of the groups most vulnerable to bacterial infections—newborn babies. According to his lab’s website , the research is “at the interface of microbial genomics, ecology, synthetic biology, and systems biology,” and it aims “to understand, harness, and engineer the biochemical processing potential of microbial communities.” They do it by scrounging around in infant diapers. Antibiotic Angst Since their introduction in the 1940s, antibiotic drugs have saved countless lives. Simultaneously, they weeded out strains of bacteria easily killed by the drugs, allowing drug-resistant strains to thrive. Every year, at least 2 million people in the U.S. become infected and at least 23,000 die from drug-resistant bacteria, according to the Center for Disease Control and Prevention.

Science is beautiful.

For several years, we’ve used this blog to highlight pictures we think are cool, scientifically relevant and visually striking. The images were created by NIGMS-funded researchers in the process of doing their research. Many come from our Life: Magnified collection, which features dozens of stunning photos of life, close-up. We’ll continue to bring you interesting images and information here on Biomedical Beat, but if you can’t get enough of them, we have a new way to share our visual content with you: Instagram.

We’re pleased to announce the launch of our NIGMS Instagram account. We’ll highlight gorgeous images, and bring you the science behind them—straight from our mobile device to yours. Instagram lets us label our images with subject-specific hashtags. You can find our pictures by going on Instagram and searching for #NIGMS. If you’re already an Instagram user, you can follow us @NIGMS_NIH. You can even see our page using a web browser at https://www.instagram.com/nigms_nih/. Let us know what you think!

Also, if you have any stunning images or videos that relate to scientific areas supported by NIGMS, please send them to us. They might end up on our Instagram feed!

What looks like the gossamer wings of a butterfly is actually the retina of a mouse, delicately snipped to lay flat and sparkling with fluorescent molecules. Researchers captured this image while investigating the promise of gene therapy for glaucoma, a progressive eye disease. It all happened at the National Center for Microscopy and Imaging Research (NCMIR) at the University of California, San Diego.

Glaucoma is the leading cause of irreversible blindness. It is characterized by the slow, steady death of certain nerve cells in the retina. If scientists can prevent the death of these cells, which are called retinal ganglion cells, it might be possible to slow the progression of glaucoma. Some researchers are examining the possibility of using gene therapy to do just that.

A major challenge of gene therapy is finding a way to get therapeutic genes into the right cells without damaging the cells in any way. Scientists have had success using a non-disease-causing virus (adeno-associated serotype 2) for this task.

Scientists have identified a new family of proteins that, like the targets of penicillin, help bacteria build their cell walls. The finding might reveal a new strategy for treating a range of bacterial diseases. The protein family is nicknamed SEDS, because its members help control the shape, elongation, division and spore formation of bacterial cells. Now researchers have proof that SEDS proteins also play a role in constructing cell walls. This image shows the movement of a molecular machine that contains a SEDS protein as it constructs hoops of bacterial cell wall material. Any molecule involved in building or maintaining cell walls is of immediate interest as a possible target for antibiotic drugs. That’s because animals, including humans, don’t have cell walls—we have cell membranes instead. So disabling cell walls, which bacteria need to survive, is a good way to kill bacteria without harming patients. This strategy has worked for the first antibiotic drug, penicillin (and its many derivatives), for some 75 years. Now, many strains of bacteria have evolved to resist penicillins—and other antibiotics—making the drugs less effective. According to the Centers for Disease Control and Prevention, drug-resistant strains of bacteria infect at least 2 million people, killing more than 20,000 of them in the U.S. every year. Identifying potential new drug targets, like SEDS proteins, is part of a multi-faceted approach to combating drug-resistant bacteria.

In part II of this series, we reveal how the ECM helps body cells move around, a process vital for wounds to heal and a fetus to grow. Here we introduce the extracellular matrix (ECM) and discuss how it makes our tissues stiff or squishy, solid or see-through.

When we think about how our bodies are made and what they do, we usually focus on organs, tissues and cells. These structures have well-known roles. But around, within and between them is a less understood material that also plays an essential part in making us what we are.

This gelatinous filler material is known as the extracellular matrix (ECM). Once thought to be the biological equivalent of bubble wrap, we now know that the ECM is a dynamic, physiologically active component of all our tissues. It guides cell shape, orientation and function.

The ECM is found in all of our body parts. In some tissues, it’s a thin layer separating cells, like mortar between bricks. In other tissues, it’s the major constituent.

The ECM is most prevalent in connective tissue, the material that forms our skeletons, cushions our internal organs and winds between blood vessels and around nerves. In connective tissue, the ECM is more abundant than the cells suspended within it.

What makes the ECM truly unique is its variability: Its texture, composition and functions vary by body part. That’s because the ECM’s deceptively simple recipe of water, fibrous proteins and carbohydrates has virtually endless variations.

In general, the fibrous proteins give the ECM its texture and help cells adhere properly. Carbohydrates in the ECM absorb water and swell to form a gel that acts as an excellent shock absorber.

If you’ve ever felt a slimy coating on your teeth, scrubbed grime from around a sink drain or noticed something growing between the tiles of a shower, you’ve encountered a biofilm. Made up of communities of bacteria and other microorganisms, biofilms thrive where they can remain moist and relatively undisturbed. As they enlarge, biofilms can block narrow passages like medical stents, airways, pipes or intestines.

Maria Diuk-Wasser grew up on the 10^th floor of an apartment building in the middle of a bustling city. With no forests or meadows nearby, she read book after book about the natural world and surrounded herself with houseplants. “I yearned for nature,” Diuk-Wasser says. “But my parents couldn’t provide it. They’re city people. They didn’t know anything about hiking or camping.” These days, Diuk-Wasser still spends a lot of time in a city—she’s a professor at Columbia University in New York, the most populous city in the U.S.—but she also gets plenty of time in the woods. She hikes for hours through coastal New England forests, some of the loveliest in the country, searching for what many consider less-than-lovely inhabitants: mice and ticks.

Invasive fungal infections—the kind that infect the bloodstream, lung and brain—are inordinately deadly. A big part of the problem is the lack of drugs that are both effective against the fungi and nontoxic to humans. The situation might change in the future though, thanks to the work of a multidisciplinary research team led by chemist Martin Burke at the University of Illinois. For years, the team has focused on an antifungal agent called amphotericin B (AmB for short). Although impressively lethal to fungi, AmB is also notoriously toxic to human cells. Most recently, the research team chemically modified the drug to create compounds that kill fungi, but don’t disrupt human cells. The scientists explain it all in the latest issue of Nature Chemical Biology. Invasive fungal infections are so intractable because most antifungal drugs aren’t completely effective. Plus, fungi have a tendency to develop resistance to them. AmB is a notable exception. Isolated 50 years ago from Venezuelan dirt, AmB has evaded resistance and remains highly effective. Unfortunately, it causes side effects so debilitating that some doctors call it “ampho-terrible.” At high doses, it is fatal. For decades, scientists believed that AmB molecules kill fungal cells by forming membrane-piercing pores, or ion channels, through which the cells’ innards leak out. Last year, Burke’s group overturned this well-established concept using evidence from nuclear magnetic resonance, chemistry and cell-based experiments. The researchers showed that AmB molecules assemble outside cells into lattice-like structures. These structures act as powerful sponges, sucking vital lipid molecules, called ergosterol, right out of the fungal cell membrane, destroying the cell.

“I really look at my job as an adventure,” says Nels Elde. “The ability to follow your nose through different fields is what motivates me.” Elde has used that approach to weave evolutionary genetics, bacteriology, virology, genomics and cell biology into his work. While a graduate student at the University of Chicago and postdoctoral researcher at the Fred Hutchinson Cancer Research Center in Seattle, he became interested in how interactions between pathogens (like viruses and bacteria) and their hosts (like humans) drive the evolution of both parties. He now works in Salt Lake City, where, as an avid outdoorsman, he draws inspiration from the wild landscape. Outside the lab, Elde keeps diverse interests and colorful company. His best friend wrote a song about his choice of career as a cell biologist. (You can hear this song at the end of the 5-minute video in which Elde explains his work.)