Tag: Cellular Imaging

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Freezing a Moment in Time: Snapshots of Cryo-EM Research

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To get a look at cell components that are too small to see with a normal light microscope, scientists often use cryo-electron microscopy (cryo-EM). As the prefix cryo- means “cold” or “freezing,” cryo-EM involves rapidly freezing a cell, virus, molecular complex, or other structure to prevent water molecules from forming crystals. This preserves the sample in its natural state and keeps it still so that it can be imaged with an electron microscope, which uses beams of electrons instead of light. Some electrons are scattered by the sample, while others pass through it and through magnetic lenses to land on a detector and form an image.

Typically, samples contain many copies of the object a scientist wants to study, frozen in a range of orientations. Researchers take images of these various positions and combine them into a detailed 3D model of the structure. Electron microscopes allow us to see much smaller structures than light microscopes do because the wavelengths of electrons are much shorter than the wavelength of light. NIGMS-funded researchers are using cryo-EM to investigate a range of scientific questions.

Caught in Translation

One cluster that is yellow, purple, and orange and another that is beige, purple, and green. 3D reconstructions of two stages in the assembly of the bacterial ribosome created from time-resolved cryo-EM images. Credit: Joachim Frank, Columbia University.

Joachim Frank, Ph.D., a professor of biochemistry and molecular biophysics and of biological sciences at Columbia University in New York, New York, along with two other researchers, won the 2017 Nobel Prize in Chemistry for developing cryo.

Dr. Frank’s lab focuses on the process of translation, where structures called ribosomes turn genetic instructions into proteins, which are needed for many chemical reactions that support life. Recently, Dr. Frank has adopted and further developed a technique called time-resolved cryo-EM. This method captures images of short-lived states in translation that disappear too quickly (after less than a second) for standard cryo-EM to capture. The ability to fully visualize translation could help researchers identify errors in the process that lead to disease and also to develop treatments.

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Cool Images: A Colorful—and Halloween-Inspired—Collection

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Transformations aren’t just for people or pets around Halloween. Scientific images also can look different than you might expect, depending on how they’re photographed. Check out these tricky-looking images and learn more about the science behind them.

A human fibroblast cell dividing. A tan-colored area surrounds the cell that contains two magenta-colored centers. Green dots line the area where the cell is dividing. Credit: Nilay Taneja, Vanderbilt University, and Dylan T. Burnette, Ph.D., Vanderbilt University School of Medicine.

Do you have a hunch about what this image is? Perhaps something to do with dry leaves? It’s a human fibroblast cell undergoing cell division, or cytokinesis, into two daughter cells. Cytokinesis is essential for the growth and development of new cells. And fibroblasts play a big role in wound healing by helping with contraction and closure.

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Molecular Fireworks: How Microtubules Form Inside Cells

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A video depicting red strands of various lengths exploding outward from a focal point at the left. The strands are tipped in neon green.
       Microtubules sprout from one another. Credit: Petry lab, Princeton University.

The red spray pictured here may look like fireworks erupting across the night sky on July 4th, but it’s actually a rare glimpse of tiny protein strands called microtubules sprouting and growing from one another in a lab. Microtubules are the largest of the molecules that form a cell’s skeleton. When a cell divides, microtubules help ensure that each daughter cell has a complete set of genetic information from the parent. They also help organize the cell’s interior and even act as miniature highways for certain proteins to travel along.

As their name suggests, microtubules are hollow tubes made of building blocks called tubulins. Scientists know that a protein called XMAP215 adds tubulin proteins to the ends of microtubules to make them grow, but until recently, the way that a new microtubule starts forming remained a mystery.

Sabine Petry Link to external web site and her colleagues at Princeton University developed a new imaging method for watching microtubules as they develop and found an important clue to the mystery. They adapted a technique called total internal reflection fluorescence (TIRF) microscopy, which lit up only a tiny sliver of a sample from frog egg (Xenopus) tissue. This allowed the scientists to focus clearly on a few of the thousands of microtubules in a normal cell. They could then see what happened when they added certain proteins to the sample.

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Cellular Footprints: Tracing How Cells Move

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An engineered cell (green) in a fruit fly follicle (red), or egg case, leaves a trail of fluorescent material as it moves across a fruit fly egg chamber, allowing scientists to trace its path and measure how long it took to complete its journey. Credit: David Bilder, University of California, Berkeley.

Cells are the basis of the living world. Our cells make up the tissues and organs of our bodies. Bacteria are also cells, living sometimes alone and sometimes in groups called biofilms. We think of cells mostly as staying in one spot, quietly doing their work. But in many situations, cells move, often very quickly. For example, when you get a cut, infection-fighting cells rally to the site, ready to gobble up bacterial intruders. Then, platelet cells along with proteins from blood gather and form a clot to stop any bleeding. And finally, skin cells surrounding the wound lay down scaffolding before gliding across the cut to close the wound.

This remarkable organization and timing is evident right from the start. Cells migrate within the embryo as it develops so that body tissues and organs end up in the right places. Harmful cells use movement as well, as when cells move and spread (metastasize) from an original cancer tumor to other parts of the body. Learning how and why cells move could give scientists new ways to guide those cells or turn off or slow down the movement when needed.

Glowing Breadcrumbs

Scientists studying how humans and animals form, from a single cell at conception to a complex body at birth, are particularly interested in how and when cells move. They use research organisms like the fruit fly, Drosophila, to watch movements by small populations of cells. Still, watching cells migrate inside a living fly is challenging because the tissue is too dense to see individual cell movement. But moving those cells to a dish in the lab might cause them to behave differently than they do inside the fly. To solve this problem, NIGMS-funded researcher David BilderLink to external web site and colleagues at the University of California, Berkeley, came up with a way to alter fly cells so they could track how the cells behave without removing them from the fly. They engineered the cells to lay down a glowing track of proteins behind them as they moved, leaving a traceable path through the fly’s tissue. The technique, called M-TRAIL (matrix-labeling technique for real-time and inferred location), allows the researchers to see where a cell travels and how long it takes to get there.

Bilder and his team first used M-TRAIL in flies to confirm the results of past studies of Drosophila ovaries in the lab using other imaging techniques. In addition, they found that M-TRAIL could be used to study a variety of cell types. The new technique also could allow a cell’s movement to be tracked over a longer period than other imaging techniques, which become toxic to cells in just a few hours. This is important, because cells often migrate for days to reach their final destinations.

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Chasing Fireflies—and Better Cellular Imaging Techniques

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A glowing firefly sitting in a person's open palm. Firefly. Credit: Stock photo.

The yellow-green glow from this summer’s fireflies teased my kids across the yard. Max and Stella zigzagged the grass, occasionally jumping into the air to cup a firefly in their hands and then proudly shouting, “I got one!”

Chasing fireflies on a summer night is a childhood rite of passage for many, including Nathan Shaner who grew up in New Jersey. “It was one of my favorite things about summer,” he recalls. “I’d catch them with my hands—I’d never jar them.”

Today, Shaner studies the science of bioluminescence, which gives fireflies and many other organisms the natural ability to emit light. His goal is to make bright bioluminescent tags that he and other scientists can use to study living cells in greater detail. “There’s this very beautiful thing that evolved in nature, and we can use it to enable new discoveries,” he says.

Thousands of organisms glow as a way to communicate, spook predators, lure prey or attract mates. There are a few terrestrial examples, such as fireflies, glowworm insect larvae and foxfire fungi, and many more aquatic ones, including types of marine plankton, fish, jellyfish, shrimp, squid and sea urchins. One research team estimated nearly three quarters of sea life have bioluminescent capabilities.

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Beauty is in the Eye

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Our eyes are the gateway to countless brilliant sights. However, as evidenced by the images on this page, the eye itself can be breathtakingly exquisite as well. This May, as we celebrate Healthy Vision Month with the National Eye Institute, we hope sharing the beauty hidden in your eyes will inspire you to take the necessary steps to protect your vision, prevent vision loss and make the most of the vision you have remaining.

Visit NEI to learn more about caring for your eyes.

Happy Healthy Vision Month!

Mammalian eye

Eyes are beautiful, and they take on a whole new look in this agate-like image, which highlights just how complex mammalian eyes really are. Researchers used staining and imaging techniques to turn each of the 70-plus cell types in this mouse eye a different color. The image won first place in the 2011 International Science and Engineering Visualization Challenge. Credit: Bryan William Jones, University of Utah Moran Eye Center.
Mouse eye

This burst of starry points is actually part of the retina from a mouse eye. The image comes from a research project investigating the promise of gene therapy for glaucoma. Untreated glaucoma is a leading cause of blindness. The disease is characterized by the death of cells called retinal ganglion cells. Scientists are hoping to deliver gene therapy to these cells as a treatment for glaucoma. In this photo, a fluorescent protein (GFP) lights up to show the location of retinal ganglion cells—and to reveal how well the proposed gene therapy technique might work. Credit: Kenyoung Kim, Wonkyu Ju and Mark Ellisman, National Center for Microscopy and Imaging Research, University of California, San Diego.
Mouse eye

What appears as a tree branch painstakingly wrapped in green wire is a microscopic blood vessel from the retina at the back of a mouse eye. These vessels can help diagnose conditions such as glaucoma and diabetic eye disease. The vessels also have a characteristic appearance in people with high blood pressure. This detailed image was created to help scientists understand what happens in a genetic disease called neurofibromatosis, in which tumors begin to form on nerve tissue. Credit: National Center for Microscopy and Imaging Research, University of California, San Diego.
Mouse eye

Like a colorful fiber-optic network, this microscopic layer from a mouse’s eye relays information from the retina to the brain. Retinal ganglion neurons (orange) and their associated optic nerve fibers (red) are overlaid with blood vessels (blue) and spidery glial cells (green). By comparing detailed images of healthy eye tissues with similar images of a diseased eye, researchers can learn about changes in biology that occur as eye diseases develop. Credit: National Center for Microscopy and Imaging Research, University of California, San Diego.
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Actin’s Many Roles

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Skin cancer cells

Skin cancer cells from a mouse. Credit: Catherine and James Galbraith, Oregon Health and Science University, Center for Spatial Systems Biomedicine, Knight Cancer Institute.

This heart-shaped image shows two mouse skin cancer cells connected to each other with actin, a protein that is part of the cellular skeleton. Researchers use mouse cells like these to tease out the molecular methods that cancer uses to invade new tissues in the body. It turns out that actin plays an essential role.

Cells can move as a collective, or independently. Movement of an individual cell requires a series of carefully controlled steps. Among them, a cell must break contacts with its neighbor cells and change its connections to the proteins and fibers around it. In addition, it must sense and follow a chemical path through the tissue it lies in. To do this, a cell changes shape, molding its membrane into flaps or feet called protrusions reaching in the direction it is traveling. Actin, among a variety of other molecules, is involved in all of these steps, but especially the shape change, when it gathers inside the cell membrane to help form the protrusions. Continue reading “Actin’s Many Roles”

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Metals in Medicine

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An exhibit called “Minerals in Medicine” opened at the NIH Clinical Center last month (see slideshow). The display features a fascinating overview of how dozens of minerals are used to create drugs and medical instruments useful in treating disease and maintaining health. The minerals ranged from commonplace ones like quartz, which is used to make medical instruments, to more exotic ones like hubnerite, a source of the metal tungsten, which is used in radiation shielding.

Inspired by this collection, which is co-sponsored by NIH and the Smithsonian Institution, we highlight here examples of “Metals in Medicine.”

Copper and Fat Metabolism

Fluorescent imaging of copper in white fat cells from mice.

Fluorescent imaging of copper in white fat cells from mice. The left panel shows fat cells with normal levels of copper, and the right panel shows fat cells deficient in copper. Credit: Lakshmi Krishnamoorthy and Joseph Cotruvo Jr., University of California, Berkeley.

What does a metal like copper have to do with our ability to breakdown fat? Researchers explored this question by observing mice with Wilson’s disease—a rare, inherited condition that causes copper to accumulate in the liver, brain and other vital organs. The mice with the condition usually have larger deposits of fat compared to healthy mice. To confirm that fat metabolism is somehow compromised in these mice, the researchers treated them with a drug that induces the breakdown of fat. And indeed they found that less fat was metabolized in mice with the disease.

In an effort to investigate what role copper may be playing in fat metabolism, the researchers examined adipose tissue, or fat, cells under a microscope to track the metal’s interactions with various proteins in the cell. They discovered that copper inhibits an enzyme called PDE3. This enzyme usually prevents another enzyme called cAMP from helping to break down fat. The researchers concluded that copper actually promotes fat metabolism. This work shows that transition metal nutrients can play signaling roles, which has been previously thought to be restricted to alkali and alkaline earth metals like sodium, potassium and calcium.

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NIGMS Is on Instagram!

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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/ Exit icon. 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!

See those finger-like projections? They are called villi. This image shows the small intestine, where most of the nutrients from the food we eat are absorbed into the bloodstream. The villi increase the organ’s surface area, making nutrient absorption more efficient. Credit: National Center for Microscopy and Imaging Research.
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We need zinc. It’s an essential nutrient for growth and development, fending off invading microbes, healing injuries, and all sorts of cellular processes. We get the mineral through our diet, but people in certain parts of the world don’t get enough. Researchers study how plants acquire and process zinc, hoping to find ways to increase the nutrient in food crops. Using synchrotron X-ray fluorescence technology, scientists created this heat map of zinc in a leaf from a plant called Arabidopsis thaliana (zinc levels from lowest to highest: blue, green, red, white). Credit: Suzana Car and Mary Lou Guerinot, Dartmouth College.
#science Exit icon #biology Exit icon #research Exit icon #botany Exit icon #plant Exit icon #arabidopsis Exit icon #zinc Exit icon #microscopy Exit icon #synchrotron Exit icon #x-ray Exit icon #modelorganism Exit icon #leaf Exit icon #heatmap Exit icon #scienceisbeautiful Exit icon #nigms Exit icon #nih Exit icon

Beautiful brain! This image shows the cerebellum, which is the brain’s locomotion control center. Every time you shoot a basketball, tie your shoe or chop an onion, your cerebellum fires into action. Found at the base of your brain, the cerebellum is a single layer of tissue with deep folds like an accordion. People with damage to this region of the brain often have difficulty with balance, coordination and fine motor skills. Credit: Tom Deerinck and Mark Ellisman, NCMIR
#science Exit icon #biology Exit icon #research Exit icon #cerebellum Exit icon #neuroscience Exit icon #neurobiology Exit icon #brain Exit icon #brains Exit icon #brainimages Exit icon #neuroanatomy Exit icon #microscopy Exit icon #scienceisbeautiful Exit icon #sciart Exit icon #nigms Exit icon #nih Exit icon #NCMIR Exit icon #UCSD Exit icon

Scientists can learn a lot by studying pigment cells, which give animals their colorful skins, eyes, hair and scales. We can even gain insight into skin cancers, like melanoma, that originate from pigment cells. Pigment cells can form all sorts of patterns, like these stripes on the fin of a pearl danio, a type of tropical minnow. Credit: David Parichy, University of Washington.
#biology Exit icon #marinebiology Exit icon #marinescience Exit icon #cell Exit icon #pigmentcell Exit icon #xanthophore Exit icon #science Exit icon #research Exit icon #cellbiology Exit icon #microscopy Exit icon #scienceisbeautiful Exit icon #scienceiscool Exit icon #zebrafish Exit icon #universityofwashington Exit icon
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Lighting Up the Promise of Gene Therapy for Glaucoma

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Retinal ganglion cells in the mouse.

Retinal ganglion cells in the mouse retina that do (bright, yellow spots throughout) and do not (blue streaks, mostly along the edges) contain a specific gene that scientists introduced with a virus. Credit: Kenyoung (“Christine”) Kim, Wonkyu Ju and Mark Ellisman, National Center for Microscopy and Imaging Research, University of California, San Diego.

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 Exit icon (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. Continue reading “Lighting Up the Promise of Gene Therapy for Glaucoma”