Tag: Cellular Processes

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Cool Tools: Pushing the Limits of High-Resolution Microscopy

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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.

This image, showing a single protein molecule, is a montage. It was created to demonstrate how dramatically cryo-EM has improved in recent years. In the past, cryo-EM was only able to obtain a blobby approximation of a molecule’s shape, like that shown on the far left. Now, the technique yields exquisitely detailed images in which individual atoms are nearly visible (far right). Color is artificially applied. Credit: Veronica Falconieri, Subramaniam Lab, National Cancer Institute.

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. Continue reading “Cool Tools: Pushing the Limits of High-Resolution Microscopy”

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Interview With a Scientist: Thomas O’Halloran, Metal Maestro

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Inside our bodies is a surprising amount of metal. Not enough to set off the scanners at the airport or make us rich, but enough to fill each of our cells with billions of metal ions, including calcium, iron, copper and zinc. These ions facilitate critical biological functions.

However, too much of any metal can be toxic, while too little can cause disease. Our cells carefully monitor and control their metal content using a whole series of proteins that bind, sense and transport metal ions.

Keeping tabs on why and how metals flow into and out of our cells is a passion of Thomas O’Halloran Exit icon, professor of chemistry and molecular biosciences at Northwestern University in Illinois. For the past three decades, O’Halloran has investigated how fluctuations in the amount of metal ions inside cells influence gene expression, cell growth and other vital functions. Using a variety of approaches, he has uncovered new types of proteins that bind metal ions and investigated the role that imbalances in these ions play in a number of disease-related physiological processes.

One recent focus of his studies has been how zinc regulates oocyte (egg cell) maturation and fertilization. Ultimately, his work could help us better understand infertility, cancer and certain bacterial infections.

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Cool Image: Adding Color to the Gray World of Electron Microscopy

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Color electron micrograph of an endosome, a cell organelle. Credit: Ranjan Ramachandra, UCSD

As his Christmas gift to himself each year, the late biochemist Roger Tsien treated himself to two weeks of uninterrupted research in his lab. This image is a product of those annual sojourns. While it may look like a pine wreath dotted with crimson berries, it is in fact one of the world’s first color electron micrographs—and the method used to create it may dramatically advance cell imaging.

Electron microscopy (EM) is a time-honored technique for visualizing cell structures that uses beams of accelerated electrons to magnify objects up to 10 million times their actual size. Standard EM images are in grayscale and any color is added in with computer graphics programs after the image is made. With their new technique, Tsien, who received a Nobel Prize for his development of green fluorescent protein into a tool for visualizing details in living cells using light microscopes, and his colleagues have found a way to incorporate color labeling directly into EM. Continue reading “Cool Image: Adding Color to the Gray World of Electron Microscopy”

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There’s an “Ome” for That

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In the 13 years since the sequencing of the human genome, the list of “omes” has proliferated. Drop us a comment with your favorite ome—we may feature it in a follow-up post next month.

Have you ever collected coins, cards, toy trains, stuffed animals? Did you feel the need to complete the set? If so, then you may be a completist. A completist will go to great lengths to acquire a complete set of something.

Scientists can also be completists who are inspired to identify and catalog every object in a particular field to further our understanding of it. For example, a comprehensive parts list of the human body—and of other organisms that are important in biomedical research—could aid in the development of novel treatments for diseases in the same way that a parts list for a car enables auto mechanics to build or repair a vehicle.

More than 15 years ago, scientists figured out how to catalog every gene in the human body. In the years since, rapid advances in technology and computational tools have allowed researchers to begin to categorize numerous aspects of the biological world. There’s actually a special way to name these collections: Add “ome” to the end of the class of objects being compiled. So, the complete set of genes in the body is called the “genome,” and the complete set of proteins is called the “proteome.”

Below are three -omes that NIH-funded scientists work with to understand human health.

Genome

Illustration of the entire outer shell of the bacteriophage MS2. Credit: Wikimedia Commons, Naranson.

The genome is the original -ome. In 1976, Belgium scientists identified all 3,569 DNA bases—the As, Cs, Gs and Ts that make up DNA’s code—in the genes of bacteriophage MS2, immortalizing this bacteria-infecting virus as possessing the first fully sequenced genome.

Over the next two decades, a small handful of additional genomes from other microorganisms followed. The first animal genome was completed in 1998. Just 5 years later, scientists identified all 3.2 billion DNA bases in the human genome, representing the work of more than 1,000 researchers from six countries over a period of 13 years. Continue reading “There’s an “Ome” for That”

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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.

Continue reading “Metals in Medicine”
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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”

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Exploring the Evolution of Spider Venom to Improve Human Health

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Brown recluse

Female brown recluse spider. Credit Matt Bertone, North Carolina State University.

This Halloween, you’re not likely to see many trick-or-treaters dressed as spiders. Google Trends pegs “Spider” as the 87th most searched-for Halloween costume, right between “Hippie” and “The Renaissance.” But don’t let your guard down. Spiders are everywhere.

“I grew up on a farm in Indiana and had the luxury of exploring and turning over rocks and being curious. Any feelings of being grossed out by spiders were rapidly replaced by my feelings of awe for how amazing and diverse these creatures are.”– Greta Binford”

More than 46,000 species of spiders creepy crawl across the globe, on every continent except Antarctica. Each species produces a venom composed of an average of 500 distinct toxins, putting the conservative estimate of unique venom compounds at more than 22 million. This staggering diversity of venoms, collectively referred to as the venome, has only begun to be explored. Continue reading “Exploring the Evolution of Spider Venom to Improve Human Health”

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Interview With a Scientist: Laura Kiessling, Carbohydrate Scientist

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The outside of every cell on Earth—from the cells in your body to single-celled microorganisms—is blanketed with a coat of carbohydrates, or sugar molecules, that extend from the cell surface, branching off and bending as they interface with the extra-cellular space. The specific patterns in which these carbohydrates are arranged serve as an ID code that help cells recognize each other. For example, human liver cells have one pattern, while human red blood cells another. Certain diseases can even alter the pattern of surface carbohydrates, which is one way the body can recognize damaged cells. On foreign cells, including invading bacteria such as Streptococcus pneumoniae, the carbohydrate coat is even more distinct.

Laura Kiessling, a professor of chemistry at the University of Wisconsin, Madison, studies how carbohydrate coats are assembled and how cells use these coats to tell friend from foe. The implications of her research suggest strategies for targeting tumors, fighting diseases of inflammation and, as she discusses in this video, developing new classes of antibiotics.

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Newly Identified Cell Wall Construction Workers: A Novel Antibiotic Target?

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SEDS

A family of proteins abbreviated SEDS (bright, pink) help build bacterial cell walls, so they are a potential target for new antibiotic drugs. Credit: Rudner lab, Harvard Medical School.

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 Exit icon 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.