Tag: Cells

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Like a successful business networker, a cell’s endoplasmic reticulum (ER) is the structure that reaches out—quite literally—to form connections with many different parts of a cell. In several important ways, the ER enables those other parts, or organelles, to do their jobs. Exciting new images of this key member of the cellular workforce may clarify how it performs its roles. Such knowledge will also help studies of motor neuron and other disorders, such as amyotrophic lateral sclerosis (ALS), that are associated with abnormalities in ER functioning.

Structure Follows Function

Illustration of some of the jobs that the ER performs in the cell.

An illustration of some of the jobs that the endoplasmic reticulum (ER) performs in the cell. Some ER membranes (purple) host ribosomes on their surface. Other ER membranes (blue) extending into the cytoplasm are the site of lipid synthesis and protein folding. The ER passes on newly created lipids and proteins to the Golgi apparatus (green), which packages them into vesicles for distribution throughout the cell. Credit: Judith Stoffer.

Initiated in 1965, the Postdoctoral Research Associate Program (PRAT) is a competitive postdoctoral fellowship program to pursue research in one of the laboratories of the National Institutes of Health. PRAT is a 3-year program providing outstanding laboratory experiences, access to NIH’s extensive resources, mentorship, career development activities and networking. The program places special emphasis on training fellows in all areas supported by NIGMS, including cell biology, biophysics, genetics, developmental biology, pharmacology, physiology, biological chemistry, computational biology, immunology, neuroscience, technology development and bioinformatics

The ER is a continuous membrane that extends like a net from the envelope of the nucleus outward to the cell membrane. Tiny RNA- and protein-laden particles called ribosomes sit on its surface in some places, translating genetic code from the nucleus into amino acid chains. The chains then get folded inside the ER into their three-dimensional protein structures and delivered to the ER membrane or to other organelles to start their work. The ER is also the site where lipids—essential elements of the membranes within and surrounding a cell—are made. The ER interacts with the cytoskeleton—a network of protein fibers that gives the cell its shape—when a cell divides, moves or changes shape. Further, the ER stores calcium ions in cells, which are vital for signaling and other work.

To do so many jobs, the ER needs a flexible structure that can adapt quickly in response to changing situations. It also needs a lot of surface area where lipids and proteins can be made and stored. Scientists have thought that ER structure combined nets of tubules, or small tubes, with areas of membrane sheets. However, recent NIGMS PRAT (Postdoctoral Research Associate; see side bar) fellow Aubrey Weigel, working with her mentor and former PRAT fellow Jennifer Lippincott-Schwartz of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (currently at the Howard Hughes Medical Institute in Virginia) and colleagues, including Nobel laureate Eric Betzig, wondered whether limitations in existing imaging technologies were hiding a better answer to how the ER meets its surface-area structural needs in the periphery, the portion of the cell not immediately surrounding the nucleus. Continue reading “The Endoplasmic Reticulum: Networking Inside the Cell”

January 24, 2017March 5, 2021

Cool Tools: Pushing the Limits of High-Resolution Microscopy

by Alisa Zapp Machalek

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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”

December 19, 2016March 5, 2021

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

by Anne Oplinger

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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”

December 15, 2016March 5, 2021

There’s an “Ome” for That

by Chris Palmer

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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”

December 6, 2016March 5, 2021

The Irresistible Resistome: How Infant Diapers Might Help Combat Antibiotic Resistance (sort of)

by Alisa Zapp Machalek and Kathryn Calkins

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Credit: Pablo Tsukayama, Ph.D.,
Washington University School of Medicine

Gautam Dantas
Born: Mumbai, India
Most proud of: His family, which brings him joy and pride
Favorite lab tradition: OOFF! Official Optional Formal Fridays, when members of his lab can dress up, eat bread—made in the lab’s own bread machine—and drink beer and wine together at the end of the day
When not in the lab, he: Enjoys home brewing, pickling and canning, and spending time with his wife and children. He also attends musical performances, including those of his wife, who sings in the St. Louis Symphony Chorus
Advice to aspiring scientists: Pursue hobbies, take risks, explore beyond your comfort zone. “You can do a Ph.D., but also have other experiences.” He says his own outside activities refine his focus in the lab, keep him grounded and help him be an empathetic mentor to his students. Plus, he met his wife while singing in the chorus of Macalester College in St. Paul, Minnesota

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. Continue reading “The Irresistible Resistome: How Infant Diapers Might Help Combat Antibiotic Resistance (sort of)”

November 14, 2016March 5, 2021

Metals in Medicine

by Chris Palmer

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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. 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.

November 9, 2016March 5, 2021

NIGMS Is on Instagram!

by Alisa Zapp Machalek and Erin Ross

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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/ . 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.
#science

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#NCMIR

#UCSD

#smallbowel

#nutrients

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#anatomyphysiology

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

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#botany

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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
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#UCSD

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

#cell

#universityofwashington

November 2, 2016February 22, 2024

Lighting Up the Promise of Gene Therapy for Glaucoma

by Alisa Zapp Machalek

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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 (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”

October 12, 2016March 5, 2021

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

by Alisa Zapp Machalek

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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 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.

September 20, 2016March 5, 2021

The Extracellular Matrix, a Multitasking Marvel

by Ruchi Shah and Alisa Zapp Machalek

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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.

The extracellular matrix meets the needs of each body part. In teeth and bones, it’s rock-hard. In corneas, it’s a transparent gel that acts like a camera lens. In tendons, it forms strong fibers that bind muscle to bone. Credit: Stock image.

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. Continue reading “The Extracellular Matrix, a Multitasking Marvel”

Search this blog

Tag: Cells

The Endoplasmic Reticulum: Networking Inside the Cell

Cool Tools: Pushing the Limits of High-Resolution Microscopy

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

There’s an “Ome” for That

The Irresistible Resistome: How Infant Diapers Might Help Combat Antibiotic Resistance (sort of)

Metals in Medicine

NIGMS Is on Instagram!

Lighting Up the Promise of Gene Therapy for Glaucoma

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

The Extracellular Matrix, a Multitasking Marvel

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