Viruses: Manufacturing Tycoons?

Pseudomonas chlororaphis

A computer image shows a bacterial cell invaded by a virus. The virus uses the cell to copy itself many times. It has built a protein compartment (red, rough circle surrounding the center) to house its DNA. Viral heads (blue, smaller pentagonal shapes spread through out) and tails (pink, rod shaped near the edges) are essential parts of a finished viral particle. The small, light blue particles are the bacterium’s own protein-making ribosomes. Credit: Vorrapon Chaikeeratisak, Kanika Khanna, Axel Brilot and Katrina Nguyen.

As inventors and factory owners learned during the Industrial Revolution, the best way to manufacture a lot of products is with an assembly line that follows a set of precisely organized steps employing many copies of identical and interchangeable parts. Some viruses are among life’s original mass producers: They use sophisticated organization principles to turn bacterial cells into virus particle factories.

Scientists at the University of California, San Diego, and the University of California, San Francisco, used cutting-edge techniques to watch a bacteria-infecting virus (bacteriophage) set up its particle-making factory inside a host cell.

The image above shows this happening inside a Pseudomonas chlororaphis, a soil-borne bacterium that protects plants against fungal pathogens. The virus builds a compartment (red, rough circle surrounding the center) that helps organize an assembly line for making copies of itself. The compartment looks like a cell nucleus, which bacteria do not have, and it functions like a nucleus by keeping activities that directly involve DNA separate from other cellular functions. Continue reading

Chasing Fireflies—and Better Cellular Imaging Techniques

firefly
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 terrestial examples, such as fireflies, glowworm insect larvae and foxfire fungi, and many more acquatic 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.

Bioluminescence is common across the tree of life (left to right): Panellus Stipticus (foxfire fungi); Lampryis noctiluca (glowworm insect); Aurelia Aurita (moon jellyfish). Credit: Wikimedia Commons, Ylem; Wikimedia Commons, Wofl; stock photo.

Every studied case of bioluminescence involves oxygen, a light-emitting pigment called luciferin and a protein called luciferase. Luciferase encourages the pigment’s reaction with oxygen, releasing energy in the form of light. Although many bioluminescent creatures have their own form of luciferase, they share just a handful of luciferins. For example, the luciferin called coelenterazine is found in many aquatic organisms. Continue reading

Interview With a Scientist: Namandjé Bumpus, Drug Metabolism Maven

Medications are designed to treat diseases and make us healthier. But our bodies don’t know that. To them, medications are merely foreign molecules that need to be removed.

Before our bodies can get rid of these drug molecules, enzymes in the liver do the chemical work of preparing the molecules for removal. There are hundreds of different versions of these drug-processing enzymes. Some versions work quickly, others work slowly. In some cases, the versions you have determine how well a medication works for you, and whether you experience side effects from it.

Namandjé Bumpus Exit icon, a researcher at Johns Hopkins University School of Medicine, is interested in how human bodies respond to HIV medications. She studies the enzymes that process these drugs. Her research team discovered that a genetic variant of a liver enzyme impacts the way some people handle a particular HIV drug. This variant is found in around 80 percent of people of European descent. She describes her work in this video.

Bumpus recently presented her research to a more scientifically advanced audience at an Early Career Investigator Lecture at the National Institutes of Health. Watch her talk titled Drug Metabolism, Pharmacogenetics and the Quest to Personalize HIV Treatment and Prevention.

Dr. Bumpus’ work is supported in part by NIGMS grant R01GM103853.

The Drama of Cell Death

spermatids

Spermatids—one stage in the formation of sperm—in the fruit fly (Drosophila). Credit: Sigi Benjamin-Hong, Rockefeller University (modified).

Although it looks like a bursting firework from a Fourth of July celebration, this image actually was created from pictures of spermatids—one stage in the formation of sperm—in the fruit fly (Drosophila). Drosophila is an organism that scientists often use as a model for studying how cells accomplish their amazing tasks. Drosophila studies can help reveal where an essential cellular process goes wrong in diseases such as autoimmune conditions or cancer. Cell death, or apoptosis, is one of these processes.

Almost every animal cell has the ability to destroy itself via apoptosis. Apoptosis is important because it allows the body both to develop normally and get rid of dangerous and unwanted cells when it needs to later in life, such as when cells become cancerous. Many different signals both within and outside the cell influence whether apoptosis happens when it should, and abnormal regulation of this process is associated with some diseases. Hermann Steller Exit icon and colleagues at Rockefeller University in New York City study Drosophila and mammalian cells to tease apart the steps of apoptosis and the many molecular signals that regulate it. Continue reading

Flipping the Switch on Controlling Disease-Carrying Insects

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

This image shows a mosquito egg. Wolbachia bacteria, which infect many species of insects including mosquitos, move from one generation to the next inside insect eggs. Credit: Wikimedia Commons, Mogana Das Murtey and Patchamuthu Ramasamy, Universiti Sains, Malaysia.

Suppressing insects that spread disease is an essential public health effort, and scientists are testing a possible new tool to use in this challenging arena. They’re harnessing a microbe capable of controlling insects’ reproductive processes.

The microbes, called Wolbachia, live inside the cells of about two-thirds of insect species worldwide, and they can manipulate the host’s reproductive cells in ways that boost their own survival. Scientists think they can use Wolbachia’s methods to reduce populations of insects that spread disease among humans.

A Switch to Control Fertility

Wolbachia have evolved complex ways to control insect reproduction so as to infect increasing numbers of an insect species—such as those prolific disease-spreaders, mosquitos. One method Wolbachia uses is called cytoplasmic incompatibility, or CI. The end result of CI, basically, is that the sperm of infected male insects cause sterility in uninfected females.

Wolbachia that have infected male insects can insert proteins that produce a kind of infertility switch into the host’s sperm. When the sperm later fuses with an egg from an uninfected female, the switch is triggered and renders the egg sterile. If the female is already infected, her eggs will contain Wolbachia, which can turn off the switch and allow the egg to develop. This trick ensures that more Wolbachia-infected insects will survive and continue to reproduce, while uninfected ones will be less successful.

Already, some states Exit icon and countries Exit icon are releasing Wolbachia-infected male mosquitoes into wild mosquito populations that carry disease-causing viruses to test this strategy for insect control. Males carrying a Wolbachia strain that strongly induces infertility in uninfected females should reduce the numbers of mosquito eggs that mature, leading to fewer mosquitos. Continue reading

Researchers Score Goal with New Atomic-Scale Model of Salmonella-Infecting Virus

An atomic-scale model of a virus that infects the Salmonella bacterium. Credit: C. Hryc and the Chiu Lab, Baylor College of Medicine.

This sphere could be a prototype design for the 2018 World Cup official match soccer ball, but you won’t see it dribbled around any soccer fields. The image is actually an atomic-scale model of a virus that infects the Salmonella bacterium. Like a soccer ball, both are approximately spherical shapes created by a combination of hexagonal (six-sided) and pentagonal (five-sided) units. Wah Chiu, a biochemist at Baylor College of Medicine, and his colleagues used new computational methods to construct the model from more than 20,000 cryo-electron microscopy (cryo-EM) images. Cryo-EM is a sophisticated technique that uses electron beams for visualizing frozen samples of proteins and other biological specimens.

The researchers’ model, published in a recent issue of PNAS, shows the virus’ protein shell, or capsid, that encloses the virus’ genetic material. Each color shows capsid proteins having the same interactions with their neighbors. The fine resolution allowed researchers to identify the protein interactions essential to building a stable shell. They developed a new approach to checking the accuracy and reliability of the virus model and reporting what parts are the most certain. The approach could be used to evaluate other complex biological structures, potentially leading to better quality models and new avenues for drug design and development.

This research is funded in part by NIH under grants R01GM079429, P01GM063210, P41GM103832, PN2EY016525, T15LM007093.

Sea Urchin Regeneration May Help Us Understand Aging

Sea urchin

The variegated sea urchin typically lives for about 4 years in the wild. The close-up view shows the sea urchin’s spines and tube feet that regrew after being removed 15 days earlier. Credit: Helena Reinardy (left) and Andrea Bodnar (right), Bermuda Institute of Ocean Sciences.

If you’ve ever been to the beach and walked around the rocks during low tide, you’ve probably seen a sea urchin. You may not have known that sea urchins found along the Pacific shore can live for more than 100 years. What’s even cooler is that, as they age, they don’t seem to lose their abilities to reproduce or regenerate damaged body parts. While different species of sea urchins have varying life expectancies, they all seem to share fountain-of-youth characteristics. For these and other reasons, scientists study sea urchins to investigate aging and other basic life processes. Continue reading

Beauty is in the Eye

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.

The Endoplasmic Reticulum: Networking Inside the Cell

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 imagining 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

New Technology May Help Reduce Serious and Costly Post-Surgical Infections—Using Nothing but Air

According to a recent estimate, implant infections following hip and knee replacement surgeries in the U.S. may number 65,000 by 2020, with the associated healthcare costs exceeding $1 billion. A new small, high-tech device could have a significant impact on improving health outcomes and reducing cost for these types of surgeries. The device, Air Barrier System (ABS), attaches on top of the surgical drape and gently emits HEPA-filtered air over the incision site. By creating a “cocoon” of clean air, the device prevents airborne particles—including the bacteria that can cause healthcare-associated infections—from entering the wound.

Air Barrier System
The Air Barrier System creates a “cocoon” of clean air (gray area with size indicated) over a surgical site to remove airborne contaminants and reduce the risk of infection in patients who are receiving an artificial hip, a blood vessel graft, a titanium plate in the spine or other implants.

Scientists recently analyzed the effectiveness of the ABS device in a clinical study Exit icon—funded by NIGMS—involving nearly 300 patients. Each patient needed an implant, such as an artificial hip, a blood vessel graft in the leg or a titanium plate in the spine. Because implant operations involve inserting foreign materials permanently into the body, they present an even higher risk of infection than many other surgeries, and implant infections can cause life-long problems.

The researchers focused on one of the most common causes of implant infections—the air in the operating room. Although operating rooms are much cleaner than almost any other non-hospital setting, it’s nearly impossible to sterilize the entire room. Instead, the scientists focused on reducing contaminants directly over the surgical site. They theorized that if the air around the wound was cleaner, the number of implant infections might go down. Continue reading