Feeling Out Bacteria’s Sense of Touch

Our sense of touch provides us with bits of information about our surroundings that inform the decisions we make. When we touch something, our nervous system transmits signals through nerve endings that feed information to our brain. This enables us to sense the stimulus and take the appropriate action, like drawing back quickly when we touch a hot stovetop.

Bacteria are single cells and lack a nervous system. But like us, they rely on their “sense” of touch to make decisions—or at least change their behavior. For example, bacteria’s sense of touch is believed to trigger the cells to form colonies, called biofilms, on surfaces they make contact with. Bacteria may form biofilms as a way to defend themselves, share limited nutrients, or simply to prevent being washed away in a flowing liquid.

Humans can be harmed by biofilms because these colonies serve as a reservoir of disease-causing cells that are responsible for high rates of human infection. Biofilms can protect at least some cells from being affected by antibiotics. The surviving reservoir of bacteria then have more time to evolve resistance to antibiotics.

At the same time, some biofilms can be valuable; for example, they help to break down waste in water treatment plants and to drive electrical current as part of microbial fuel cells.

Until recently, scientists thought that bacteria formed biofilms and caused infections in response to chemical signals they received from their environments. But research in 2014 showed that the bacterium Pseudomonas aeruginosa could infect a variety of living tissues—from plants to many kinds of animals—simply by making contact with them. In the past year, multiple groups of investigators have learned more about how bacteria sense that they have touched a surface and how that sense translates to changes in their behavior. This understanding could lead to new ways of preventing infections or harmful biofilm formation.

Making Contact

Pili (green) on cells from the bacterium Caulobacter crescentus (orange). Scientists used a fluorescent dye to stain pili so they could watch the structures extend and retract. Credit: Courtney Ellison, Indiana University.

When they first make contact with a surface, bacteria change from free-ranging, swimming cells to stationary ones that secrete a sticky substance, tethering them in one place. To form a biofilm, they begin replicating, creating an organized mass stable enough to resist shaking and to repel potential invaders (see https://biobeat.nigms.nih.gov/2017/01/cool-image-inside-a-biofilm-build-up/).

How do swimming bacteria sense that they have found a potential surface to colonize? Working with the bacterium Caulobacter crescentus, Indiana University Ph.D. student Courtney Ellison and her colleagues, under the direction of professor of biology and NIGMS grantee Yves Brun Exit icon, recently showed that hair-like structures on the cell’s surface, called pili, play a role here. The researchers found that as a bacterial cell swims in a fluid, its pili are constantly stretching out and retracting. When the cell makes contact with a surface, the pili stop moving, start producing a sticky substance and use it to hold onto the surface. Continue reading “Feeling Out Bacteria’s Sense of Touch”

The Changing Needs of a Cell: No Membrane? No Problem!

Russian nesting dolls. Credit: iStock.

How “membrane-less” organelles help with key cellular functions

Scientists have long known that animal and plant cells have specialized subdivisions called organelles. These organelles are surrounded by a semi-permeable barrier, called a membrane, that both organizes the organelles and insulates them from the rest of the cell’s mix of proteins, salt, and water. This set-up helps to make cells efficient and productive, aiding in energy production and other specialized functions. But, because of their semi-permeable membranes, organelles can’t regroup and reform in response to stress or other outside changes. Cells need a rapid response team working alongside the membrane-bound organelles to meet these fluctuating needs. Until recently, who those rapid responders were and how they worked has been a mystery.

Recent research has led biologists to learn that the inside of a cell or an organelle is not just a lot of different molecules dissolved in water. Instead, we now know that cells contain many pockets of liquid droplets (one type of liquid surrounded by a liquid of different density) with specialized composition and function that are not surrounded by membranes. Because these “membrane-less organelles” are not confined, they can rapidly come together in response to chemical signals, such as those that indicate stress, and equally rapidly fall apart when they are no longer needed, or when the cell is about to divide. This enables membrane-less organelles to be “rapid responders.” They can have complex, multilayered structures that help them to perform many critical cell functions with multiple steps, just like membrane-bound organelles. Scientists even suspect that the way these organelles form as droplets may shed light on how life on Earth first took shape (see sidebar “Could This Be How Life First Took Shape?” at bottom of page).

The Many Membrane-less Organelles

Scientists have identified more than a dozen membrane-less organelles at work in mammalian cells. Several kinds found inside the nucleus—including nuclear speckles, paraspeckles, and Cajal bodies—help with cell growth, stress response, the metabolizing (breaking down) of RNA, and the control of gene expression—the process by which information in a gene is used in the synthesis of a protein. Out in the cytoplasm, P-bodies, germ granules, and stress granules are membrane-less organelles that are involved in metabolizing or protecting messenger RNA (mRNA), controlling which mRNAs are made into proteins, and in maintaining balance, or homeostasis, of the cell’s overall health.

The nucleolus, located inside the nucleus, is probably the largest of the membrane-less organelles. It acts as a factory to assemble ribosomes, the giant molecular machines that “translate” messenger RNAs to make all cellular proteins. Continue reading “The Changing Needs of a Cell: No Membrane? No Problem!”

Zebrafish Scrapbook

Name: Danio rerio Hometown: Freshwater ponds and rivers of India, Nepal, and neighboring countries Occupation: Research Long-term goal: Solving the basic mysteries of life Work site: More than 600 science labs worldwide
Danio rerio That’s me and some other zebrafish, swimming in a tank in one of the more than 600 labs around the world that use us to study embryo development, genetics, and all kinds of human diseases. Credit: Wikimedia Commons, Azul.

Apart from the tell-tale stripes that give me my nickname, zebrafish, I look a lot like your standard minnow swimming in the shallows of any pond, lake, or river. But I like to think I’m more important than that. In fact, researchers around the world have turned to me and my extended family to understand some of the most basic mysteries of life. From studying us, they’re learning about how embryos develop, how cancer works, and whether someday humans might be able to rebuild a heart, repair a spinal cord injury, or regrow a severed limb.

Why us? Because zebrafish are pretty special and researchers think we’re easy to work with. First, unlike your standard lab mouse or rat, we lay lots of eggs, producing baby fish that grow up fast. We develop outside our mothers and go from egg to embryo to free-swimming larva in just 3 days (check out this video Exit icon of how we grow, cell by cell, during the first 24 hours). Within 3 months, we’re fully mature.

Not only do zebrafish moms have many babies at the same time, and not only do these babies grow up quickly, but our eggs and embryos are see-through, so scientists can literally watch us grow one cell at a time. We stay mostly transparent for a few weeks after hatching. That makes it super easy for scientists to monitor us for both normal and abnormal development. In fact, scientists have learned how to turn off the genes that give our skin its color. These zebrafish, named casper, after the “friendly ghost” of cartoon fame, stay semi-transparent, or translucent, through adulthood.

And last, but certainly not least, did I mention that we can regenerate? If parts of my body are damaged, even to a significant degree, they can regrow. This holds true for my heart, fins, spinal cord, and even brain tissue. Our regenerative capacity is seemingly unlimited; my caudal fin, for example, can grow back dozens of times. Continue reading “Zebrafish Scrapbook”

“Selfish” Gene Enhances Own Transmission at Expense of Organism’s Fertility

These glowing images of yeast (Schizosaccharomyces kambucha) reproductive cells show an example of a selfish gene at work.
These glowing images of yeast (Schizosaccharomyces kambucha) reproductive cells show an example of a selfish gene at work. Here, the selfish gene boosts its chances of being passed to the next generation by producing both a toxin (stained cyan) and an antitoxin (stained magenta). Cells with a copy of the selfish gene are protected by the antitoxin, left and bottom ovals. Those without the selfish gene are destroyed by the toxin. Scientists suspect that selfish genes could be operating throughout many organisms’ genomes, possibly having a major impact on how genetic material is inherited over generations. Credit: Image courtesy of María Angélica Bravo Núñez and Nicole Nuckolls.

There’s an old saying that rules are meant to be broken. In the 1860s, Gregor Mendel found that each copy of a gene in an organism has an equal chance of being passed to the next generation. According to this simple rule, each version of a gene gets passed to offspring with the same frequency. The natural selection process can then operate efficiently, favoring the genes that produce an advantage for an organism’s survival or reproductive success and, over successive generations, eliminating genes from the gene pool that bring a disadvantage.

Of course, the way organisms inherit genes is not as straightforward as Mendel’s work predicted. In natural systems, inheritance often fails to follow the rules. One culprit scientists are identifying again and again are what are called “selfish genes”: one or more genes that have evolved a method of skewing inheritance in their favor.

Scientists refer to these selfish genes—which are often complexes of multiple genes working together—as “selfish” because they enhance their own transmission to the next generation, sometimes by killing off any of the organism’s reproductive cells that lack copies of those genes. Using a variety of techniques, the genes are effective at passing themselves on to future generations. However, their methods set up a conflict within the organism by damaging its fertility; overall, fewer reproductive cells or offspring survive to produce a new generation.

Selfish genes are a challenge for scientists to identify, but researchers say that knowing more about these genes could help explain a range of genetic mysteries, from causes of infertility to details on how species evolve. The methods these genes use could also be harnessed to help control the reproduction of certain populations such as mosquitos that spread disease.

One recently described selfish gene system is found in the yeast cells pictured above. Sarah Zanders Exit icon and her colleagues at the Stowers Institute for Medical Research in Kansas City, Missouri, and the Fred Hutchinson Cancer Research Center in Seattle, Washington, study selfish gene systems in yeast to understand how common they are and how they affect a species’ fertility and evolution. “Usually we think about infertility stemming from the good guys failing. For example, a gene that normally promotes fertility could be mutated so that it can no longer do its job,” says Zanders. “But selfish genes are another potential source of infertility. Learning general principles about selfish genes in simple models will guide future searches for selfish genes that could be contributing to human infertility.”

Recently, the scientists discovered a single selfish gene, wtf4, that encodes both a toxin and an antitoxin protein. When yeast produce their reproductive cells, called spores, the wtf4 toxin protein is released into the immediate vicinity, but the antitoxin remains inside spores that contain a copy of wtf4. The toxin destroys all the spores that don’t have the antitoxin protein. Although the yeast has fewer spores—and therefore reduced fertility—each spore carries wtf4, ensuring that the gene will be passed to the next generation of yeast. Continue reading ““Selfish” Gene Enhances Own Transmission at Expense of Organism’s Fertility”

RISE-ing Above: Embracing Physical Disability in the Lab

This is the fourth post in a new series highlighting NIGMS’ efforts toward developing a robust, diverse and well-trained scientific workforce.

Marina Nakhla

Marina Z. Nakhla
Hometown: West Los Angeles, California
Blogs For: Ottobock “Life in Motion,” Exit icon a forum for the amputee community, where she’s covered topics ranging from medical insurance to dating.
Influential Book: The Catcher in the Rye by J.D. Salinger
Favorite TV Show: Grey’s Anatomy
Languages: English and Arabic
Unusual Fact: Gets a new pair of legs every year or two

Nakhla at her graduation from California State University, Northridge, where she graduated with a B.A. in psychology with honors. She is currently a second-year master’s student there studying clinical psychology. Credit: Christina Nakhla.

When Marina Z. Nakhla was just a toddler, she lost both of her legs. Now 22 and a graduate student at California State University, Northridge (CSUN), she has hurdled obstacles most of us never face.

Nakhla conducts research to better understand the decrease in mental abilities experienced by people with brain diseases. She is a scholar in CSUN’s Research Initiative for Scientific Enhancement (RISE) Program. This training program aims to enrich and diversify the pool of future biomedical researchers. Her long-term goal is to earn a Ph.D., to work as a clinical psychologist and to continue conducting research in neuropsychology. Along the way, she aspires to be a leader to her peers and an advocate for underrepresented people, particularly those with disabilities.

I first learned about Nakhla from an email message titled “CSUN RISE Student.” The acronym, pronounced “see [the] sun rise,” is an apt motto for a program that prepares students for a bright future in science. I believe it also encapsulates Nakhla’s positive, forward-looking mindset, despite the obstacles she has faced. Here’s her story:

Q: What got you interested in science?

A: Growing up, I was always drawn to science. I enjoyed learning how things work. I first became interested in psychology after reading The Catcher in the Rye in high school. I was so intrigued by Holden Caulfield’s thought processes and experiences of alienation and depression, despite the fact that he came from a wealthy family and went to a good school.

Why are some people more prone to experiencing depression? Why are some peoples’ thought processes so different than others? What factors contribute to resiliency? How can we help these people? These questions also made me think about the significant adversities that I had personally experienced. My desire to know more about the brain, as well as my personal experiences, instilled my passion to make a difference in others’ lives through science. Continue reading “RISE-ing Above: Embracing Physical Disability in the Lab”

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.

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

Cool Tools: Pushing the Limits of High-Resolution Microscopy

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”

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

Gautam Dantas
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 10th 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 Exit icon, 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)”

NIGMS Is on Instagram!

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.
#science Exit icon #biology Exit icon #research Exit icon #cells Exit icon #cellbiology Exit icon #microscopy Exit icon #nigms Exit icon #scienceisbeautiful Exit icon #sciart Exit icon #nigms Exit icon #nih Exit icon #NCMIR Exit icon #UCSD Exit icon #smallbowel Exit icon  #nutrients Exit icon #nutrient Exit icon #anatomyphysiology Exit icon

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