Tag: Research Organisms

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Interview With a Scientist: Janet Iwasa, Molecular Animator

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The world beneath our skin is full of movement. Hemoglobin in our blood grabs oxygen and delivers it throughout the body. Molecular motors in cells chug along tiny tubes, hauling cargo with them. Biological invaders like viruses enter our bodies, hijack our cells and reproduce wildly before bursting out to infect other cells.

To make sense of the subcutaneous world, Janet Iwasa, a molecular animator at the University of Utah, creates “visual hypotheses”—detailed animations that convey the latest thinking of how biological molecules interact.

“It’s really building the animated model that brings insights,” Iwasa told Biomedical Beat in 2014. “When you’re creating an animation, you’re really grappling with a lot of issues that don’t necessarily come up by any other means. In some cases, it might raise more questions, and make people go back and do some more experiments when they realize there might be something missing.”

Iwasa has collaborated with numerous scientists to develop animations of a range of biological processes and structures Exit icon. Recently, she’s undertaken an ambitious, multi-year project to animate HIV reproduction Exit icon.

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Interview With a Slime Mold: Racing for New Knowledge

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Dictyostelium discoideum
Credit: Wikimedia Commons, Usman Bashir.
Dictyostelium discoideum
Natural habitat: Deciduous forest soil and moist leaf litter
Favorite food: Bacteria
Top speed: 8 micrometers per minute

Like the athletes in Rio, the world’s most highly advanced microbial runners recently gathered in Charlestown, Massachusetts, to find out which ones could use chemical cues to most quickly navigate a maze-like microfluidic racecourse. The winners’ prize: credit for helping scientists learn more about how immune system cells navigate through the human body on their way to fight disease.

The finalists were a group of soil-dwelling slime molds called Dictyostelium that were genetically engineered by a pair of Dutch biochemists to detect minuscule chemical changes in the environment. The racers used their enhanced sense of “smell” to avoid getting lost on their way to the finish line.

While researchers have been racing the genetically souped-up microbes at annual events for a few years—another competition is scheduled for October 26—scientists have been studying conventional Dictyostelium for decades to investigate other important basic life processes including early development, gene function, self/non-self recognition, cell-type regulation, chemical signaling and programmed cell death. Continue reading “Interview With a Slime Mold: Racing for New Knowledge”

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Visualizing Skin Regeneration in Real Time

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Top: Colorful skin cells on a zebrafish . Bottom: Cells from the outer surface of the scale.
More than 70 Skinbow colors distinguish hundreds of live cells from a tiny bit (0.0003348 square inches) of skin on the tail fin of an adult zebrafish. The bottom image shows the cells on the outer surface of a scale. Credit: Chen-Hui Chen, Duke University.

Zebrafish, blue-and-white-striped fish that are about 1.5 inches long, can regrow injured or lost fins. This feature makes the small fish a useful model organism for scientists who study tissue regeneration.

To better understand how zebrafish skin recovers after a scrape or amputation, researchers led by Kenneth Poss of Duke University tracked thousands of skin cells in real time. They found that lifespans of individual skin cells on the surface were 8 to 9 days on average and that the entire skin surface turned over in 20 days.

The scientists used an imaging technique they developed called “Skinbow,” which essentially shows the fish’s outer layer of skin cells in a spectrum of colors when viewed under a microscope. Skinbow is based on a technique created to study nerve cells in mice, another model organism.

The research team’s color-coded experiments revealed several unexpected cellular responses during tissue repair and replacement. The scientists plan to incorporate additional imaging techniques to generate an even more detailed picture of the tissue regeneration process.

The NIH director showcased the Skinbow technique and these images on his blog, writing: “You can see more than 70 detectable Skinbow colors that make individual cells as visually distinct from one another as jellybeans in a jar.”

This work was funded in part by NIH under grant R01GM074057.

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Another Piece to a Century-Old Evolutionary Puzzle

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After mating about 55,000 pairs of fruit flies and sifting through 333,000 daughter flies, a research team found six sons that each had mutations in the same gene that helped make two fruit fly species unique from each other. Credit: Jim Woolace, Fred Hutch News Service.

Nitin Phadnis and Harmit Malik set out to conduct an experiment that could solve a century-old evolutionary puzzle: How did two related fruit fly species arise from one? Years after they began their quest, they finally have an answer.

The existence of a gene that helps make each of these fruit fly species unique and separate from each other had been guessed at since 1940, following experiments decades earlier in which geneticists first noticed that the two types of flies, when mated, had only daughters—no sons.

Scientists had previously discovered two other genes involved in driving the fruit fly species apart, but they knew those two genes weren’t the full story.

Continue reading “Another Piece to a Century-Old Evolutionary Puzzle”
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Cool Image: A Circadian Circuit

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Clock neurons (middle right, right corner and edge), leucokinin (LK) neurons (top left, top right and bottom middle), leucokinin receptor (LK-R) neurons (top left, top right and bottom middle)

This image, taken with a confocal microscope, shows how time-of-day information flows through the fruit fly brain. Clock neurons (stained in blue) communicate with leucokinin (LK) neurons (stained in red at the top left, top right and bottom middle), which, in turn, signal to leucokinin receptor (LK-R) neurons (stained in green). This circuit helps regulate daily activity in the fly. Credit: Matthieu Cavey and Justin Blau, New York University.

Feeling sleepy and dazed after the switch to daylight savings time this weekend? Your internal clocks are probably a little off and need some time to adjust.

Researchers have been studying biological clocks for decades to figure out how they control circadian rhythms, the natural 24-hour pattern of physical, mental and behavioral changes that affect sleep, appetite and metabolism. Knowing more about what makes our clocks tick could help researchers develop better therapies for sleep problems, metabolic conditions and other disorders associated with mistimed internal clocks. Continue reading “Cool Image: A Circadian Circuit”

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Seeing Telomerase’s ‘Whiskers’ and ‘Toes’

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Telomerase and its components.

The image here is the “front view” of telomerase, with the enzyme’s components shown in greater detail than ever before. Credit: UCLA Department of Chemistry and Biochemistry.

Like the features of a cat in a dark alley, those of an important enzyme called telomerase have been elusive. Using a combination of imaging techniques, a research team led by Juli Feigon Exit icon of the University of California, Los Angeles, has now captured the clearest view ever of the enzyme.

Telomerase maintains the DNA at the ends of our chromosomes, known as telomeres, which act like the plastic tips on the ends of shoelaces. In the absence of telomerase activity, telomeres get shorter each time our cells divide. Eventually, the telomeres become so short that the cells stop dividing or die. On the other hand, cells with abnormally high levels of telomerase activity can constantly rebuild their protective chromosomal caps. Telomerase is particularly active within cancer cells. Continue reading “Seeing Telomerase’s ‘Whiskers’ and ‘Toes’”

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Interview With a Worm: We’re Not So Different

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Planarian
Credit: Alejandro Sánchez Alvarado, Stowers Institute for Medical Research.
Schmidtea mediterranea
Home: Freshwater habitats along the Mediterranean
Party trick: Regenerating its head
Most charismatic feature: Eyespots
Work site: Science labs worldwide

The planarian has a power few creatures can match. Remove its head, its tail or nearly any of its body parts, and this aquatic flatworm will simply grow it back. Humans can’t do that, of course. And yet many of the genes that help the planarian regenerate are also found in us. To learn more about this tiny marvel, we “interviewed” a representative. Continue reading “Interview With a Worm: We’re Not So Different”

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Food for Thought: Nutrient-Detecting Brain Sensor in Flies

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If you participated in a cupcake taste test, do you think you’d be able to distinguish a treat made with natural sugar from one made with artificial sweetener? Scientists have known for decades that animals can tell the difference, but what’s been less clear is how.

Fruit fly neurons in the brain (red) with nerve fibers (white) that extend to the gut.
For fruit flies, nutritive sugars activate a set of neurons in the brain (red) with nerve fibers (white) that extend to the gut. Credit: Jason Lai and Greg Suh, New York University School of Medicine.

Now, researchers at the New York University School of Medicine have identified a collection of specialized nerve cells in fruit flies that acts as a nutrient-detecting sensor, helping them select natural sugar over artificial sweetener to get the energy they need to survive.

“How specific sensory stimuli trigger specific behaviors is a big research question,” says NIGMS’ Mike Sesma. “Food preferences involve more than taste and hunger, and this study, which was done in an organism with many of the same cellular components as humans, gives us a glimpse of the complex interplay among the many factors.”

The study, described in the July 15 issue of Neuron, builds on the researchers’ earlier studies of feeding behavior that showed hungry fruit flies, even ones lacking the ability to taste, selected calorie-packed sugars over zero-calorie alternatives. The scientists, led by Greg Suh and Monica Dus Exit icon, suspected that the flies had a molecular system for choosing energy-replenishing foods, especially during periods of starvation. Continue reading “Food for Thought: Nutrient-Detecting Brain Sensor in Flies”

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Field Focus: Our Microbial Menagerie

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Trillions of microorganisms inhabit us—inside and out. Scientists are surveying these microbial metropolises to learn more about their role in health. Microbiologists Darren Sledjeski of NIGMS and Andrew Goodman Exit icon of Yale University share a few details of what researchers have learned so far.

Vitruvian man filled with bacteria.
Researchers are surveying the microbes that inhabit us to learn more about their role in health. Credit: Andrew Goodman, Yale University.
  1. The majority of the microbes that inhabit us are bacteria. The rest of the microbial menagerie is fungi and viruses, including ones that infect the bacteria! Collectively, our resident microorganisms are referred to as the human microbiota, and their genomes are called the human microbiome.
  2. Our bodies harbor more bacterial cells than human ones. Even so, the microbiota accounts for less than 3 percent of a person’s body mass. That’s because our cells are up to 10,000 times bigger in volume than bacterial cells.
  3. Your collection of bacteria has more genes than you do. Scientists estimate that the genomes of gut bacteria contain 100-fold or more genes than our own genomes. For this reason, the human microbiome is sometimes called our second genome.
  4. Most of our microbes are harmless, and some are helpful. For example, harmless microbes on the skin keep infectious microbes from occupying that space. Microbes in the colon break down lactose and other complex carbohydrates that our bodies can’t naturally digest.
  5. Different microbes occupy different parts of the body. Some skin bacteria prefer the oily nooks near the nose, while others like the dry terrain of the forearm. Bacteria don’t all fare well in the same environment and have adapted to live in certain niches. The NIGMS Findings Magazine article Body Bacteria: Exploring the Skin’s Microbial Metropolis shows what types of bacteria colonize where.
Screenshot from the iBiology video.
Are we more microbial than human? Richard Losick, a microbiologist at Harvard University, explores that question in this video lecture produced by iBiology Exit icon.
  1. Each person’s microbiota is unique. The demographics of microbiota differ among individuals. Diet is one reason. Also, while a type of microbe might be part of one person’s normal microbial flora, it might not be part of another’s, and could potentially make that person sick.
  2. Host-microbial interactions are universal. Microbial communities may vary from person to person, but everyone’s got them, including other creatures. For this reason, researchers can use model organisms to tease apart the complexities of host-microbial interactions and develop broad principles for understanding them. The mouse is the most widely used animal model for microbiome studies.
  3. The role of microbiota in our health isn’t entirely clear. While it’s now well accepted that the microbial communities that inhabit us are actively involved in a range of conditions—from asthma to obesity—research studies have not yet pinpointed why or how. In other words, the results may suggest that the presence of a bacterial community is associated with a disease, but they don’t show cause and effect.
  4. Most of our microbes have not been grown in the lab. Microbes require a certain mix of nutrients and other microbes to survive, making it challenging to replicate their natural environments in a petri dish. New culturing techniques are enabling scientists to study previously uncultivated microbes.
  5. The impact of probiotic and prebiotic products isn’t clear. Fundamental knowledge gaps remain regarding how these products may work and what effects they might have on host-microbial interactions. A new NIH effort to stimulate research in this area is under way.
  6. There’s even more we don’t know! Additional areas of research include studying the functions of microbial genes and the effects of gut microbes on medicines. The more we learn from these and other studies, the more we’ll understand how our normal microbiota interacts with us and how to apply that knowledge to promote our health.
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How Instructions for Gene Activity Are Passed Across Generations

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C. elegans embryos
Images of C. elegans embryos show transmission of an epigenetic mark (green) during cell division from a one-cell embryo (left) to a two-cell embryo (right). Credit: Laura J. Gaydos.

Chemical tags that cells attach to DNA or to DNA-packaging proteins across the genome—called epigenetic marks—can alter gene activity, or expression, without changing the underlying DNA code. As a result, these epigenetic changes can influence health and disease. But it’s a matter of debate as to whether and how certain epigenetic changes on DNA-packaging proteins can be passed from parents to their offspring.

In studies with a model organism, the worm C. elegans, researchers led by Susan Strome of the University of California, Santa Cruz, have offered new details that help resolve the debate.

Strome’s team created worms with a genetic change that knocks out the enzyme responsible for making a particular methylation mark, a type of epigenetic mark that can turn off gene expression at certain points of an embryo’s development. Then the scientists bred the knockout worms with normal ones. Looking at the chromosomes from the resulting eggs, sperm and dividing cells of embryos after fertilization, the researchers found that the methylation marks are passed from both parents to offspring. The enzyme, however, is passed to the offspring just by the egg cell. For embryos with the enzyme, the epigenetic marks are passed faithfully through many cell divisions. For those without it, the epigenetic mark can be passed through a few cell divisions.

Because all animals use the same enzyme to create this particular methylation mark, the results have implications for parent-to-child epigenetic inheritance as well as cell-to-cell inheritance in other organisms.

This work was funded in part by NIH under grants R01GM034059, T32GM008646 and P40OD010440.

Learn more:

University of California, Santa Cruz News Release
Dynamic DNA Section from The New Genetics Booklet