Tag: Research Organisms

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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.

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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.
  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

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4 Timely Facts About Our Biological Clocks

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Illustration of circadian rhythm.
Genes and proteins run biological clocks that help keep daily rhythms in synch. Credit: Wikimedia Commons.

After you roll your clocks back by an hour this Sunday, you may feel tired. That’s because our bodies—more specifically, our circadian rhythms—need a little time to adjust. These daily cycles are run by a network of tiny, coordinated biological clocks.

NIGMS’ Mike Sesma tracks circadian rhythm research being conducted in labs across the country, and he shares a few timely details about our internal clocks:

1. They’re incredibly intricate.

Biological clocks are composed of genes and proteins that operate in a feedback loop. Clock genes contain instructions for making clock proteins, whose levels rise and fall in a regular cyclic pattern. This pattern in turn regulates the activity of the genes. Many of the results from circadian rhythm research this year have uncovered more parts of the molecular machinery that fine-tune the clock. Earlier in the month, we blogged about an RNA molecule that cues the internal clock.

2. Every organism has them—from algae to zebras.

Many of the clock genes and proteins are similar across species, allowing researchers to make important findings about human circadian processes by studying the clock components of organisms like fruit flies, bread mold and plants.

3. Whether we’re awake or asleep, our clocks keep ticking.

While they might get temporarily thrown off by changes in light or temperature, our clocks usually can reset themselves.

4. Nearly everything about how our body works is tied to biological clocks.

Our clocks influence alertness, hunger, metabolism, fertility, mood and other physiological conditions. For this reason, clock dysfunction is associated with various disorders, including insomnia, diabetes and depression. Even drug efficacy has been linked to our clocks: Studies have shown that some drugs might be more effective if given earlier in the day.

Learn more:
Circadian Rhythms Fact Sheet

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Meet Scott Poethig

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Scott Poethig
Fields: Plant biology, cell and developmental biology, genetics
Works at: University of Pennsylvania
Studied at: College of Wooster, Yale University
Favorite musicians: Nick Drake and Bruce Springsteen
High school job: Radio D.J.
Favorite book: “The Little Prince,” by Antoine de Saint-Exupéry

When Scott Poethig signed up for a developmental biology course in his senior year of college, he expected to learn how organisms transition from single cells to juveniles to adults. He did not expect to learn just how much scientists still didn’t know about this process.

“It was the first course I had taken as an undergraduate where I felt that I could ask a question that there wasn’t an answer to already,” he recalls. “I thought, ‘Wow! This is amazing.’”

Poethig already had an interest in plant biology and an independent research project studying corn viruses. He immediately saw the potential in combining his knowledge of plants with his questions about how organisms grow. “There seemed to be a lot of low hanging fruit in plant development,” he says.

Today, Poethig is the head of a plant development lab at the University of Pennsylvania. His work probes the complex molecular mechanisms that drive the transition from a young seedling to an adult plant that hasn’t yet produced seeds.

“The analogous period in human development is the interval between birth and puberty,” he explains. “People think of puberty as the major developmental transition in postnatal human development, but a lot of change happens before that point.”

His Findings

Poethig discovered that for the mustard plant Arabidopsis, a model organism frequently studied by geneticists, change begins early. Before these plants begin to flower—a sign of reproductive maturity—they undergo a process of vegetative maturation. In Arabidopsis, Poethig found that juvenile plants can be distinguished from adult plants by where hairs are produced on a leaf. Juvenile plants only produce hairs on the upper surface of the leaf, whereas adult plants produce leaves with hairs on both the upper and lower surfaces.

By studying mutant Arabidopsis plants where the adult pattern of hair development is either delayed or advanced, Poethig identified microRNAs as key players in this developmental transition.

MicroRNA molecules commonly block the expression of specific genes. Poethig found that in Arabidopsis, a type of microRNA prevents development. Young plants have high levels of this microRNA and cannot fully mature. When those levels drop, plants progress to adulthood.

MicroRNAs similarly control development in the nematode C. elegans. Scientists study the genetics of this tiny worm to better understand related developmental processes in more complex organisms. Because plants also use microRNAs to regulate development, Poethig’s discoveries may contribute to our understanding of how these molecules govern development in animals, including humans.

Poethig now wants to learn what determines the timing of developmental changes. He asks: “Why do microRNA levels drop? What’s the signal that causes that? What is the plant measuring?” His current hypothesis: sugar.

In a recent study, he found that giving plants additional sugar reduced microRNA levels and sped up development. Meanwhile, mutant plants that couldn’t produce enough sugar on their own through photosynthesis had increased microRNA levels and delayed development compared to normal plants.

This research may one day advance our understanding of how nutrition and genetics interact to affect human development. “In essentially all organisms, aging and the timing of developmental processes are strongly affected by nutrition,” Poethig explains. “In humans, childhood obesity is sometimes associated with early puberty, and it is important to understand the molecular basis for this effect.”

Poethig believes that studying microRNAs in plants may also lead to discoveries in human genetics outside of developmental biology. “MicroRNAs control a wide range of gene activity in plants and animals,” Poethig explains. “In humans, these molecules control the activity of as many as 30 percent of our genes. So understanding how microRNAs work in plants could help us understand their function in humans.”

Besides studying the Arabidopsis plants in his lab, Poethig also studies the plants in his kitchen, and uses his fascination with the history, culture and politics of food to excite others about science. Watch video.

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Cool Image: Researching Regeneration in a Model Organism

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The isolated feeding tube of a flatworm.

The feeding tube, or pharynx, of a planarian worm with cilia shown in red and muscle fibers shown in green. Credit: Carrie Adler/Stowers Institute for Medical Research.

This rainbow-hued image shows the isolated feeding tube, or pharynx, of a tiny freshwater flatworm called a planarian, with the hairlike cilia in red and muscle fibers in green. Scientists use these wondrous worms, which have an almost infinite capacity to regrow all organs, as a simple model system for studying regeneration. A research team led by Alejandro Sánchez Alvarado of the Stowers Institute for Medical Research exploited a method known as selective chemical amputation to remove the pharynx easily and reliably. This allowed the team to conduct a large-scale genetic analysis of how stem cells in a planaria fragment realize what’s missing and then restore it. The researchers initially identified about 350 genes that were activated as a result of amputation. They then suppressed those genes one by one and observed the worms until they pinpointed one gene in particular—a master regulator called FoxA—whose absence completely blocked pharynx regeneration. Scientists believe that researching regeneration in flatworms first is a good way to gain knowledge that could one day be applied to promoting regeneration in mammals.

Learn more:
Stowers Institute News Release
Sánchez Lab

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NIH Director Blogs About Value of Model Organisms in Drug Discovery Research

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(Left) Untreated yeast cells, (Right) Treated yeast cells. Credit: Daniel Tardiff, Whitehead Institute.
Treating yeast cells with the NAB compound reverses the toxic effects of elevated levels of alpha synuclein protein. Credit: Daniel Tardiff, Whitehead Institute. View larger image

These eye-catching images and the NIGMS-funded research that yielded them were recently featured by NIH Director Francis Collins on his blog. Scientists led by a team at the Whitehead Institute for Biomedical Research engineered yeast to produce too much of a protein, alpha synuclein. In Parkinson’s disease, elevated levels or mutated forms of this protein wreak havoc on the cell. Using the model system, the researchers tested tens of thousands of compounds to identify any that reversed the toxic effects. One did. The compound, abbreviated NAB, worked similarly in an animal model and in rat neurons grown in a lab dish. Collins described the approach as “an innovative strategy for drug hunting that will likely be extended to other conditions.”