Interview with a Scientist: Jeramiah Smith on the Genomic Antics of an Ancient Vertebrate

The first known descriptions of cancer come from ancient Egypt more than 3,500 years ago. Early physicians attributed the disease to several factors, including an imbalance in the body’s humoral fluids, trauma, and parasites. Only in the past 50 years or so have we figured out that mutations in critical genes are often the trigger. The sea lamprey, a slimy, snake-like blood sucker, is proving to be an ideal tool for understanding these mutations.

The sea lamprey, often called the jawless fish, is an ancient vertebrate whose ancestor diverged from the other vertebrate lineages (fish, reptiles, birds and mammals) more than 500 million years ago. Jeramiah Smith,Link to external web site associate professor of biology at the University of Kentucky, has discovered that lamprey have two separate genomes: a complete genome specific to their reproductive cells, consisting of 99 chromosomes (humans have 23 pairs) and another genome in which about 20 percent of genes have been deleted after development. Using the lamprey model, Smith and his colleagues have learned that many of these deleted genes—such as those that initiate growth pathways—are similar to human oncogenes (i.e., cancer-causing genes).

Continue reading

Genomic Gymnastics of a Single-Celled Ciliate and How It Relates to Humans

Laura Landweber
Credit: Denise Applewhite.
Laura Landweber
Grew up in: Princeton, New Jersey
Job site: Columbia University, New York City
Favorite food: Dark chocolate and dark leafy greens
Favorite music: 1940’s style big band jazz
Favorite hobby: Swing dancing
If I weren’t a scientist I would be a: Chocolatier (see “Experiments in Chocolate” sidebar at bottom of story)

One day last fall, molecular biologist Laura Landweber Link to external web site surveyed the Princeton University lab where she’d worked for 22 years. She and her team members had spent many hours that day laboriously affixing yellow Post-it notes to the laboratory equipment—microscopes, centrifuges, computers—they would bring with them to Columbia University, where Landweber had just been appointed full professor. Each Post-it specified the machinery’s location in the new lab. Items that would be left behind—glassware, chemical solutions, furniture, office supplies—were left unlabeled.

As Landweber viewed the lab, decorated with a field of sunny squares, her thoughts turned to another sorting process—the one used by her primary research subject, a microscopic organism, to sift through excess DNA following mating. Rather than using Post-it notes, the creature, a type of single-celled organism called a ciliate, uses small pieces of RNA to tag which bits of genetic material to keep and which to toss.

Landweber is particularly fond of Oxytricha trifallax, a ciliate with relatives that live in soil, ponds and oceans all over the world. The kidney-shaped cell is covered with hair-like projections called cilia that help it move around and devour bacteria and algae. Oxytricha is not only bizarre in appearance, it’s also genetically creative.

Unlike humans, whose cells are programmed to die rather than pass on genomic errors, Oxytricha cells appear to delight in genomic chaos. During sexual reproduction, the ciliate shatters the DNA in one of its two nuclei into hundreds of thousands of pieces, descrambles the DNA letters, throws most away, then recombines the rest to create a new genome.

Landweber has set out to understand how—and possibly why—Oxytricha performs these unusual genomic acrobatics. Ultimately, she hopes that learning how Oxytricha rearranges its genome can illuminate some of the events that go awry during cancer, a disease in which the genome often suffers significant reorganization and damage.

Oxytricha’s Unique Features

Oxytricha carries two separate nuclei—a macronucleus and a micronucleus. The macronucleus, by far the larger of the two, functions like a typical genome, the source of gene transcription for proteins. The tiny micronucleus only sees action occasionally, when Oxytricha reproduces sexually.

Oxytricha trifallax cells in the process of mating
Two Oxytricha trifallax cells in the process of mating. Credit, Robert Hammersmith.

What really makes Oxytricha stand out is what it does with its DNA during the rare occasions that it has sex. When food is readily available, Oxytricha procreates without a partner, like a plant grown from a cutting. But when food is scarce, or the cell is stressed, it seeks a mate. When two Oxytricha cells mate, the micronuclear genomes in each cell swap DNA, then replicate. One copy of the new hybrid micronucleus remains intact, while the other breaks its DNA into hundreds of thousands of pieces, some of which are tagged, recombined, then copied another thousand-fold to form a new macronucleus. Continue reading

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

Interview With a Scientist: Janet Iwasa, Molecular Animator

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.

Interview With a Slime Mold: Racing for New Knowledge

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.

Credit: Daniel Irimia of Massachusetts General Hospital, and Monica Skoge and Albert Bae of the University of California, San Diego.

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 Exit icon 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

Visualizing Skin Regeneration in Real Time

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.

Another Piece to a Century-Old Evolutionary Puzzle

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 Exit icon 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

Cool Image: A Circadian Circuit

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

Seeing Telomerase’s ‘Whiskers’ and ‘Toes’

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

Interview With a Worm: We’re Not So Different

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