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  • richardmitnick 12:43 pm on January 28, 2020 Permalink | Reply
    Tags: "Hundreds of UCLA students publish paper analyzing 1000 genes involved in organ development", , , Genetics,   

    From UCLA Newsroom: “Hundreds of UCLA students publish paper analyzing 1,000 genes involved in organ development” 

    From UCLA Newsroom

    January 27, 2020
    Stuart Wolpert

    Visible on this page are images of fruit flies’ eyes (top), wings and lymph glands, showing which genes are active (red) or were previously active (green).

    A team of 245 UCLA undergraduates and 31 high school students has published an encyclopedia of more than 1,000 genes, including 421 genes whose functions were previously unknown. The research was conducted in fruit flies, and the genes the researchers describe in the analysis may be associated with the development of the brain, eye, lymph gland and wings.

    The fruit fly is often the object of scientific research because its cells have similar DNA to that of human cells — so knowledge about its genes can help researchers better understand human diseases. The UCLA study should be useful to scientists studying genes involved in sleep, vision, memory and many other processes in humans.

    The research is published in the journal G3: Genes, Genomes, Genetics. The study’s senior authors include researchers Cory Evans and John Olson, who taught UCLA’s Biomedical Research 10H, the course in which the studies were conducted.

    “I expect this will be a highly cited paper and a valuable resource to life scientists,” said Tracy Johnson, director of UCLA’s biomedical research minor, which offers the course the students all took. “It’s inspiring to know all of this really important research came from freshmen and sophomores. It’s beautiful, high-quality research.”

    The students studied short DNA sequences to learn how specific genes are turned on and off and understand how those genes control the functions of various cell types. Although all cells have essentially the same collection of genes, specific genes are turned on or off depending on the cells’ needs, Evans said.

    Each student studied several genes, ultimately producing a total of more than 50,000 microscopic images; the researchers then posted their analysis on an online database where other scientists can study the genes’ roles.

    “This shows not only which genes are turned on, but the history of which genes have been turned on,” Johnson said.

    The research was conducted as part of a UCLA life sciences course that was developed in the early 2000s by Utpal Banerjee, a UCLA distinguished professor of molecular, cell and developmental biology, a Howard Hughes Medical Institute Professor and a senior author of the paper. The course received initial funding from the HHMI.

    “Research on science education says that one of the best way to teach science is by having authentic research experiences embedded in a course,” said Johnson, who holds the Keith and Cecilia Terasaki Presidential Endowed Chair in the Division of Life Sciences and is an HHMI Professor. “Professor Banerjee understood years ago when he envisioned the class that students learn more by doing science. They learn how to design experiments, how to think like scientists, how to write about science and how to present their research.”

    Johnson said the approach is analogous to teaching a sport. “If a kid wants to play soccer, you don’t say, ‘Don’t touch the soccer ball yet. You have to first learn all of the rules, watch other people play and read about the soccer greats, and maybe in a couple of years, we’ll let you kick the ball.’ No, bring out the soccer balls! So we need to get science students in the lab.”

    The students completed two other research projects, one of which Evans expects will be published this year. In that study, the undergraduates studied the effects of turning off specific genes in fruit flies using a scientific technique called RNA interference. They then determined which of those 4,000 genes, when turned off, affect the proper development of blood cells.

    “We teach students how to do research, not fly biology,” said Evans, who is now an assistant professor of biology at Loyola Marymount University. “Their science literacy is high, and they know how to evaluate evidence.”

    See the full article here .

    Please help promote STEM in your local schools.

    Stem Education Coalition

    UC LA Campus

    For nearly 100 years, UCLA has been a pioneer, persevering through impossibility, turning the futile into the attainable.

    We doubt the critics, reject the status quo and see opportunity in dissatisfaction. Our campus, faculty and students are driven by optimism. It is not naïve; it is essential. And it has fueled every accomplishment, allowing us to redefine what’s possible, time after time.

    This can-do perspective has brought us 12 Nobel Prizes, 12 Rhodes Scholarships, more NCAA titles than any university and more Olympic medals than most nations. Our faculty and alumni helped create the Internet and pioneered reverse osmosis. And more than 100 companies have been created based on technology developed at UCLA.

  • richardmitnick 9:52 am on January 28, 2020 Permalink | Reply
    Tags: , , Genetics,   

    From UC Riverside: “Scientists short-circuit maturity in insects, opening new paths to disease prevention” 

    UC Riverside bloc

    From UC Riverside

    January 28, 2020
    Jules Bernstein

    Image shows the developing brain of an immature fruit fly. Green color shows the cell layer forming the blood-brain barrier, which physically separates the brain from the circulation. (Yamanaka/UCR)

    Puberty-controlling hormone does not travel freely into the brain as previously thought.

    New research from UC Riverside shows scientists may soon be able to prevent disease-spreading mosquitoes from maturing. Using the same gene-altering techniques, they may also be able help boost reproduction in beneficial bumblebees.

    The research shows that, contrary to previous scientific belief, a hormone required for sexual maturity in insects cannot travel across a mass of cells separating the blood from the brain — unless it is aided by a transporter protein molecule.

    “Before this finding, there had been a longstanding assumption that steroid hormones pass freely through the blood-brain barrier,” said Naoki Yamanaka, an assistant professor of entomology at UCR, who led the research. “We have shown that’s not so.”

    The study, published this month in the journal Current Biology, details the effects on sexual maturity in fruit flies when the transporter protein is blocked.

    Blocking the transporter not only prevented the steroid from entering the brain, it also permanently altered the flies’ behavior. When flies are in their infancy or “maggot” stage, they usually stay on or in a source of food.

    Later, as they prepare to enter a more adult phase of life, they exhibit “wandering behavior,” in which they come out of their food to find a place to shed their outer body layer and transform into an adult fly.

    When the transporter gene was blocked, Yamanaka said the flies entered a median stage between infancy and adulthood, but never wandered out of their food, and died slowly afterward without ever reaching adulthood or reproducing.

    “Our biggest motivation for this study was to challenge the prevailing assumption about free movement of steroids past the blood-brain barrier, by using fruit flies as a model species,” Yamanaka said. “In the long run, we’re interested in controlling the function of steroid hormone transporters to manipulate insect and potentially human behaviors.”

    Currently, Yamanaka is examining whether altering genes in mosquitoes could have a similar effect. Since mosquitoes are vectors for numerous diseases, including Zika, West Nile Virus, malaria and Dengue fever, there is great potential for the findings to improve human health.

    Conversely, there may be a way to alter the genes to manipulate reproduction in beneficial insects as well, in order to help them. Bumblebees, whose populations have been declining in recent years, pollinate many favorite human food crops.

    Also, there is the potential for this work to more directly impact humans. Steroid hormones affect a variety of behaviors and reactions in the human body. For example, the human body under stress makes a steroid hormone called cortisol. It enters the brain so humans can cope with the stressful situation.

    However, when chronic stress is experienced, cortisol can build up in the brain and cause multiple issues. “If the same machinery exists for cortisol in humans, we may be able to block the transporter in the blood-brain barrier to protect our brain from chronic stress,” Yamanaka said.

    “It’s an exciting finding,” said Yamanaka. “It was just in flies, but more than 70% of human disease-related genes have equivalents in flies, so there is a good chance this holds true for humans too.”

    See the full article here .


    Please help promote STEM in your local schools.

    Stem Education Coalition

    UC Riverside Campus

    The University of California, Riverside is one of 10 universities within the prestigious University of California system, and the only UC located in Inland Southern California.

    Widely recognized as one of the most ethnically diverse research universities in the nation, UCR’s current enrollment is more than 21,000 students, with a goal of 25,000 students by 2020. The campus is in the midst of a tremendous growth spurt with new and remodeled facilities coming on-line on a regular basis.

    We are located approximately 50 miles east of downtown Los Angeles. UCR is also within easy driving distance of dozens of major cultural and recreational sites, as well as desert, mountain and coastal destinations.

  • richardmitnick 11:56 am on December 8, 2019 Permalink | Reply
    Tags: , , , , Genetics, HSS-Smith; Hairston; and Slobodkin, , Robert Paine: "The Ecologist Who Threw Starfish", Sea otters, The HSS hypothesis was essentially a description of the natural world based on observation., There are ecological rules that regulate the numbers and kinds of animals and plants in a given place.   

    From Nautilus: “The Ecologist Who Threw Starfish” 


    From Nautilus

    March 10, 2016 [Just now in social media]
    By Sean B. Carroll
    Illustration by Aad Goudappel

    Illustration: Aad Goudappel

    Robert Paine showed us the surprising importance of predators.

    Even in 1963, one had to go pretty far to find places in the United States that were not disturbed by people. After a good deal of searching, Robert Paine, a newly appointed assistant professor of zoology at the University of Washington in Seattle, found a great prospect at the far northwestern corner of the lower 48 states.

    On a field trip with students to the Pacific Coast, Paine wound up at Mukkaw Bay, at the tip of the Olympic Peninsula. The curved bay’s sand and gravel beach faced west into the open ocean, and was dotted with large outcrops. Among the rocks, Paine discovered a thriving community. The tide pools were full of colorful creatures—green anemones, purple sea urchins, pink seaweed, bright red Pacific blood starfish, as well as sponges, limpets, and chitons. Along the rock faces, the low tide exposed bands of small acorn barnacles, and large, stalked goose barnacles, beds of black California mussels, and some very large, purple and orange starfish, called Pisaster ochraceus.

    “Wow, this is what I have been looking for,” he thought.

    Star hurler: Robert Paine at Mukkaw Bay, on the Olympic Peninsula in Washington, in 1974, and again recently. To understand the role of predatory starfish he hurled them from an area and later returned to assess the sea life without them.
    Left: Bob Paine / Alamy.com ; Right: Kevin Schafer / Alamy Stock Photo

    The next month, June 1963, he made the four-hour journey back to Mukkaw from Seattle, first crossing Puget Sound by ferry, then driving along the coastline of the Straits of Juan de Fuca, then onto the lands of the Makah Nation, and out to the cove of Mukkaw Bay. At low tide, he scampered onto a rocky outcrop.

    With a crowbar in hand and mustering all of the leverage he could with his 6-foot, 6-inch frame, he pried loose every purple or orange starfish on the slab, grabbed them, and hurled them as far as he could out into the bay.

    So began one of the most important experiments in the history of ecology.

    The 1960s were a time of revolution, but it was not all just sex, drugs, and rock and roll. Inside laboratories across the world, scientists were plumbing the depths of the gene to decipher the genetic code and the molecular rules of life, sparking a revolution that would gather dozens of Nobel Prizes and ultimately transform medicine.

    But largely outside of this spotlight, a few other biologists had started asking some simple, seemingly naïve questions about the wider world: Why is the planet green? Why don’t the animals eat all of the food? And what happens when certain animals are removed from a place? These questions led to the discovery that, just as there are molecular rules that regulate the numbers of different kinds of molecules and cells in the body, there are ecological rules that regulate the numbers and kinds of animals and plants in a given place. And these rules may have as much or more to do with our future welfare than all the molecular rules we may ever discover.

    Why Is the Planet Green?

    Paine’s journey to Mukkaw Bay and its starfish was a circuitous one. Born and raised in Cambridge, Massachusetts, Paine’s interests in nature were fueled by exploring the New England woods. His first love was bird-watching, with butterflies and salamanders close seconds. Paine was inspired by the writings of prominent naturalists, who opened his eyes to the drama of wildlife. He was as enthralled by intimate accounts of spider behavior as by Jim Corbett’s hair-raising tales of tracking down tigers and leopards in rural India, in Man-Eaters of Kumaon.

    After enrolling at Harvard, and inspired by several famous paleontologists on the faculty, Paine developed an intense new interest in animal fossils. He was so fascinated by the marine animals that lived in the seas more than 400 million years ago that he decided to study geology and paleontology in graduate school at the University of Michigan.

    The course requirements entailed rather dry surveys of various animal “ologies”—ichthyology (fishes), herpetology (reptiles and amphibians), and so forth that Paine found very boring. One exception was a course on the natural history of freshwater invertebrates taught by ecologist Fred Smith. Paine appreciated how the professor provoked his students to think.

    One memorable spring day, the sort of day when professors don’t feel like teaching and students don’t want to be inside, Smith told the class, “We are going to stay in this room.” He looked outside at a tree that was just getting its leaves.

“Why is that tree green?” Smith asked, looking out the window.

    “Chlorophyll,” a student replied, correctly naming the leaf pigment, but Smith was heading down a different path.

    “Why isn’t all of its greenery eaten?” Smith continued. It was such a simple question, but Smith showed how even such basic things were not known. “There is a host of insects out there. Maybe something is controlling them?” he mused.

    At the end of his first year, Smith sensed Paine’s unhappiness with geology, and suggested that he consider ecology instead. “Why don’t you be my student?” he asked.

    It was a major change in direction, and there was a catch. Paine proposed to study some fossil animals from the Devonian period in nearby rocks. Smith said, “No way.” Paine had to study living, not extinct creatures. Paine agreed, and Smith became his adviser.

    Smith had long been interested in brachiopods or “lamp shells,” marine animals with an upper and lower shell, joined at a hinge. Paine knew about the animals because they were abundant in the fossil record, but their present-day ecology was not well known. Paine’s first task was to find living forms. Lacking a nearby ocean, Paine made scouting trips to Florida in 1957 and 1958, and found some promising locations. With Smith’s approval, he began what he called his “graduate-student sabbatical.” In June 1959, he drove back to Florida and began living out of his Volkswagen van. For 11 months he studied the range, habitat, and behavior of one species.

    It was the sort of work that provided a solid foundation to a naturalist-in-training, and it would earn Paine his Ph.D. But the filter-feeding brachiopods were not the most dynamic animals. And sifting large amounts of sand for the less than quarter-inch-long creatures was, well, just not very exciting.

    As Paine shoveled his way along the Gulf Coast, it was not Florida’s brachiopods that captured his imagination. On the Florida panhandle, Paine discovered the Alligator Harbor Marine Laboratory, and was given permission to stay there. At the tip of nearby Alligator Point, he noticed that for a few days each month, the low tide exposed an enormous gathering of large predatory snails, such as the horse conch, some more than a foot long. The mud and sawgrass of Alligator Point was not at all boring, quite the contrary—it was a battlefield.

    On top of his thesis work on brachiopods, Paine made a careful study of the snails. He counted eight abundant snail species, and took detailed notes on who ate whom. In this “gastropod eats gastropod” arena, Paine saw that without exception it was always a larger snail devouring a smaller one, but not everything that was smaller. The 11-pound horse conch, for example, dined almost exclusively on other snails, and paid little attention to smaller prey such as the clams that were the main fare for the smaller snails.

    While Paine was in Florida watching predators up close, his advisor Smith had kept thinking about those green trees and the roles of predators in nature. Smith was keenly interested in not just the structure of communities, but in the processes that shaped them. He often had bag lunches with two colleagues, Nelson Hairston Sr. and Lawrence Slobodkin, during which they had friendly arguments about major ideas in ecology. All three scientists were interested in the processes that control animal populations, and they debated explanations circulating at the time. One major school of thought was that population size was controlled by physical conditions such as the weather. Smith, Hairston, and Slobodkin (hereafter dubbed “HSS”) all doubted this idea because, if true, it meant that population sizes fluctuated randomly with the weather. Instead, the trio was convinced that biological processes must control the abundance of species in nature, at least to some degree.

    HSS pictured the food chain as subdivided into different levels according to the food each consumed (known as trophic levels). At the bottom were the decomposers that degrade organic debris; above them were the producers, the plants that relied on sunlight, rain, and soil nutrients; the next level were the consumers, the herbivores that ate plants; and above them the predators that ate the herbivores.

    The ecological community generally accepted that each level limited the next higher level; that is, populations were positively regulated from the “bottom up.” But Smith and his lunch buddies pondered the observation that seemed at odds with this view: The terrestrial world is green. They knew that herbivores generally do not completely consume all of the vegetation available. Indeed, most plant leaves only show signs of being partially eaten. To HSS, that meant that herbivores were not food-limited, and that something else was limiting herbivore populations. That something, they believed, were predators, negatively regulating herbivore populations from the “top-down” in the food chain. While predator-prey relationships had long been studied by ecologists, it was generally thought that the availability of prey regulated predator numbers and not vice-versa. The proposal that predators as a whole acted to regulate prey populations was a radical twist.

    To bolster their case, HSS noted instances where herbivore populations had exploded after the removal of predators, such as the Kaibab deer population in Northern Arizona that increased after decimation of local wolf and coyote populations. They assembled their observations and arguments in a paper entitled “Community Structure, Population Control, and Competition” and submitted it to the journal Ecology in May 1959.

    It was rejected. The article did not see the light of day until the year-end issue of the American Naturalist in 1960.

    The proposal that predators regulate herbivore populations is now widely known as the “HSS hypothesis” or “Green World Hypothesis.” While HSS declared, “The logic used is not easily refuted,” their ideas, like most that challenge the status quo, drew a lot of criticism. One legitimate critique was their claims needed testing and more evidence. And that was just what Smith’s former student set out to do on Mukkaw Bay in 1963.

    Ruler of the tidal zone: Starfish are opportunistic gourmands that eat barnacles, limpets, snails, and mussels. In this rocky intertidal zone on the Pacific coast, the starfish prey on mussels, which enables other species such as kelp and small animals to occupy the community. David Cowles, rosario.wallawalla.edu/inverts

    Kick It and See

    The HSS hypothesis was essentially a description of the natural world based on observation. Indeed, virtually all of ecology up to the 1960s had been based upon observation. The limitation of such observational biology was that it left itself open to alternative explanations and hypotheses. Paine realized that if he wanted to understand how nature worked—the rules that regulated animal populations—he would have to find situations where he could intervene and break them. In the specific case of the roles of predators, he needed a setting where he could remove predators and see what happened—what would later be described as “kick it and see” ecology. Hence, the starfish-hurling.

    Twice a month every spring and summer, and once a month in the winter, Paine kept returning to Mukkaw to repeat his starfish-throwing ritual. On a 25-feet long, 6-feet tall stretch of rock, he removed all of the starfish. On an adjacent stretch, he let nature take her course. On each plot, he counted the number and calculated the density of the inhabitants, tracking 15 species in all.

    To understand the structure of the Mukkaw food web, Paine paid close attention to what the predators were eating. The starfish has the neat trick of everting its stomach to consume prey. To see what they were feasting upon, Paine turned more than 1,000 starfish over and examined the animals held against their stomachs. He discovered that the starfish was an opportunistic gourmand that ate barnacles, chitons, limpets, snails, and mussels. While the small barnacles were the most numerous prey—the starfish was able to scarf up dozens of the little crustaceans at a time—they were not its primary source of calories. Mussels and chitons were the most important contributors to the starfish diet.

    By September, just three months after he began removing the starfish, Paine could already see that the community was changing. The acorn barnacles had spread out to occupy 60 to 80 percent of the available space. But by June of 1964, a year into the experiment, the acorn barnacles were in turn being crowded out by small, but rapidly growing goose barnacles and mussels. Moreover, four species of algae had largely disappeared, and the two limpet and two chiton species had abandoned the plot. While not preyed upon by the starfish, the anemone and sponges populations had also decreased. However, the population of one small predatory snail, Thais emarginata, increased 10- to 20-fold.

    Altogether, the removal of the predatory starfish had quickly reduced the diversity of the intertidal community from the original 15 species to eight.

    The results of this simple experiment were astonishing. They showed that one predator could control the composition of species in a community through its prey—affecting both animals it ate as well as animals and plants that it did not eat.

    As Paine continued the experiment over the next five years, the line of mussels advanced down the rock face by an average of almost 3 feet toward the low tide mark, monopolizing most of the available space and pushing all other species out completely. Paine realized that the starfish exerted their strong effects primarily by keeping the mussels in check. For the animals and algae of the intertidal zone, the important resource was real estate—space on the rocks. The mussels were very strong competitors for that space, and without the starfish, they took over and forced other species out. The predator stabilized the community by negatively regulating the population of the competitively dominant species.

    Paine’s starfish-tossing was strong confirmation of the HSS hypothesis that predators exerted control from the top down. But this was just one experiment with one predator in one spot on the Pacific Coast. If Paine was going to draw any generalities, it was important to test other sites and other predators. The dramatic results of the Mukkaw Bay experiments inspired a flurry of kick-it-and-see experiments.

    Paine discovered uninhabited Tatoosh Island when he was out on a salmon-fishing trip. On this small, storm-battered island, several miles up the coast from Mukkaw Bay and about half a mile offshore, Paine found many of the same species clinging to the rocks, including large Pisaster starfish. With the permission of the Makah tribe, Paine started tossing them back in the water. Within a few months, the mussels started spreading across the predator-free rocks.

    While on sabbatical in New Zealand, Paine investigated another intertidal community at the north end of a beach near Auckland. There, he found a different starfish species called Stichaster australis that preyed on the New Zealand green-lipped mussel, the same species exported to restaurants around the world. Over a period of nine months Paine removed all of the starfish from one 400-square-foot area, and left an adjacent, similar plot alone. He saw immediate and striking effects. The treated area quickly began to be dominated by mussels. Six of 20 other species initially present vanished in just eight months; within 15 months the majority of space was occupied solely by the mussels.

    To Paine, the predatory starfish of Washington and New Zealand were “keystones” in the structure of intertidal communities. Just as the stone at the apex of an arch is necessary for the stability of the structure, these apex predators at the top of the food web are critical to the diversity of an ecosystem. Dislodge them, and as Paine showed, the community falls apart. Paine’s pioneering experiments, and his coining of the term “keystone species” prompted the search for keystones in other communities, and would lead him to another seminal idea.

    Sea Otters and the Cascading Effect

    Paine’s kick-it-and-see experiments were not limited to manipulating predators. He was interested in understanding the rules that determined the overall make-up of coastal communities. Other prominent inhabitants of the tide pools and shallow waters included a great variety of algae, such as the large brown seaweed known as kelp. But their distribution was patchy—abundant and diverse in some places, nearly absent from others. One of the most prevalent grazers on the algae were sea urchins. Paine and zoologist Robert Vadas set out to find out what effect the urchins had on algal diversity.

    To do so, they removed all of the urchins by hand from some pools around Mukkaw Bay, or barred them from areas within Friday Harbor (near Bellingham) with wire cages. They left nearby pools and areas untouched as controls for their experiment. They observed dramatic effects of removing the sea urchins—several species of algae burst forth in the urchin-free zones. The control areas with large urchin populations contained very few algae.

    Paine also noticed that such urchin-dominated “barrens” were common in pools around Tatoosh Island. At first glance, the urchin barrens seemed to violate a key assertion of the HSS hypothesis that herbivores tended not to consume all of the vegetation available. But the explanation for why there were such barrens in Pacific waters would soon become clear—in the surprising discovery of another keystone species, an animal that had been removed from Washington’s coast long before Paine started tinkering with nature.

    Sea otters once ranged from Northern Japan to the Aleutian Islands and along the North American Pacific Coast as far south as Baja California. Coveted for their luxurious fur, the densest of all marine mammals, the animals were hunted so intensively in the 18th and 19th centuries that by the early 1900s only 2,000 or so animals remained of an original population of 150,000 to 300,000, and the species had disappeared from most of its range, including Washington state. The species gained protected status in 1911 under the terms of an international treaty. After their near-extermination from the Aleutian Islands, the animals rebounded to high densities in some locations.

    In 1971, Paine was offered a trip to one of those places—Amchitka Island, a treeless island in the western part of the Aleutians. Some students were working on the kelp communities there and Paine flew out to offer his advice. Jim Estes, a student from the University of Arizona, met with Paine and described his research plans. Estes was interested in sea otters, but he was not an ecologist. He explained to Paine that he was thinking about studying how the kelp forests supported the thriving sea otter populations.

    “Jim, you are asking the wrong questions,” Paine told him. “You want to look at the three trophic levels: sea otters eat urchins, sea urchins eat kelp.”

    The importance of being a sea otter: In the presence of sea otters, sea urchin populations are controlled, which allows for kelp forests to grow (left). In the absence of sea otters, urchins proliferate, forming “barrens” that lack kelp (right). Bob Steneck

    Estes had only seen Amchitka with its abundant otters and kelp forests. He quickly realized the opportunity to compare islands with and without otters. With fellow student John Palmisano, Estes traveled to Shemya Island, a 6-square-mile chunk of rock 200 miles to the west without otters. Their first hint that something was very different was when they walked down to the beach and saw huge sea urchin carcasses. But the real shock came when Estes dove under the water for the first time.

    “The most dramatic moment of learning in my life happened in less than a second. And that was sticking my head in the water at Shemya Island,” Estes recalled. “We were in this sea of just sea urchins. And there was no kelp anywhere. Any fool would have been able to figure out what was going on.”

    Estes and Palmisano saw other striking differences between the two communities around each island: Colorful rockfish, harbor seals, and bald eagles were abundant around Amchitka, but not around otter-less Shemya. They proposed that the vast differences between the two communities were driven by sea otters, which were voracious predators of sea urchins. They suggested that sea otters were keystone species whose negative regulation of sea urchin populations was key to the structure and diversity of the coastal marine community.

    Estes’ and Palmisano’s observations suggested that the reintroduction of sea otters would lead to a dramatic restructuring of coastal ecosystems. Shortly after their pioneering study, the opportunity arose to test the impact of sea otters as they spread along the Alaskan coast and re-colonized various communities. In 1975, sea otters were absent from Deer Harbor in southeast Alaska. But by 1978, the animals had established themselves there, sea urchins were small and scarce, the sea bottom was littered with their remains, and tall, dense stands of kelp had sprung up.

    The presence of the otters had suppressed the urchins, which had otherwise suppressed the growth of kelp. This kind of double negative logic is widespread in biology. In this instance, otters “induce” the growth of kelp by repressing the population of sea urchins. The discovery of the regulation of kelp forest by sea otter predation on herbivorous urchins was very strong support for the HSS hypothesis and for Paine’s keystone species concept.

    In ecological terms, the predatory sea otters have a cascading effect on multiple trophic levels below them. Paine coined a new term to describe the strong, top-down effects that he and others had discovered upon the removal or reintroduction of species: He called them trophic cascades.

    The discovery of trophic cascades was exciting. The many indirect effects caused by the presence or absence of predators (starfish, sea otters) were surprising because they revealed previously unsuspected, indeed unimagined, connections among creatures. Who would have thought that the growth of kelp forests depended on the presence of sea otters? These dramatic and unexpected effects raised the possibility that, unbeknownst to biologists, trophic cascades were operating elsewhere to shape other kinds of communities. And if they were, then keystone species and trophic cascades might be general features of ecosystems—rules of regulation that governed the numbers and kinds of creatures in a community.

    Indeed, trophic cascades have been discovered across the globe, where keystone predators such as wolves, lions, sharks, coyotes, starfish, and spiders shape communities. And because of their newly appreciated regulatory roles, the loss of large predators over the past century has Estes, Paine, and many other biologists deeply concerned.

    Today, of course, one predator has more influence than any other. We have created the extraordinary ecological situation where we are the top predator and the top consumer in all habitats. “Humans are certainly the overdominant keystones and will be the ultimate losers if the rules are not understood and global ecosystems continue to deteriorate,” Paine says. The only species that can regulate us is us.

    See the full article here .

    Lauren Eiseley has a story of another starthrower (The Starthrower, Harcourt BraceJanovich, 1978, ©Estate of Loren C. Eiseley, pg 169. “The Starthrower”, a man (unnamed) who said he threw the starfish back because one never knew where the next important DNA might originate.


    Please help promote STEM in your local schools.

    Stem Education Coalition

    Welcome to Nautilus. We are delighted you joined us. We are here to tell you about science and its endless connections to our lives. Each month we choose a single topic. And each Thursday we publish a new chapter on that topic online. Each issue combines the sciences, culture and philosophy into a single story told by the world’s leading thinkers and writers. We follow the story wherever it leads us. Read our essays, investigative reports, and blogs. Fiction, too. Take in our games, videos, and graphic stories. Stop in for a minute, or an hour. Nautilus lets science spill over its usual borders. We are science, connected.

  • richardmitnick 8:26 am on September 18, 2019 Permalink | Reply
    Tags: "Dark DNA Is the Genetic Code That Should Be There but Isn't", , , , , Genetics   

    From Curiosity: “Dark DNA Is the Genetic Code That Should Be There, but Isn’t” 

    Curiosity Makes You Smarter

    From From Curiosity

    September 16, 2017
    Reuben Westmaas


    You may have heard of “dark matter” — the mysterious stuff that apparently makes up 27 percent of the universe but can’t be detected by conventional means. But we don’t have to look deep into outer space to find an intractable mystery. “Dark DNA” is the biological cousin of dark matter, in the sense that we can’t see it but we know it’s there. And hiding with it just might be some of evolution’s deepest secrets.


    The more scientists map the genome, the more they come to understand exactly how gene sequences are reflected in the fully formed animal. We’ve come to understand why giraffes are so tall, why snakes are so long, and soon, we’ll probably find the gene that explains why some people don’t like “Game of Thrones.” But every once in a while, armed with the knowledge of what genes do what, we’ll go searching for something we know is there, and come up empty-handed.

    In a piece published on The Conversation, evolutionary biologist Adam Hargreaves describes hitting such an obstacle while researching the sand rat, a species of gerbil that’s much cuter than its name implies.

    The adorable, unfairly named sand rat

    These little furballs are particularly prone to type-2 diabetes, so Hargreaves and his colleagues sought to explain the phenomenon by examining a gene called Pdx1, which governs the production of insulin. But it wasn’t there. And neither were the 87 other genes that surround it.

    The thing is, we know for a fact that the sand rat has the gene Pdx1 since it’s absolutely necessary for survival. What’s more, plenty of the other 87 missing genes are just as necessary. Just to make sure, Hargreaves and company looked for certain chemical compounds in the sand rat’s muscle tissues that would have been produced by the missing genes — and sure enough, there they were. But why weren’t the genes where they were supposed to be? And where were they really?

    By the way, sand rats aren’t the only animals to have misplaced genes. Actually, well over 200 genes have yet to be discovered in birds, but we know for a fact that they must be in there somewhere. Pdx1 and its surrounding genes, as well the missing bird genes, are all rich in G and C molecules, which have historically been difficult for gene-sequencing technology to detect. So since they aren’t turning up where we expect them, they’ve managed to slip our attention like a needle in a haystack.

    The Evolution Will Not Be Gene Sequenced

    There was another little surprise that turned up in the gene-sequencing of the sand rat. One section of their genome seemed to be much more likely to mutate than any other part — a section that was rife with G and C molecules. So it’s probably not a huge stretch of the imagination to guess that the missing genes are somewhere in that section, even if our modern gene-sequencing technology isn’t especially great at identifying them yet.

    So the thing is, those “mutation hotspots” could be one of the key ingredients in evolution itself. Evolution, obviously, depends on mutation in order to progress. Once a trait emerges, natural selection determines if it is a good idea or not, which just a fancy way of saying that if the mutation hurts the animal, it’s less likely to live long enough to pass it on. Conversely, if the mutation helps the animal, it will have all the time in the world to have tons of babies with very similar genes.

    In the case of the sand rat, the mutation hotspot that likely governs insulin production and other traits may have provided the key to its survival in the harsh desert landscape. But even as those mutations help the animal in some ways, they could hurt it in others — it’s just that, for now, the good parts outweigh the bad. If the environment changes to the point that desert adaptation isn’t so important anymore, then it’s likely that the sand rat’s poor insulin regulation will start to weigh heavier on its success story.

    See the full article here .


    Please help promote STEM in your local schools.

    Stem Education Coalition

    Curiosity Makes You Smarter

    Curiosity is on a mission to make learning easier and more fun than it has ever been. Our goal is to ignite curiosity and inspire people to learn. Each day, we create and curate engaging topics for millions of lifelong learners worldwide.

    Experience Curiosity on our website, through our apps and across social media. We designed Curiosity with your busy life in mind. Our editors find interesting and important topics that you’ll want to know more about, and introduce you to the best ways to keep learning.

    We hope you make Curiosity part of your daily digital diet. Never stop learning!

  • richardmitnick 7:26 am on September 4, 2018 Permalink | Reply
    Tags: , Biobank, Biostatistics, Genetics, GenV, Integrated healthcare data, Karen Lamb,   

    From COSMOS Magazine: Women in STEM- “Superstars of STEM: Finding the trends in newborn lives” Karen Lamb. 

    Cosmos Magazine bloc

    From COSMOS Magazine

    04 September 2018
    Dion Pretorius

    Biostatistician Karen Lamb. Credit STA

    The world is on the cusp of a digital health transformation, and integrated healthcare data is already enhancing the way people access care, tackle disease and respond to treatments.

    New technology is allowing healthcare professionals to begin personalising medicines, as well as informing much more sophisticated research. As a result, we are beginning to better understand how and why people respond differently to the same treatment or drug.

    But there is the potential to do so much more.

    Karen Lamb is a senior team member at GenV (Generation Victoria), a project led by the Murdoch Children’s Research Institute (MCRI) in the Australian city of Melbourne.

    GenV plans to approach all babies born in the state of Victoria in 2020, and follow them for two years, asking their parents’ consent to take part throughout the baby’s childhood. It will put the state’s medical research at the forefront of this data revolution.

    Lamb is a biostatistician, brought in to make sure the data from this world-first project is as accessible and useful for researchers as possible.

    She says that the project is unique in the way it focusses on an entire population of newborns within a state or territory, rather than just a sample – which makes it one of the most ambitious children’s projects ever attempted.

    The team is looking to amalgamate data that is already collected and stored separately during routine check-ups, to inform future research. For interested families, they also plan to collect additional genetic information from the children and their parents.

    “Each person’s information is unique, but combine data from a large population and you can unravel valuable trends and patterns,” Lamb explains.

    “By improving, combining and unifying the data, researchers will be able to do things like identify markers for disease; trends in obesity and cardiovascular disease; devise ways to diagnose and treat allergies; and provide a foundation for better integrated health data across Victoria.”

    Melissa Wake, director of GenV, says that by 2035 the project’s mission is to have solved complex health, development and wellbeing issues for children now, and the adults they will become.

    Wake says to create a study of this scale, the team looked at examples from overseas, such as the UK Biobank, the Norwegian Mother and Child Cohort Study, and the Japan Environment and Children’s Study.

    “In the UK, their Biobank work has uncovered genes associated with Alzheimer’s disease and helped researchers to map genetic variants that increase the risk of depression,” Wake says.

    Lamb says that expertise in biostatistics has been shown to be critical in assisting in the design of studies and in developing methodologies to tackle complex health questions.

    “I can ensure that the data is protected, de-identified, and stored in a way that is easily accessible and relevant for researchers,” she says.

    “This means scientists will be spending less time collecting, cleaning and refining data sets, and more time working on treatments for some of the world’s most challenging diseases. In addition, families will know that their data are not only safe and private, but helping other children in the future.”

    See the full article here .

    Please help promote STEM in your local schools.

    Stem Education Coalition

  • richardmitnick 12:24 am on July 2, 2018 Permalink | Reply
    Tags: , C6orf106 or "C6", , , , Gene discovery unlocks mysteries of our immunity, Genetics, Our immune system   

    From Commonwealth Scientific and Industrial Research Organisation CSIRO: “Gene discovery unlocks mysteries of our immunity” 

    CSIRO bloc

    From Commonwealth Scientific and Industrial Research Organisation CSIRO


    Ofa Fitzgibbons
    Communication Advisor
    +61 2 4960 6188

    Australia’s national science agency CSIRO has identified a new gene that plays a critical role in regulating the body’s immune response to infection and disease.

    The C6orf106 or “C6” gene. No image credit.

    The discovery could lead to the development of new treatments for influenza, arthritis and even cancer.

    The gene, called C6orf106 or “C6”, controls the production of proteins involved in infectious diseases, cancer and diabetes. The gene has existed for 500 million years, but its potential is only now understood.

    “Our immune system produces proteins called cytokines that help fortify the immune system and work to prevent viruses and other pathogens from replicating and causing disease,” CSIRO researcher Dr Cameron Stewart said.

    “C6 regulates this process by switching off the production of certain cytokines to stop our immune response from spiralling out of control.

    “The cytokines regulated by C6 are implicated in a variety of diseases including cancer, diabetes and inflammatory disorders such as rheumatoid arthritis.”

    The discovery helps improve our understanding of our immune system, and it is hoped that this understanding will enable scientists to develop new, more targeted therapies.

    Dr Rebecca Ambrose was part of the CSIRO team that discovered the gene, and co-authored the recent paper announcing the discovery in the Journal of Biological Chemistry.

    “Even though the human genome was first fully sequenced in 2003, there are still thousands of genes that we know very little about,” Dr Rebecca Ambrose, a former CSIRO researcher, now based at the Hudson Institute of Medical Research said.

    “It’s exciting to consider that C6 has existed for more than 500 million years, preserved and passed down from simple organisms all the way to humans. But only now are we gaining insights into its importance.”

    Having discovered the function of C6, the researchers are awarded the privilege of naming it, and are enlisting the help of the community to do so.

    “The current name, C6orf106, reflects the gene’s location within the human genome, rather than relating to any particular function,” Dr Stewart said.

    “We think we can do better than that, and are inviting suggestions from the public.”

    A shortlist of names will be made available for final approval by a governing third party.

    The breakthrough builds on decades of work in infectious diseases, by researchers from CSIRO, Australia’s national science agency.

    See the full article here .


    Please help promote STEM in your local schools.

    Stem Education Coalition

    CSIRO campus

    CSIRO, the Commonwealth Scientific and Industrial Research Organisation, is Australia’s national science agency and one of the largest and most diverse research agencies in the world.

  • richardmitnick 1:49 pm on June 29, 2018 Permalink | Reply
    Tags: ADA-SCID or bubble baby disease, Family travels 7500 miles to save son’s life with treatment developed at UCLA, Genetics, ,   

    From UCLA Newsroom: “Family travels 7,500 miles to save son’s life with treatment developed at UCLA” 

    From UCLA Newsroom

    June 28, 2018
    Mirabai Vogt-James

    Stem cell gene therapy cures baby with life-threatening immune disorder.

    Hussein El Kerdi before and after his successful treatment for ADA-SCID, also known as bubble baby disease. Courtesy of the El Kerdi family.

    When he was born in September 2015, Hussein El Kerdi looked like a healthy baby boy. No one knew that his immune cells lacked an important enzyme. But the absence of that enzyme would profoundly change the El Kerdi family’s life, sending them on a journey from their small hometown in Lebanon to UCLA. Their one goal: to save Hussein’s life.

    When Hussein was three months old, a physician in Beirut diagnosed Hussein with a life-threatening immune disorder called adenosine deaminase-deficient severe combined immunodeficiency, also known as ADA-SCID or bubble baby disease.

    The disorder is caused by a genetic mutation that results in lack of the adenosine deaminase enzyme, without which immune cells cannot fight infections. Babies with the disease must remain isolated in germ-free environments to avoid exposure to viruses and bacteria. If the disease is not treated, even a minor cold could be fatal, and babies with the condition typically do not survive past their second birthday.

    Dr. Donald Kohn, a physician-scientist at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, has been perfecting a stem cell gene therapy for bubble baby disease for more than three decades. The treatment uses blood-forming stem cells, which have two important properties: They can make exact copies of themselves and they can produce all of the cells that make up the blood system, including immune cells such as T cells.

    Kohn’s treatment involves removing those blood-forming stem cells from the patient’s bone marrow and correcting the genetic mutation by inserting the gene responsible for making adenosine deaminase. The corrected stem cells are then infused back into the patient, where they begin producing a continual supply of healthy immune cells that are capable of fighting infection.

    Kohn, whose work focuses on genetic blood disorders, received approval from the U.S. Food and Drug Administration in 1993 to test the treatment in clinical trials. Since then, 30 out of 30 babies with the condition have been cured in six trials run by Kohn; data from a seventh trial is currently being analyzed.

    2017 study analyzes therapy for bubble baby disease

    In Lebanon, Hussein’s father, Ali, and mother, Zahraa, had heard nothing about the treatment. They were told that there had been no other cases of bubble baby disease in the Middle East, and that Great Britain and the U.S. were the only places where this experimental treatment was available.

    With help from family and friends, the El Kerdis created a plan that would eventually bring them to UCLA. A relative who is a doctor in Michigan emailed Kohn to tell him about Hussein, and Kohn — along with colleagues from the UCLA Broad Stem Cell Research Center, the David Geffen School of Medicine at UCLA and UCLA Mattel Children’s Hospital — began to make arrangements for the El Kerdis’ arrival and Hussein’s treatment.

    In April 2016, the family arrived in Los Angeles; Hussein was six months old and desperately ill.

    “I hadn’t seen a patient like Hussein in 15 or 20 years,” Kohn said. “About three to four weeks in, I thought he wasn’t going to make it through. But he did.”

    Each day leading up to his stem cell gene therapy treatment, Hussein became stronger thanks to the expert care provided by the pediatric intensive care unit at the children’s hospital.

    On July 12, 2016, some of Hussein’s bone marrow was removed and blood-forming stem cells were extracted from it. Two days later, after the cells were genetically modified, they were infused back into Hussein. Over the next couple of months, the stem cells began to create immune cells that produce adenosine deaminase. By the beginning of that September, just a few weeks before his first birthday, Hussein was healthy enough to go home.

    Evangelina’s story: Another baby with the condition is cured

    Before leaving UCLA, the El Kerdis celebrated Hussein’s birthday with Kohn and several of the nurses who cared for him. During the celebration, Ali and Zahraa expressed their gratitude.

    Hussein El Kerdi during his 2016 procedure at UCLA. His father, Ali El Kerdi (with cell phone) looks on. UCLA Broad Stem Cell Research Center.

    “I hope that when Hussein grows up, he comes to the States and gets educated to be a doctor at UCLA,” Ali El Kerdi said. “On behalf of myself and my wife and child, I want to say thank you to Dr. Kohn and to UCLA and to all the people who helped bring this miracle to life.”

    Zahraa El Kerdi said, “I cannot describe my happiness; I’m going back to my family with my child in good health. It’s so exciting, I cannot describe it.”

    Now, nearly two years after the procedure, Hussein is healthy and thriving at home with his family.

    Orchard Therapeutics, a biotechnology company that was launched in 2016, is working to bring the therapy that Hussein received to more patients.

    $20 million grant funds new clinical trial on ADA-SCID

    The company has a research partnership with UCLA to develop the treatment that Kohn created as a frozen product, which would allow it to be used at other medical centers. Kohn is hopeful that the treatment, called OTL-101, will be approved by the FDA in due course so that it can be made available to hospitals across the U.S.

    Kohn is currently conducting clinical trials that test similar stem cell gene therapy techniques for other blood diseases, including sickle cell disease, which is the most common inherited blood disorder in the U.S.

    Kohn is a paid member of the Orchard Therapeutics scientific advisory board; on behalf of the Regents of the University of California, the UCLA Technology Development Group has licensed intellectual property related to the ADA-SCID treatment developed by Kohn to the company.

    See the full article here .

    Please help promote STEM in your local schools.

    Stem Education Coalition

    UC LA Campus

    For nearly 100 years, UCLA has been a pioneer, persevering through impossibility, turning the futile into the attainable.

    We doubt the critics, reject the status quo and see opportunity in dissatisfaction. Our campus, faculty and students are driven by optimism. It is not naïve; it is essential. And it has fueled every accomplishment, allowing us to redefine what’s possible, time after time.

    This can-do perspective has brought us 12 Nobel Prizes, 12 Rhodes Scholarships, more NCAA titles than any university and more Olympic medals than most nations. Our faculty and alumni helped create the Internet and pioneered reverse osmosis. And more than 100 companies have been created based on technology developed at UCLA.

  • richardmitnick 1:13 pm on June 18, 2018 Permalink | Reply
    Tags: , Genetics, , ,   

    From Lawrence Berkeley National Lab: “Faster, Cheaper, Better: A New Way to Synthesize DNA” 

    Berkeley Logo

    From Lawrence Berkeley National Lab

    June 18, 2018
    Julie Chao
    (510) 486-6491

    Sebastian Palluk (left) and Daniel Arlow of the Joint BioEnergy Institute (JBEI) have pioneered a new way to synthesize DNA sequences. (Credit: Marilyn Chung/Berkeley Lab)

    In the rapidly growing field of synthetic biology, in which organisms can be engineered to do things like decompose plastic and manufacture biofuels and medicines, production of custom DNA sequences is a fundamental tool for scientific discovery. Yet the process of DNA synthesis, which has remained virtually unchanged for more than 40 years, can be slow and unreliable.

    Now in what could address a critical bottleneck in biology research, researchers at the Department of Energy’s Joint BioEnergy Institute (JBEI), based at Lawrence Berkeley National Laboratory (Berkeley Lab), announced they have pioneered a new way to synthesize DNA sequences through a creative use of enzymes that promises to be faster, cheaper, and more accurate. The discovery, led by JBEI graduate students Sebastian Palluk and Daniel Arlow, was published in Nature Biotechnology in a paper titled De novo DNA Synthesis Using Polymerase-Nucleotide Conjugates.

    “DNA synthesis is at the core of everything we try to do when we build biology,” said JBEI CEO Jay Keasling, the corresponding author on the paper and also a Berkeley Lab senior faculty scientist. “Sebastian and Dan have created what I think will be the best way to synthesize DNA since [Marvin] Caruthers invented solid-phase DNA synthesis almost 40 years ago. What this means for science is that we can engineer biology much less expensively – and in new ways – than we would have been able to do in the past.”

    The Caruthers process uses the tools of organic chemistry to attach DNA building blocks one at a time and has become the standard method used by DNA synthesis companies and labs around the world. However, it has drawbacks, the main ones being that it reaches its limit at about 200 bases, partly due to side reactions than can occur during the synthesis procedure, and that it produces hazardous waste. For researchers, even 1,000 bases is considered a small gene, so to make longer sequences, the shorter ones are stitched together using a process that is failure-prone and can’t make certain sequences.

    Buying your genes online

    A DNA sequence is made up of a combination of four chemical bases, represented by the letters A, C, T, and G. Researchers regularly work with genes of several thousand bases in length. To obtain them, they either need to isolate the genes from an existing organism, or they can order the genes from a company.

    “You literally paste the sequence into a website, then wait two weeks,” Arlow said. “Let’s say you buy 10 genes. Maybe nine of them will be delivered to you on time. In addition, if you want to test a thousand genes, at $300 per gene, the costs add up very quickly.”

    Palluk and Arlow were motivated to work on this problem because, as students, they were spending many long, tedious hours making DNA sequences for their experiments when they would much rather have been doing the actual experiment.

    “DNA is a huge biomolecule,” Palluk said. “Nature makes biomolecules using enzymes, and those enzymes are amazingly good at handling DNA and copying DNA. Typically our organic chemistry processes are not anywhere close to the precision that natural enzymes offer.”

    Faster, Cheaper, Better Way to Make DNA

    Thinking outside the box

    The idea of using an enzyme to make DNA is not new – scientists have been trying for decades to find a way to do it, without success. The enzyme of choice is called TdT (terminal deoxynucleotidyl transferase), which is found in the immune system of vertebrates and is one of the few enzymes in nature that writes new DNA from scratch rather than copying DNA. What’s more, it’s fast, able to add 200 bases per minute.

    In order to harness TdT to synthesize a desired sequence, the key requirement is to make it add just one nucleotide, or DNA building block, and then stop before it keeps adding the same nucleotide repeatedly. All of the previous proposals envisioned using nucleotides modified with special blocking groups to prevent multiple additions. However, the problem is that the catalytic site of the enzyme is not large enough to accept the nucleotide with a blocking group attached. “People have basically tried to ‘dig a hole’ in the enzyme by mutating it to make room for this blocking group,” Arlow said. “It’s tricky because you need to make space for it but also not screw up the activity of the enzyme.”

    Palluk and Arlow came up with a different approach. “Instead of trying to dig a hole in the enzyme, what we do is tether one nucleotide to each TdT enzyme via a cleavable linker,” Arlow said. “That way, after extending a DNA molecule using its tethered nucleotide, the enzyme has no other nucleotides available to add, so it stops. A key advantage of this approach is that the backbone of the DNA – the part that actually does the chemical reaction – is just like natural DNA, so we can try to get the full speed out of the enzyme.”

    Once the nucleotide is added to the DNA molecule, the enzyme is cleaved off. Then the cycle can begin again with the next nucleotide tethered to another TdT enzyme.

    Keasling finds the approach clever and counterintuitive. “Rather than reusing an enzyme as a catalyst, they said, ‘Hey, we can make enzymes really inexpensively. Let’s just throw it away.’ So the enzyme becomes a reagent rather than a catalyst,” he said. “That kind of thinking then allowed them to do something very different from what’s been proposed in the literature and – I think – accomplish something really important.”

    They demonstrated their method by manually making a DNA sequence of 10 bases. Not surprisingly, the two students were initially met with skepticism. “Even when we had first results, people would say, ‘It doesn’t make sense; it doesn’t seem right. That’s not how you use an enzyme,’” Palluk recalled.

    The two still have much work to do to optimize their method, but they are reasonably confident that they will be able to eventually make a gene with 1,000 bases in one go at many times the speed of the chemical method.

    Berkeley Lab has world-renowned capabilities in synthetic biology, technology development for biology, and engineering for biological process development. A number of technologies developed at JBEI and by the Lab’s Biosciences Area researchers have been spun into startups, including Lygos, Afingen, TeselaGen, and CinderBio.

    “After decades of optimization and fine-tuning, the conventional method now typically achieves a yield of about 99.5 percent per step. Our proof-of-concept synthesis had a yield of 98 percent per step, so it’s not quite on par yet, but it’s a promising starting point,” Palluk said. “We think that we’ll catch up soon and believe that we can push the system far beyond the current limitations of chemical synthesis.”

    “Our dream is to make a gene overnight,” Arlow said. “For companies trying to sustainably biomanufacture useful products, new pharmaceuticals, or tools for more environmentally friendly agriculture, and for JBEI and DOE, where we’re trying to produce fuels and chemicals from biomass, DNA synthesis is a key step. If you speed that up, it could drastically accelerate the whole process of discovery.”

    JBEI is a DOE Bioenergy Research Center funded by DOE’s Office of Science, and is dedicated to developing advanced biofuels. Other co-authors on the paper are: Tristan de Rond, Sebastian Barthel, Justine Kang, Rathin Bector, Hratch Baghdassarian, Alisa Truong, Peter Kim, Anup Singh, and Nathan Hillson.

    See the full article here .

    Please help promote STEM in your local schools.

    Stem Education Coalition

    A U.S. Department of Energy National Laboratory Operated by the University of California

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  • richardmitnick 12:38 pm on May 20, 2018 Permalink | Reply
    Tags: , , , Genetics,   

    From Astrobiology Magazine: “How primordial life on Earth might have replicated itself” 

    Astrobiology Magazine

    From Astrobiology Magazine

    May 20, 2018

    Liquid brine containing replicating RNA molecules is concentrated in the cracks between ice crystals, as seen with an electron microscope. Credit: Philipp Holliger, MRC LMB

    Scientists have created a new type of genetic replication system which demonstrates how the first life on Earth – in the form of RNA – could have replicated itself. The scientists from the Medical Research Council (MRC) Laboratory of Molecular Biology say the new RNA utilises a system of genetic replication unlike any known to naturally occur on Earth today.

    A popular theory for the earliest stages of life on Earth is that it was founded on strands of RNA, a chemical cousin of DNA. Like DNA, RNA strands can carry genetic information using a code of four molecular letters (bases), but RNA can be more than a simple ‘string’ of information. Some RNA strands can also fold up into three-dimensional shapes that can form enzymes, called ribozymes, and carry out chemical reactions.

    If a ribozyme could replicate folded RNA, it might be able to copy itself and support a simple living system.

    Previously, scientists had developed ribozymes that could replicate straight strands of RNA, but if the RNA was folded it blocked the ribozyme from copying it. Since ribozymes themselves are folded RNAs, their own replication is blocked.

    Now, in a paper published today in the journal eLife, the scientists have resolved this paradox by engineering the first ribozyme that is able to replicate folded RNAs, including itself.

    Normally when copying RNA, an enzyme would add single bases (C, G, A or U) one at a time, but the new ribozyme uses three bases joined together, as a ‘triplet’ (e.g. GAU). These triplet building blocks enable the ribozyme to copy folded RNA, because the triplets bind to the RNA much more strongly and cause it to unravel – so the new ribozyme can copy its own folded RNA strands.

    The scientists say that the ‘primordial soup’ could have contained a mixture of bases in many lengths – one, two, three, four or more bases joined together – but they found that using strings of bases longer than a triplet made copying the RNA less accurate.

    Dr Philipp Holliger, from the MRC Laboratory of Molecular Biology and senior author on the paper, said: “We found a solution to the RNA replication paradox by re-thinking how to approach the problem – we stopped trying to mimic existing biology and designed a completely new synthetic strategy. It is exciting that our RNA can now synthesise itself.

    “These triplets of bases seem to represent a sweet spot, where we get a nice opening up of the folded RNA structures, but accuracy is still high. Notably, although triplets are not used in present-day biology for replication, protein synthesis by the ribosome – an ancient RNA machine thought to be a relic of early RNA-based life – proceeds using a triplet code.

    “However, this is only a first step because our ribozyme still needs a lot of help from us to do replication. We provided a pure system, so the next step is to integrate this into the more complex substrate mixtures mimicking the primordial soup – this likely was a diverse chemical environment also containing a range of simple peptides and lipids that could have interacted with the RNA.”

    The experiments were conducted in ice at -7°C, because the researchers had previously discovered that freezing concentrates the RNA molecules in a liquid brine in tiny gaps between the ice crystals. This also is beneficial for the RNA enzymes, which are more stable and function better at cold temperatures.

    Dr Holliger added: “This is completely new synthetic biology and there are many aspects of the system that we have not yet explored. We hope in future, it will also have some biotechnology applications, such as adding chemical modifications at specific positions to RNA polymers to study RNA epigenetics or augment the function of RNA.”

    Dr Nathan Richardson, Head of Molecular and Cellular Medicine at the MRC, said: “This is a really exciting example of blue skies research that has revealed important insights into how the very beginnings of life may have emerged from the ‘primordial soup’ some 3.7 billion years ago. Not only is this fascinating science, but understanding the minimal requirements for RNA replication and how these systems can be manipulated could offer exciting new strategies for treating human disease.”

    See the full article here .

    Please help promote STEM in your local schools.


    Stem Education Coalition

  • richardmitnick 11:21 am on April 25, 2018 Permalink | Reply
    Tags: , FOXG1, Genetics, , Soo-Kyung a specialist in genetics, Yuna Lee   

    From The New York Times: “Infinitesimal Odds: A Scientist Finds Her Child’s Rare Illness Stems From the Gene She Studies” 

    New York Times

    The New York Times

    April 23, 2018
    Pam Belluck

    By the time her mother received the doctor’s email, Yuna Lee was already 2 years old, a child with a frightening medical mystery. Plagued with body-rattling seizures and inconsolable crying, she could not speak, walk or stand.

    “Why is she suffering so much?” her mother, Soo-Kyung Lee, anguished. Brain scans, genetic tests and neurological exams yielded no answers. But when an email popped up suggesting that Yuna might have a mutation on a gene called FOXG1, Soo-Kyung froze.

    “I knew,” she said, “what that gene was.”

    Almost no one else in the world would have had any idea. But Soo-Kyung is a specialist in the genetics of the brain—“a star,” said Robert Riddle, a program director in neurogenetics at the National Institute of Neurological Disorders and Stroke. For years, Soo-Kyung, a developmental biologist at Oregon Health and Science University, had worked with the FOX family of genes.

    “I knew how critical FOXG1 is for brain development,” she said.

    She also knew harmful FOXG1 mutations are exceedingly rare and usually not inherited — the gene mutates spontaneously during pregnancy. Only about 300 people worldwide are known to have FOXG1 syndrome, a condition designated a separate disorder relatively recently. The odds her own daughter would have it were infinitesimal.

    “It is an astounding story,” Dr. Riddle said. “A basic researcher working on something that might help humanity, and it turns out it directly affects her child.”

    Suddenly, Soo-Kyung, 42, and her husband Jae Lee, 57, another genetics specialist at O.H.S.U., had to transform from dispassionate scientists into parents of a patient, desperate for answers.

    Soo-Kyung and Yuna on a FaceTime call with Soo-Kyung’s parents in Korea.CreditRuth Fremson/The New York Times.

    Yuna during free playtime in the schoolyard at Bridlemile Elementary School in Portland, Ore. Yuna cannot walk, but she spends time daily in a gait trainer to help her learn to propel herself with her feet.CreditRuth Fremson/The New York Times.

    They were plunged into a fast-moving ocean of newly identified gene mutations, newly named diagnoses, and answers that raise new questions.The newfound capacity to sequence genomes is spurring a genetic gold rush, linking mystifying diseases to specific mutations — often random mutations not passed down from parents.

    New research shows that each year, about 400,000 babies born worldwide have neurological disorders caused by random mutations, said Matthew Hurles, head of human genetics at Wellcome Trust Sanger Institute. As sequencing becomes cheaper, more children will receive specific diagnoses like FOXG1 syndrome, doctors say.

    This burst of discovery might eventually help doctors treat or prevent some brain damage. “We used to lump them all together under autism or another category,” said Dr. Joseph Gleeson, a neurogeneticist at University of California San Diego. “It’s really changing the way doctors are thinking about disease.”

    Balancing the missions of science and motherhood, Soo-Kyung has begun doing what she is uniquely positioned to do: aiming her research squarely at her daughter’s disorder. With Jae’s help, she is studying how the FOXG1 gene works and why mutations like Yuna’s are so devastating.

    “Our ultimate goal is to find a better treatment for FOXG1 syndrome patients,” she said. Her day-to-day goal is helping Yuna make slivers of developmental progress.

    Yuna is now a sweet-natured 8-year-old still wearing a toddler’s onesie over a diaper. “Cognitively she’s about 18 months,” Jae, her father, said.

    A major achievement would be getting Yuna to indicate when her diaper is wet. Or to stand when they prop her against a kitchen corner and remove their hands for a split second. “If Yuna doesn’t fall down right away,” Soo-Kyung said, “we consider that a success.”

    “My daughter’s brain is so damaged,” Soo-Kyung said, eyes brimming with tears. “Can we rescue any of her skills?”

    Soo-Kyung, left, and Jae, right, work next door to each other; together they are researching FOXG1 syndrome, the rare disorder Yuna has.CreditRuth Fremson/The New York Times

    When their daughter was born in Houston in January 2010, southeast Texas experienced a rare snowfall. It inspired the Lees, then professors at Baylor College of Medicine, to name her “Yuna,” meaning “snow girl” in a Korean dialect, with the middle name “Heidi” for its allusion to snowy peaks.

    “She was perfectly normal,” Jae said. “We were joking, ‘What will come later?’ Yuna’s mom is a very smart person, so we thought, ‘Well, she will make the world better.’”

    But soon, things seemed off. Yuna often failed to respond to sounds. She struggled to swallow milk from breast or bottle. What she did swallow she vomited. “She looked like someone with malnutrition,” Soo-Kyung said.

    A doctor said her head circumference was not growing enough. Then Yuna began having seizures , often sending the Lees to the emergency room. She cried so persistently that Soo-Kyung had to assure neighbors Yuna was not being abused.

    “What did I do wrong?” Soo-Kyung grilled herself. Had she eaten something while pregnant that infected Yuna? “I was traveling a lot during the pregnancy to attend seminars — was I too stressed?”

    Yuna and her mother in a family photo. Born in Texas during a rare snowfall, her name, Yuna, means “snow girl” in a Korean dialect. No image credit.

    Shortly after Yuna’s second birthday, Soo-Kyung traveled to Washington, D.C. to serve on a National Institutes of Health panel reviewing grant proposals from brain development researchers. At dinner, she found herself next to Dr. David Rowitch, a respected neonatologist and neuroscientist she knew only by reputation.

    “She started to tell me what’s going on with her daughter,” recalled Dr. Rowitch, professor and head of pediatrics at the University of Cambridge who was then at the University of California San Francisco. He was stumped but offered to send Yuna’s brain scans to “the world’s expert” in neuroradiology: Dr. Jim Barkovich at U.C.S.F.

    Dr. Barkovich said Yuna’s scans revealed “a very unusual pattern,” one he had not seen in decades of evaluating brain images sent to him from around the world. Yuna’s cerebral cortex had abnormal white matter, meaning “there were probably cells dying,” he said, and the corpus callosum, the corridor across which cells in the left and right hemispheres communicate, was “way too thin.”

    Searching scientific literature, he said, “I found a gene that seemed to be expressed in that area and found that when it was mutated it caused a very similar pattern.” That gene was FOXG1.

    Left, Soo-Kyung watching a postdoctoral student with mouse brains in her lab at OHSU. Right, examining mouse brain cells. She has begun aiming her research at understanding Yuna’s brain disorder.CreditRuth Fremson/The New York Times.

    Yuna exploring her mother’s closet after her bath. Her mother, Soo-Kyung, began sleeping on the mattress after she collapsed from the stress of caring for Yuna; sleeping in the closet helps Soo-Kyung rest without noise or distraction.CreditRuth Fremson/The New York Times.

    FOXG1 is so crucial that its original name was “Brain Factor 1,” said Dr. William Dobyns, a professor of pediatrics and neurology at University of Washington, who published a 2011 study recommending a separate diagnosis: FOXG1 syndrome. “It’s one of the most important genes in brain development.”

    FOXG1 provides blueprints for a protein that helps other genes switch on or off. It helps with three vital fetal brain stages: delineating the top and bottom regions, adjusting the number of nerve cells produced and “setting up the organization of the entire cortex,” Dr. Dobyns said.

    So, when Dr. Barkovich’s email said he “would not be surprised if this is a FOXG1 mutation,” Soo-Kyung’s heart shuddered. “That’s unthinkable,” she despaired.

    Yuna’s neurologist declined to authorize FOXG1 gene analysis, considering the possibility improbable — and irrelevant because it would not change Yuna’s treatment, Soo-Kyung said. So she decided to sequence the gene herself, preparing to seek university permission since her lab only worked with animals. Then, she became pregnant again. That provided justification for professional analysis of Yuna’s gene to determine if there was a heritable mutation the Lees could have also transmitted to their second child.

    When results showed a FOXG1 mutation, Soo-Kyung requested the raw data, hoping the lab had messed up. But scanning the data, Soo-Kyung spotted the problem instantly: Yuna was missing one nucleotide, Number 256 in the 86th amino acid of one copy of FOXG1, which has 489 amino acids.

    It was a random mutation, so she felt relief her second child was at little risk. But its location in the DNA sequence had given Yuna a smaller, incompletely functioning brain. A single mutation had disabled the entire gene.

    Music seems to calm Yuna, so her father Jae often plays guitar in the evenings. Yuna’s brother, Joon, 5, helps as he can.CreditRuth Fremson/The New York Times.

    Bridlemile Elementary School’s long hallway is both minefield and laboratory for Yuna. In a wheelchair or special walker, she is guided by a paraprofessional, Audrey Lungershausen, who tries to keep her from grabbing student artwork and coats, while encouraging her to identify balls and faces on a mural.

    Soo-Kyung must also navigate a daunting hallway. In June 2016, overcome by stress, she collapsed. Diagnosed with vestibular neuritis, an infection involving nerves linking the ear and brain, she was bedridden for weeks and struggled to stand. She still experiences vertigo and nausea walking the hall to her lab, “like I’m on a ship that’s constantly moving.”

    Her disability, glancingly parallel to her daughter’s, helps her understand that “the world that Yuna has to face with her limited ability to control her body — that must be really scary to her,” she said.

    While Yuna’s condition gives Soo-Kyung’s work personal importance, her own condition makes it harder. She cannot look at her computer more than 25 minutes straight, reads with a yellow filter often used by children with autism, and does visual exercises using paper images taped to her office wall..

    Like Yuna, Soo-Kyung needed physical, occupational and speech therapy. A psychiatrist prescribed an antidepressant. Instead of sleeping in Yuna’s room, Soo-Kyung began blocking out light and sound by sleeping on a mattress on the floor of the master bedroom closet. “They say I may not recover to a normal level.”

    Soo-Kyung’s peripheral vision being tested at an occupational therapy session. She suffered a collapse in 2016 from the stress of juggling her scientific career while caring for Yuna, and dealt with the after-effects of vertigo.CreditRuth Fremson/The New York Times.

    Long before Yuna was born, Soo-Kyung stumbled upon research she found fascinating, showing that mice missing both FOXG1 genes did not form brains. That would apply to humans, too. “There’s nobody who is missing two copies of the gene,” said Dr. Riddle of the National Institute of Neurological Disorders and Stroke. “They don’t survive.”

    Soo-Kyung told Jae she wanted to someday study how FOXG1 drives brain development. “Then Yuna arrived,” Jae said.

    Now, studying mouse brains, the Lees have identified genes that interact with FOXG1, helping explain why one crippled copy of FOXG1 damages the corpus callosum’s ability to transmit signals between hemispheres.

    “We now understand how this gene works and why,” Soo-Kyung said.

    Many mysteries remain. Individual FOXG1 mutations affect gene function differently, so one FOXG1 patient’s symptoms can vary from another’s. For example, Charles A. Nelson III, an expert in child development and neurodevelopmental disorders at Boston Children’s Hospital and Harvard Medical School, evaluated two 10-year-old patients with mutations in different locations and markedly distinct levels of impairment.

    Since patients like Yuna, with one dysfunctional and one functional FOXG1 gene, produce half the necessary FOXG1 protein, Soo-Kyung wonders if gene therapy could restore some protein or boost protein activity in the good gene.

    But because FOXG1 is crucial so early in development, Dr. Rowitch said, “I don’t think you can just go back when the baby’s born and build the brain back up.”

    Still, Dr. Dobyns said, “are there parts of FOXG1 syndrome that we might be able to fix once we understand it better? Sure, parts of it.”

    Yuna Lee with her speech therapist, Diana Deaibes at Shriners Hospital for Children in Portland, Ore. nearly a year ago. A computer program was used to teach her to communicate with her eyes by staring at something she likes onscreen. The hope is for her to eventually direct her gaze to show that she wants food or a toy.CreditRuth Fremson/The New York Times

    When Yuna was 6, Soo-Kyung, half-asleep in bed with her, noticed something extraordinary: Yuna was sitting up. “Am I dreaming?” Soo-Kyung wondered. For years, Yuna failed to learn this skill, usually mastered by six-month-old babies.

    Physical therapists had stopped Yuna’s sessions, saying “ ‘What’s the point of doing it when she’s not making any progress?’” Soo-Kyung recalled. She began painstakingly urging Yuna to push up using her elbow, never sure Yuna understood. Then, “suddenly Yuna was sitting up and I didn’t know how it happened.” Probably a fluke, Soo-Kyung thought—but soon Yuna began sitting up regularly.

    Experts say too little is understood about newly recognized neurological disorders to know children’s developmental limits. But the Lees believe the sitting-up success shows that if they persevere, Yuna can make incremental progress. Their next goal is for Yuna to communicate when she is hungry, uncomfortable or wants something.

    Speech therapists could not get Yuna to intentionally press a button activating a recorded voice saying things like “more.” “I don’t know if she understands what I am telling her,” said Diana Deaibes, a speech-language pathologist at Shriners Hospital for Children.

    But the Lees refused to let Shriners pause speech therapy, urging therapists to try teaching Yuna to stare at something she wants. “We insisted,” said Jae, optimistic even though they attempted visual communication before “and it was a complete mess — she wasn’t able to do it at all.”

    Ms. Deaibes tried pictures and then computer eye-gaze programs that track Yuna’s eye movements. After months of Ms. Deaibes darkening the room to minimize distractions, buckling Yuna to control her jerky movements, Yuna can now stare for about three seconds, causing barn doors to open in computerized farmyards and other onscreen responses. The Lees hope to train Yuna to choose toys or books with her eyes.

    At school, Yuna spends time in a regular second-grade classroom where social exposure helps her and enlightens other students, said Bridlemile’s principal, Brad Pearson. These days, she increasingly responds to her name with eye contact or sound and rarely puts school materials in her mouth anymore, said Jim Steranko, who teaches Yuna in Bridlemile’s learning resource center.

    Listening to a teacher read.CreditRuth Fremson/The New York Times.

    Therapists working with Yuna are uncertain whether she is cognitively able to understand that the label contains her name.CreditRuth Fremson/The New York Times.

    Ms. Lungershausen assists Yuna with everything, including feeding her and, with another aide’s help, changing her diapers. She recently made colorful shapes for Yuna to grab while the second-graders studied fractions. “We have our bad days,” Ms. Lungershausen said. But she said Yuna increasingly recognizes phrases like “Let’s find the library door,” recently “brought a Kleenex to her nose after being prompted” and “brought my hand to her mouth and ‘kissed’ it, deliberately, first time since I’ve known her.”

    At 41 pounds, Yuna weighs 10 pounds less than her little brother, Joon, 5, who has begun helping care for his older sister. One day, after Yuna’s state-funded caregiver, Anne Marie Nguyen, bathed her and propped her in a baby play center to dry her, Joon, announcing he had finished “going potty,” brushed Yuna’s hair. Seeing her rip the bathroom thermostat’s cover off, Joon pulled Yuna’s hands from the wall, saying, “Don’t touch that.”

    When Soo-Kyung returned home after lab work involving gene manipulation in mouse and chicken brains, she crouched on the playroom carpet, watching Yuna commando crawl and elbow herself to a sitting position. She lifted Yuna into the special walker, called a gait trainer and, waving toys, coaxed her to propel the contraption with her feet.

    Then came Yuna’s nightly FaceTime visit with her grandparents in South Korea, who sing and show pictures as Yuna intermittently eyes the screen. Later, Jae played guitar, while Soo-Kyung held Yuna, keeping her rangy arms from tearing into the instrument. Yuna smiled and bobbed.

    Soo-Kyung rarely used to mention her daughter to fellow scientists, but recently began thanking Yuna during presentations. “I was afraid every day that she might not be with me the next day,” Soo-Kyung said, voice breaking. “But she’s done amazing things that we wouldn’t dare to dream. So, how can anyone say she will never be able to do this, she will never be able to do that?”

    They carried Yuna upstairs to her giant crib, her body arching elastically. Carting her up and down is getting harder, so the Lees expect to move from the three-level, cliff-side house they bought to be closer, for Yuna’s sake, to the hospital and their labs. With breathtaking views of Mount St. Helens, it is an optimist’s house, where it is possible to see beyond the horizon.

    As Yuna, in the arms of her caregiver, Anne Marie Nguyen, grows, it gets harder to carry her up and down the house’s several flights of stairs.CreditRuth Fremson/The New York Times

    See the full article here .

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