A corny turn for biofuels from switchgrass

 

Introducing a maize gene into switchgrass substantially boosted the potential of the switchgrass biomass as an advanced biofuel feedstock. (Photo courtesy of USDA/ARS)                                                                                                              Many experts believe that advanced biofuels made from cellulosic biomass are the most promising alternative to petroleum-based liquid fuels for a renewable, clean, green, domestic source of transportation energy.

Nature, however, does not make it easy. Unlike the starch sugars in grains, the complex polysaccharides in the cellulose of plant cell walls are locked within a tough woody material called lignin. For advanced biofuels to be economically competitive, scientists must find inexpensive ways to release these polysaccharides from their bindings and reduce them to fermentable sugars that can be synthesized into fuels.

An important step towards achieving this goal has been taken by researchers with the U.S. Department of Energy (DOE)’s Joint BioEnergy Institute (JBEI), a DOE Bioenergy Research Center led by the Lawrence Berkeley National Laboratory (Berkeley Lab).

A team of JBEI researchers, working with researchers at the U.S. Department of Agriculture’s Agricultural Research Service (ARS), has demonstrated that introducing a maize (corn) gene into switchgrass, a highly touted potential feedstock for advanced biofuels, more than doubles (250 percent) the amount of starch in the plant’s cell walls and makes it much easier to extract polysaccharides and convert them into fermentable sugars. The gene, a variant of the maize gene known as Corngrass1 (Cg1), holds the switchgrass in the juvenile phase of development, preventing it from advancing to the adult phase.

“We show that Cg1 switchgrass biomass is easier for enzymes to break down and also releases more glucose during saccharification,” says Blake Simmons, a chemical engineer who heads JBEI’s Deconstruction Division and was one of the principal investigators for this research. “Cg1 switchgrass contains decreased amounts of lignin and increased levels of glucose and other sugars compared with wild switchgrass, which enhances the plant’s potential as a feedstock for advanced biofuels.”

The results of this research are described in a paper published in the Proceedings of the National Academy of Sciences (PNAS) titled “Overexpression of the maize Corngrass1 microRNA prevents flowering, improves digestibility, and increases starch content of switchgrass.”

Lignocellulosic biomass is the most abundant organic material on earth. Studies have consistently shown that biofuels derived from lignocellulosic biomass could be produced in the United States in a sustainable fashion and could replace today’s gasoline, diesel and jet fuels on a gallon-for-gallon basis. Unlike ethanol made from grains, such fuels could be used in today’s engines and infrastructures and would be carbon-neutral, meaning the use of these fuels would not exacerbate global climate change. Among potential crop feedstocks for advanced biofuels, switchgrass offers a number of advantages. As a perennial grass that is both salt- and drought-tolerant,  switchgrass can flourish on marginal cropland, does not compete with food crops, and requires little fertilization. A key to its use in biofuels is making it more digestible to fermentation microbes.

Overxpression of the Cg1 gene in switchgrass (left) compared to Wild-type of switchgrass of the same age and grown under the same conditions. (Photo courtesy of USDA/ARS)

“The original Cg1 was isolated in maize about 80 years ago. We cloned the gene in 2007 and engineered it into other plants, including switchgrass, so that these plants would replicate what was found in maize,” says George Chuck, lead author of the PNAS paper and a plant molecular geneticist who holds joint appointments at the Plant Gene Expression Center with ARS and the University of California (UC) Berkeley. “The natural function of Cg1 is to hold pants in the juvenile phase of development for a short time to induce more branching. Our Cg1 variant is special because it is always turned on, which means the plants always think they are juveniles.”

Chuck and his colleague Sarah Hake, another co-author of the PNAS paper and director of the Plant Gene Expression Center, proposed that since juvenile biomass is less lignified, it should be easier to break down into fermentable sugars. Also, since juvenile plants don’t make seed, more starch should be available for making biofuels. To test this hypothesis, they collaborated with Simmons and his colleagues at JBEI to determine the impact of introducing the Cg1 gene into switchgrass.

In addition to reducing the lignin and boosting the amount of starch in the switchgrass, the introduction and overexpression of the maize Cg1 gene also prevented the switchgrass from flowering even after more than two years of growth, an unexpected but advantageous result.

“The lack of flowering limits the risk of the genetically modified switchgrass from spreading genes into the wild population,” says Chuck.

The results of this research offer a promising new approach for the improvement of dedicated bioenergy crops, but there are questions to be answered. For example, the Cg1 switchgrass biomass still required a pre-treatment to efficiently liberate fermentable sugars.

“The alteration of the switchgrass does allow us to use less energy in our pre-treatments to achieve high sugar yields as compared to the energy required to convert the wild type plants,” Simmons says. “The results of this research set the stage for an expanded suite of pretreatment and saccharification approaches at JBEI and elsewhere that will be used to generate hydrolysates for characterization and fuel production.”

Another question to be answered pertains to the mechanism by which Cg1 is able to keep switchgrass and other plants in the juvenile phase.

“We know that Cg1 is controlling an entire family of transcription factor genes,” Chuck says, “but we have no idea how these genes function in the context of plant aging. It will probably take a few years to figure this out.”

-Biotechnology Research News

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Co-authoring the PNAS paper with Chuck and Simmons were Christian Tobias, Lan Sun, Florian Kraemer, Chenlin Li, Dean Dibble, Rohit Arora, Jennifer Bragg, John Vogel, Seema Singh,  Markus Pauly and Sarah Hake.

This research was supported in part by DOE’s Office of Science and by the USDA-ARS.

A failing sense of smell can be reversed

“A new animal study suggests that with training, smell can improve.” 

In a new study scientists at NYU Langone Medical Center have shown that the sense of smell can be improved. The new findings, published online November 20, 2011, in Nature Neuroscience, suggest possible ways to reverse the loss of smell due to aging or disease.

Smell is unique among our senses, explains Donald A. Wilson, PhD, professor of child and adolescent psychiatry at NYU Langone Medical Center and senior research scientist at the Emotional Brain Institute at Nathan S. Kline Institute for Psychiatric Research, who led the study. The olfactory bulb, a structure beneath the frontal cortex that receives nerve impulses from the nose, also has direct connections to the amygdala, which controls emotions and physiology, and to higher-order regions like the prefrontal cortex, involved in cognition and planning.

“Unlike information from your eyes and ears that has gone through many connections to reach the frontal cortex, the olfactory system is just two connections away,” says Dr. Wilson. “The result is an immediate pathway from the environment through our nose to our memory.”

Although impairment in the sense of smell is associated with Alzheimer’s disease, Parkinson’s disease, schizophrenia, and even normal aging, exactly why smell weakens remains a mystery, but recent laboratory research led by Dr. Wilson reveals how it may occur. “We located where in the brain loss of smell may happen,” he says. “And we showed that training can improve the sense of smell, and also make it worse.”

Dr. Wilson and Julie Chapuis, PhD, a post-doctoral fellow, placed thirsty rats in boxes with a snout-sized hole in each of three walls and exposed them to brief blasts of odors through the middle hole. There were three smells in all: a mix of 10 chemicals from fruits, oils, cleaning agents, etc.; the same mixture with one chemical replaced by another; and the same mixture minus one of the chemicals. When the rodents identified one smell, they were rewarded with a sip of water by going to the hole in the left side wall, for another smell they received water by going to the right side wall.

Rats could readily distinguish between odors when a chemical had been replaced in one mixture, but when one component had simply been removed, they could not differentiate. The researchers then anesthetized the rats and inserted electrodes into their brains. Within the olfactory bulb, each smell produced a different pattern of electrical activity. But in the piriform (olfactory) cortex, a half-inch-sized area of the rat cerebral cortex, the odors that rats could tell apart produced distinct patterns of activity, while those the rats could not distinguish produced identical patterns.

Drs. Wilson and Chapuis then trained a new group of rats to discriminate between the odors the first animals couldn’t tell apart by rewarding them over and over with sips water for choosing the appropriate hole. “We made them connoisseurs,” says Dr. Wilson. In the rats’ piriform cortex, activity patterns elicited by these similar odors were now different as well.

They trained a third group of animals to ignore the difference between odors the first rats could readily distinguish by giving them water at the same hole after exposure to either odor. This effectively dulled their sense of smell: the rats couldn’t tell one smell from the other, even for a reward. Their loss of discrimination was reflected in the piriform cortex, which now produced similar electrical patterns in response to both odors.

“Our findings suggest that while olfactory impairment may reflect real damage to the sensory system, in some cases it may be a ‘use it or lose it’ phenomenon,” says Dr. Wilson. This opens the door for potential smell training therapies that could help restore smell function in some cases. “Odor training could help fix broken noses,” he says.

UGA scientists invent long-lasting, near infrared-emitting material

Materials that emit visible light after being exposed to sunlight are commonplace and can be found in everything from emergency signage to glow-in-the-dark stickers. But until now, scientists have had little success creating materials that emit light in the near-infrared range, a portion of the spectrum that only can be seen with the aid of night vision devices.

In a paper just published in the early online edition of the journal Nature Materials, however, University of Georgia scientists describe a new material that emits a long-lasting, near-infrared glow after a single minute of exposure to sunlight. Lead author Zhengwei Pan, associate professor of physics and engineering in the Franklin College of Arts and Sciences and the Faculty of Engineering, said the material has the potential to revolutionize medical diagnostics, give the military and law enforcement agencies a “secret” source of illumination and provide the foundation for highly efficient solar cells.

“When you bring the material anywhere outside of a building, one minute of exposure to light can create a 360-hour release of near-infrared light,” Pan said. “It can be activated by indoor fluorescent lighting as well, and it has many possible applications.”

The material can be fabricated into nanoparticles that bind to cancer cells, for example, and doctors could visualize the location of small metastases that otherwise might go undetected. For military and law enforcement use, the material can be fashioned into ceramic discs that serve as a source of illumination that only those wearing night vision goggles can see. Similarly, the material can be turned into a powder and mixed into a paint whose luminescence is only visible to a select few.

The starting point for Pan’s material is the trivalent chromium ion, a well-known emitter of near-infrared light. When exposed to light, its electrons at ground state quickly move to a higher energy state. As the electrons return to the ground state, energy is released as near-infrared light. The period of light emission is generally short, typically on the order of a few milliseconds.

The innovation in Pan’s material, which uses matrix of zinc and gallogermanate to host the trivalent chromium ions, is that its chemical structure creates a labyrinth of “traps” that capture excitation energy and store it for an extended period. As the stored energy is thermally released back to the chromium ions at room temperature, the compound persistently emits near-infrared light over period of up to two weeks.

In a process that Pan likens to perfecting a recipe, he and postdoctoral researcher Feng Liu and doctoral student Yi-Ying Lu spent three years developing the material. Initial versions emitted light for minutes, but through modifications to the chemical ingredients and the preparation—just the right amounts of sintering temperature and time—they were able to increase the afterglow from minutes to days and, ultimately, weeks.

“Even now, we don’t think we’ve found the best compound,” Pan said. “We will continuously tune the parameters so that we may find a much better one.”

The researchers spent an additional year testing the material—indoors and out, as well as on sunny days, cloudy days and rainy days—to prove its versatility. They placed it in freshwater, saltwater and even a corrosive bleach solution for three months and found no decrease in performance.

In addition to exploring biomedical applications, Pan’s team aims to use it to collect, store and convert solar energy. “This material has an extraordinary ability to capture and store energy,” Pan said, “so this means that it is a good candidate for making solar cells significantly more efficient.”

How the brain senses nutrient balance

There is no doubt that eating a balanced diet is essential for maintaining a healthy body weight as well as appropriate arousal and energy balance, but the details about how the nutrients we consume are detected and processed in the brain remain elusive. Now, a research study discovers intriguing new information about how dietary nutrients influence brain cells that are key regulators of energy balance in the body.

The study, published by Cell Press in the November 17 issue of the journal Neuron, suggests a cellular mechanism that may allow brain cells to translate different diets into different patterns of activity.

“The nutritional composition of meals, such as the protein:carbohydrate (sugar) ratio has long been recognized to affect levels of arousal and attention,” explains senior study author, Dr. Denis Burdakov, from the University of Cambridge. “However, while certain specialized neurons are known to sense individual nutrients, such as the sugar glucose, it remains unclear how typical dietary combinations of nutrients affect energy balance-regulating brain circuits.”

Dr. Burdakov and colleagues studied how physiological mixtures of nutrients influenced “orexin/hypocretin” neurons, which are known to be critical regulators of wakefulness and energy balance in the body. Previous research had demonstrated that orexin/hypocretin neurons are inhibited by glucose. Surprisingly, the current study revealed that physiologically relevant mixtures of amino acids, the nutrients derived from proteins (such as egg white), stimulated and activated the orexin/hypocretin neurons.

The researchers went on to show that when orexin/hypocretin neurons were simultaneously exposed to amino acids and sugars, the amino acids served to suppress the inhibitory influence of glucose.

Taken together, these results support a new and more complex nutrient-specific model for dietary regulation of orexin/hypocretin neurons. “We found that activity in the orexin/hypocretin system is regulated by macronutrient balance rather than simply by the caloric content of the diet, suggesting that the brain contains not only energy-sensing cells, but also cells that can measure dietary balance,” concludes Dr Burdakov.

“Our data support the idea that the orexin/hypocretin neurons are under a ‘push-pull’ control by sugars and proteins. Interestingly, although behavioral effects are beyond the scope of our study, this cellular model is consistent with reports that when compared with sugar-rich meals, protein-rich meals are more effective at promoting wakefulness and arousal.”

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New study explains how heart attack can lead to heart rupture

For people who initially survive a heart attack, a significant cause of death in the next few days is cardiac rupture — literally, bursting of the heart wall.

A new study by University of Iowa researchers pinpoints a single protein as the key player in the biochemical cascade that leads to cardiac rupture. The findings suggest that blocking the action of this protein, known as CaM kinase, may help prevent cardiac rupture and reduce the risk of death.

After a heart attack, the body produces a range of chemicals that trigger biological processes involved in healing and repair. Unfortunately, many of these chemical signals can become “too much of a good thing” and end up causing further damage often leading to heart failure and sudden death.

“Two of the medicines that are most effective for heart failure are beta-blockers, which block the action of adrenaline, and drugs that block the angiotensin receptor,” explains Mark E. Anderson, M.D., Ph.D., UI professor and head of internal medicine and senior study author. “The third tier of therapy is medication that blocks the action of aldosterone.”

Aldosterone levels increase in patients following a heart attack, and higher levels of the hormone are clearly associated with greater risk of death in the days immediately following a heart attack.

Increased aldosterone levels also are associated with a burst of oxidation in heart muscle, and in 2008, Anderson’s team showed that oxidation activates CaM kinase. Anderson’s research has also shown that CaM kinase is a lynchpin in the beta-blocker and angiotensin pathways.

“We wondered if aldosterone might somehow work through CaM kinase and, if it did, could some of the benefits of aldosterone blockers be attributed to effects on CaM kinase?” Anderson says.

Anderson’s team, including co-first authors Julie He (photo, below right), a student in the UI Medical Scientist Training Program; Mei-Ling Joiner, Ph.D.; Madhu Singh, Ph.D.; Elizabeth Luczak, Ph.D.; and Paari Swaminathan, M.D., devised a series of experiments in mice to investigate how elevated levels of aldosterone damage heart muscle after a heart attack and how Cam kinase is involved.

The experiments confirmed that aldosterone increases the amount of oxidized, and therefore, activated CaM kinase in heart muscle. Mice given excess aldosterone, mimicking levels seen in human patients, were twice as likely to die after a heart attack as mice that were not given extra aldosterone (70 percent vs. 35 percent), and the cause of death was heart rupture.

Importantly, any treatment that reduced the amount of oxidized CaM kinase or otherwise inhibited CaM kinase activity lowered the risk of cardiac rupture and death in the mice.

Interestingly, the researchers found that activated CaM kinase prompted heart muscle cells to produce an enzyme called MMP9 that is implicated in heart rupture.

“Although there are many sources of this enzyme, our study showed that heart muscle itself is actually making this protein too and is acting against its own self-interest in doing so,” Anderson says. “We don’t know why it happens, but inhibiting CaM kinase can prevent it.”

The MMP9 enzyme is involved in remodeling the “matrix” that surrounds heart cells. This matrix, which acts like mortar between cells, is constantly being broken down and rebuilt. In hearts that rupture after heart attack this remodeling process becomes excessive, weakening the matrix to the point that it ruptures.

Because matrix remodeling plays a role in other diseases, including cancer, Anderson notes that the CaM kinase findings may have clinical implications beyond heart disease.

Overall, the UI study suggests that blocking the biochemical processes triggered by aldosterone might help prevent cardiac rupture following a heart attack.

Anderson notes that a multi-center study currently underway in France is poised to determine if patients would benefit from getting aldosterone blockers right away rather than waiting several weeks.

“We think our study provides experimental evidence for why that should work,” he says.

“We have now identified CaM kinase as a critical component for the disease effects of the three core therapeutic pathways in heart, and we are closer to understanding fundamental elements of these signaling pathways,” Anderson says. “The findings enhance excitement that CaM kinase might be an important therapeutic target in heart disease, and developing Cam kinase inhibitors is a major goal for us so that we can move this from experimental findings to clinical testing.”

The research was funded in part by grants from the National Institutes of Health, the American Heart Association, UI Research Foundation and the Fondation Leducq Award to the Alliance for Calmodulin Kinase Signaling in Heart Disease.

The interdisciplinary research team included scientists from four departments in the UI Carver College of Medicine; the Iowa City Veterans Affairs Medical Center; Maastricht University in the Netherlands; University of Leuven in Belgium; and Ohio State University.

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Courtesy University of Iowa Health Care Media Relations, 200 Hawkins Drive, Room W319 GH, Iowa City, Iowa 52242-1009

MEDIA CONTACT: Jennifer Brown, 319-356-7124, jennifer-l-brown@uiowa.edu

Protection from severe malaria explained

Why do people with a hereditary mutation of the red blood pigment hemoglobin (as is the case with sickle-cell anemia prevalent in Africa) not contract severe malaria? Scientists in the group headed by Prof. Michael Lanzer of the Department of Infectious Diseases at Heidelberg University Hospital have now solved this mystery.

In red blood cells with normal hemoglobin, the malaria parasite Plasmodium falciparum establishes a trafficking system (yellow). The parasite’s proteins – encased in transport envelopes – (turquoise) use this system to directly access the cell surface of the red blood cell. Photo: courtesy of Science/AAAS.

A degradation product of the altered hemoglobin provides protection from severe malaria. Within the red blood cells infected by the malaria parasite, it blocks the establishment of a trafficking system used by the parasite’s special adhesive proteins – adhesins – to access the exterior of the blood cells. As a result, the infected blood cells do not adhere to the vessel walls, as is usually the case for this type of malaria. This means that no dangerous circulatory disorders or neurological complications occur. The research study has been published in the journal Science, appearing initially online.

In the 1940s, researchers already discovered that sickle-cell anemia with its characteristic blood mutation was particularly prevalent in certain population groups in Africa. They also survived malaria tropica, whose course is usually especially virulent. With malaria tropica, the malaria parasites (Plasmodia) enter the person after a bite of an infected Anopheles mosquito. The mosquito first multiplies in the person’s liver cells and then infects the red blood cells (erythrocytes). Once inside the erythrocytes, they divide again and ultimately destroy them. The nearly simultaneous bursting of all infected blood cells causes the characteristic symptoms, which include bouts of fever and anemia.

Adhesins on red blood cells cause circulatory disorders

In patients with malaria tropica, neurological complications such as paralysis, seizures, coma and severe brain damage also frequently occur. This is caused by an anomaly of the parasite Plasmodium falciparum. It forms special adhesins that reach the cell surface of the infected blood cell. Once there, it causes the erythrocytes to adhere to the vessel walls, preventing them from being recognized in the spleen as damaged and removed from circulation. The parasite’s protective mechanism results in smaller vessels closing, becoming inflamed and for example, prevents parts of the nervous system from being adequately supplied with oxygen.

In humans with mutated hemoglobin, these complications occur in a weakened form or not at all. “At the cell surface of infected erythrocytes with mutated hemoglobin, there are significantly fewer adhesins of the parasite than in normal red blood cells,” explained Prof. Lanzer, Director of the Dept. of Infectious Diseases, Parasitology. “For this reason, we had a closer look at the trafficking system within the host cell.” To this end, the team compared the blood cells with normal hemoglobin and two hemoglobin variants (hemoglobin S and hemoglobin C), which occur in around one-fifth of the African population in malaria-infected areas.

Trafficking system of the malaria parasite visualized for the first time

In red blood cells with mutated hemoglobin variants, the trafficking system disassembles into short pieces (yellow). Targeted transport of proteins to the surface does not occur. Photo: courtesy of Science/AAAS.

In so doing, the scientists used high-resolution microscopy techniques such as cryoelectron tomography to discover a new transport mechanism. The parasite uses a certain protein (actin) from the cytoskeleton (cellular skeleton) of the erythrocytes for its own trafficking network. “It forms a completely new structure that has nothing in common with the rest of the cytoskeleton,” explained Dr. Marek Cyrklaff, group leader at the Dept. of Infectious Diseases, Parasitology and first author of the article. “The vesicles with the adhesins reach the cell surface of the red blood cells directly via these actin filaments.”

In contrast to erythrocytes with the two hemoglobin variants, here only short pieces of actin filaments are found. Targeted transport to the surface is not possible. “The entire transport system of the malaria parasite is degenerated in these blood cells,” Cyrklaff added. Laboratory tests showed that the hemoglobins themselves were not responsible for this, but rather a degradation product, ferryl hemoglobin. This is an irreversibly damaged, chemically altered hemoglobin that is no longer able to bind oxygen.

The hemoglobins S and C are considerably more unstable than normal hemoglobin. As a result, blood cells with these variants contain ten times more ferryl hemoglobin than other erythrocytes. This high concentration destabilizes the binding of the actin structure and it disintegrates.

“With these results, we have now described a molecular mechanism for the first time that explains this hemoglobin variant’s protective effect against malaria,” Lanzer said.

This study is also featured on InformAfrica to inform the African people . 

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Literature:
Hemoglobins S and C interfere with Actin Remodeling in Plasmodium falciparum-Infected Erythrocytes: Marek Cyrklaff, Cecilia P. Sanchez, Nicole Kilian, Cyrille Bisseye, Jacques Simpore, Friedrich Frischknecht and Michael Lanzer. Science DOI: 10.1126/science.1213775

Worms reveal secrets of wound-healing response

The lowly and straightforward roundworm may be the ideal laboratory model to learn more about the complex processes involved in repairing wounds and could eventually allow scientists to improve the body’s response to healing skin wounds, a severe problem in diabetics and the elderly.

That’s the conclusion of biologists at the University of California, San Diego, who have discovered genes in the laboratory roundworm C. elegans that signal the presence of surface wounds and trigger another series of chemical reactions that allow the worms to quickly close cuts in their surfaces that would turn fatal if left unrepaired.

The scientists report in the December 6 issue of the journal Current Biology that these two findings and a third discovery they made in the worms, involving genes that inhibit wound healing, could allow scientists one day to design ways to improve the healing of cuts and sores by possibly blocking the action of these inhibitory genes or finding ways to enhance the chemical signalling and wound healing process. The journal is publishing an advance copy of their paper online this week.

“What we’ve shown in this paper is that a biochemical pathway is activated by wounding in the worms that involves calcium,” said Andrew Chisholm, a professor of biology at UC San Diego, who headed the research effort. “It’s been known for some time that one of the things that happens when you damage a cell is that calcium levels within the cell increase.”

But in a series of experiments with C. elegans, Chisholm and postdoctoral fellow Suhong Xu found out much more. They took time-lapse movies of areas around the transparent worms where they punctured the skin with a needle or laser. Then they monitored the calcium with a fluorescent protein to see how the calcium molecules spread from the point of injury. They also developed genetic screens to pinpoint the specific calcium pathway or “channel” signalling the wound's presence and stimulating the healing process.

“We think the channel is playing an important role in either sensing damage or responding to some other receptor that senses damage,” said Chisholm. “Is it sensing a change in the tension of the cell? Is it sensing some kind of change in electrical potential? We don’t know.”

While biomedical scientists have made great strides in understanding how the body responds to infections and chemically rebuilds the skin when the wound healing process is underway, very little is known about what happens within the cell or the body in the minutes or hours following injury. “That’s still a big, big question,” Chisholm said. “But we think we’ve made a start that will help us answer that question.”

He thinks the lowly roundworms may be the ideal animals to probe that question and others involving wound healing for various reasons: they are small, transparent, have a delicate surface susceptible to injury and a rapid wound response mechanism that keeps their surface wounds from being fatal.

“They have a hydrostatic skeleton in which the skin and muscles are under pressure to allow the animal to stay semi-rigid, so when you jab a worm with a needle it will, in effect, explode,” he said. “But remarkably, they don’t die when you do that because they have evolved ways to very rapidly close wounds to survive in the wild. In their natural environment, their predators try to exploit the worm’s vulnerable exoskeleton. A whole group of fungi with tiny spikes just sit around waiting for the worms to crawl over them so they can poke holes through their cuticle.”

“For us, they are easy to work with, because worms are small, easy to grow and they’re transparent, so when you put them on a slide, you can see the calcium clearly,” he said.

The transparent worms also allowed Chisholm and Xu to get their first glimpse of how the worms rapidly close their wounds. In a time lapse movie and in a series of photographs detailed in the paper, the researchers show how actin, a protein found in all cells that plays a role in muscle contraction, is recruited to and surrounds the wound, then closes the cut by tightening the actin like a purse string.

“We think that calcium is regulating this process,” said Chisholm, “because if you knock out calcium with a drug that chelates calcium, essentially locking it up, you don’t get the ring. If you have a genetic mutant worm with low levels of calcium, you don’t get the ring. But if you bathe this mutant in calcium, you can restore this ring.”

In addition, the researchers discovered in roundworms that a protein called DAPK-1 acts to inhibit the closure of wounds, raising the possibility that drugs that inhibit the action of this protein could improve the wound healing process in humans.

“Wound healing in humans is a much more complicated situation than this of course,” Chisholm said. “But the hope is that by learning more about the basic biology of wound responses, we can eventually learn how to heal wounds more quickly or, in the case of the elderly or those with diabetes, overcome their weakened responses to healing.”

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