Sir Isaac Newton probably wasn’t thinking about how animals urinate when he was developing his laws of gravity. But they are connected – by the urethra, to be specific.
A new Georgia Institute of Technology study investigated how quickly 32 animals urinate. It turns out that it’s all about the same. Even though an elephant’s bladder is 3,600 times larger than a cat’s (18 liters vs. 5 milliliters), both animals relieve themselves in about 20 seconds. In fact, all animals that weigh more than 3 kilograms (6.6 pounds) urinate in that same time span.
“It’s possible because larger animals have longer urethras,” said David Hu, the Georgia Tech assistant professor who led the study. “The weight of the fluid in the urethra is pushing the fluid out. And because the urethra is long, flow rate is increased.”
For example, an elephant’s urethra is one meter in length. The pressure of fluid in it is the same at the bottom of a swimming pool three feet deep. An elephant urinates four meters per second, or the same volume per second as five showerheads.
“If its urethra were shorter, the elephant would urinate for a longer time and be more susceptible to predators,” Hu explained.
The findings conflict with studies that indicate urinary flow is controlled on bladder pressure generated by muscular contraction. The study has just been published in the Proceedings of the National Academy of Sciences (PNAS).
Hu (George Woodruff School of Mechanical Engineering and School of Biology) and graduate student Patricia Yang noticed that gravity allows larger animals to empty their bladders in jets or sheets of urine. Gravity’s effect on small animals is minimal.
“They urinate in small drops because of high viscous and capillary forces. It’s like peeing in space,” said Yang, who is pursuing her doctoral degree in the School of Mechanical Engineering. “Mice and rats go in less than two seconds. Bats are done in a fraction of a second.”
The research team went to a zoo to watch 16 animals relieve themselves, then watched 28 YouTube videos. They saw cows, horses, dogs and more.
The more they watched, the more they realized their findings could help engineers.
“It turns out that you don’t need external pressure to get rid of fluids quickly,” said Hu. “Nature has designed a way to use gravity instead of wasting the animal’s energy.”
Hu envisions systems for water tanks, backpacks and fire hoses that can be built for more efficiency. As an example, he and his students have created a demonstration that empties a teacup, quart and gallon of water in the same duration using varying lengths of connected tubes. In a second experiment, the team fills three cups with the same amount of water, then watches them empty at differing rates. The longer the tube, the faster it empties.
“Nature has shown us that no matter how big the fire truck, water can still come out in the same time as a tiny truck,” Hu added.
The trick is gravity. Newton would be proud.
It’s 3:15 p.m. and the sun is setting at Anvers Island. Just off the Antarctic Peninsula, surrounded by 300-foot cliffs of ice, Jeannette Yen pauses outside Palmer Station to watch. The sun spills over the ice cliffs. The frozen landscape melts in a golden glow.
This is one of nature’s great laboratories. Yen and her team of scientists are conducting experiments here that are possible nowhere else. Outfitted in red parkas, they are not here to drill into frozen lakes or fly over thinning ice sheets. They spend what little daylight they have searching for tiny organisms in the frigid waters.
The scientists climb aboard the R/V Lawrence M Gould, a massive research vessel operated by the National Science Foundation (NSF). They cruise past giant icebergs and through rafts of loose ice to Palmer Deep, a location where the water is 2,000 feet (600 meters) deep. From the huge stern A-frame of the ship, they lower plankton nets into the zero-degree Celsius water and haul live animals aboard. In Antarctica, zero degrees Celsius is a pleasant day, but the recent bout of 80-knot wind gusts tells them the austral winter is on its way.
“The weather has been good,” Yen said. “We’ve gone out and have been collecting plankton all around.”
Yen, a professor of biology at the Georgia Institute of Technology in Atlanta, is on her second polar plunge. She’s an ecologist with an engineer’s eye. Her team of biologists and engineers haul each day’s catch back to the lab at Palmer Station, which provides no escape from the cold. There, the scientists study plankton swimming motion with video cameras in a room kept at zero degrees Celsius, to mimic the animals’ natural environment.
Plankton are the base of the food chain, but their environment is changing. Around the southern continent, the water temperature is stable at around zero degrees Celsius because of the Antarctic Circumpolar Current. Carbon dioxide, a potent greenhouse gas, easily dissolves in the cold water, acidifying the ocean. The acidifying oceans might be triggering a destructive chain of events underwater that could harm the food web around the world.
That’s why Yen and her team have come here, in search of a tiny organism that could be a canary in the coal mine of climate change.
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Written by Argonne National Laboratory
A study published in Scienceby researchers from the U.S. Department of Energy’s Argonne National Laboratory and co-authored by Georgia Tech may dramatically shift our understanding of the complex dance of microbes and minerals that takes place in aquifers deep underground. This dance affects groundwater quality, the fate of contaminants in the ground and the emerging science of carbon sequestration.
Deep underground, microbes don’t have much access to oxygen. So they have evolved ways to breathe other elements, including solid minerals like iron and sulfur.
The part that interests scientists is that when the microbes breathe solid iron and sulfur, they transform them into highly reactive dissolved ions that are then much more likely to interact with other minerals and dissolved materials in the aquifer. This process can slowly but steadily make dramatic changes to the makeup of the rock, soil and water.
“That means that how these microbes breathe affects what happens to pollutants — whether they travel or stay put — as well as groundwater quality,” said Ted Flynn, a scientist from Argonne and the Computation Institute at the University of Chicago and the lead author of the study.
About a fifth of the world’s population relies on groundwater from aquifers for their drinking water supply, and many more depend on the crops watered by aquifers.
For decades, scientists thought that when iron was present in these types of deep aquifers, microbes who can breathe it would out-compete those who cannot. There’s an accepted hierarchy of what microbes prefer to breathe, according to how much energy each reaction can theoretically yield. (Oxygen is considered the best overall, but it is rarely found deep below the surface.)
According to these calculations, of the elements that do show up in these aquifers, breathing iron theoretically provides the most energy to microbes. And iron is frequently among the most abundant minerals in many aquifers, while solid sulfur is almost always absent.
But something didn’t add up right. A lot of the microorganisms had equipment to breathe both iron and sulfur. This requires two completely different enzymatic mechanisms, and it’s evolutionarily expensive for microbes to keep the genes necessary to carry out both processes. Why would they bother, if sulfur was so rarely involved?
The team decided to redo the energy calculations assuming an alkaline environment — “Older and deeper aquifers tend to be more alkaline than pH-neutral surface waters,” said Argonne coauthor Ken Kemner — and found that in alkaline environments, it gets harder and harder to get energy out of iron.
“Breathing sulfur, on the other hand, becomes even more favorable in alkaline conditions,” Flynn said.
The team reinforced this hypothesis in the lab with bacteria under simulated aquifer conditions. The bacteria, Shewanella oneidensis, can normally breathe both iron and sulfur. When the pH got as high as 9, however, it could breathe sulfur, but not iron.
There was still the question of where microorganisms like Shewanella could find sulfur in their native habitat, where it appeared to be scarce.
The answer came from another group of microorganisms that breathe a different, soluble form of sulfur called sulfate, which is commonly found in groundwater alongside iron minerals. These microbes exhale sulfide, which reacts with iron minerals to form solid sulfur and reactive iron. The team believes this sulfur is used up almost immediately by Shewanella and its relatives.
“This explains why we don’t see much sulfur at any fixed point in time, but the amount of energy cycling through it could be huge,” Kemner said.
Indeed, when the team put iron-breathing bacteria in a highly alkaline lab environment without any sulfur, the bacteria did not produce any reduced iron.
“This hypothesis runs counter to the prevailing theory, in which microorganisms compete, survival-of-the-fittest style, and one type of organism comes out dominant,” Flynn said. Rather, the iron-breathing and the sulfate-breathing microbes depend on each other to survive.
Understanding this complex interplay is particularly important for sequestering carbon. The idea is that in order to keep harmful carbon dioxide out of the atmosphere, we would compress and inject it into deep underground aquifers. In theory, the carbon would react with iron and other compounds, locking it into solid minerals that wouldn’t seep to the surface.
Iron is one of the major players in this scenario, and it must be in its reactive state for carbon to interact with it to form a solid mineral. Microorganisms are essential in making all that reactive iron. Therefore, understanding that sulfur—and the microbe junkies who depend on it—plays a role in this process is a significant chunk of the puzzle that has been missing until now.
The study, “Sulfur-Mediated Electron Shuttling During Bacterial Iron Reduction,” appeared online in the May 1 edition of Science Express and was published in Science earlier this summer. Other authors on the study were Argonne scientists Bhoopesh Mishra (also of the Illinois Institute of Technology) and Edward O’Loughlin and Georgia Tech scientist Thomas DiChristina.
“The exciting findings reported in our study were made possible by combining the microbiology expertise of my laboratory in the School of Biology at Georgia Tech with the geochemical expertise of the Molecular Environmental Sciences group led by Ken Kemner at Argonne National Laboratory,” said Professor DiChristina, “The biogeochemical link between bacterial iron- and sulfur-breathing bacteria is important for survival of microbial communities in modern subsurface environments, and also provides clues to the evolution of ancient metabolic processes on an early Earth that lacked oxygen but contained large amounts of iron and sulfur.”
Funding for the research was provided by the U.S. Department of Energy’s Office of Science. The Advanced Photon Source (APS) is also supported by the DOE’s Office of Science. The team conducted X-ray analysis at the APS GeoSoilEnviroCARS beamline 13-ID-E, which is operated by the University of Chicago and jointly supported by the National Science Foundation and the DOE’s Office of Science. Additional support came from the National Institutes of Health and the National Science Foundation.
The Computation Institute (CI), a joint institute of the University of Chicago and Argonne National Laboratory, is an intellectual nexus for scientists and scholars pursuing multi-disciplinary research, and a resource center for developing and applying innovative computational approaches. Founded in 1999, it is home to over 200 faculty, fellows, and staff researching complex, system-level problems in such areas as biomedicine, energy and climate, astronomy and astrophysics, computational economics, social sciences and molecular engineering. CI is home to diverse projects including theCenter for Robust Decision Making on Climate and Energy Policy, the Center for Multiscale Theory and Simulation, the Urban Center for Computation and Data and Globus.
The Advanced Photon Source at Argonne National Laboratory is one of five national synchrotron radiation light sources supported by the U.S. Department of Energy’s Office of Science to carry out applied and basic research to understand, predict, and ultimately control matter and energy at the electronic, atomic, and molecular levels, provide the foundations for new energy technologies, and support DOE missions in energy, environment, and national security. To learn more about the Office of Science X-ray user facilities, visit the user facilities directory.
Argonne National Laboratory seeks solutions to pressing national problems in science and technology. The nation's first national laboratory, Argonne conducts leading-edge basic and applied scientific research in virtually every scientific discipline. Argonne researchers work closely with researchers from hundreds of companies, universities, and federal, state and municipal agencies to help them solve their specific problems, advance America's scientific leadership and prepare the nation for a better future. With employees from more than 60 nations, Argonne is managed by UChicago Argonne, LLC for the U.S. Department of Energy's Office of Science.
DOE’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, visit science.energy.gov.
Congratulations to Dr. Greg Gibson for being awarded a T32 training grant from the National Institute of General Medical Science. Titled, "Computational Biology and Predictive Health”, the grant will bridge Biology, Biomedical Engineering, Industrial Systems Engineering and Computer Science through the support of 4 graduate students each year over the five funding period. The Executive Committee for the grant includes Greg Gibson, Melissa Kemp, King Jordan and Nicoleta Serban.
New study, published in Hepatology, shows the regenerative capacity of liver cells
Patients suffering from chronic liver disease often develop liver fibrosis (the accumulation of scar tissue), which frequently results in cirrhosis, which means a loss of liver function, which often comes with a choice between a liver transplant and certain death.
It’s a perfect storm of terrible things as sustained fibrosis dampens the regenerative capacity of hepatocytes, thwarting their ability to make a therapeutic response, resulting in a grim prognosis and high mortality. At its essence, this is a communication problem, based on a study by a team of researchers in the lab of Chong Hyun Shin at the Georgia Institute of Technology.
Their findings explain how signaling pathways and cell-cell communications direct the cellular response to fibrogenic stimuli. But they also identify some novel potential therapeutic strategies for chronic liver disease. Results of the study (funded by the National Institutes of Health, the Emory/Georgia Tech Regenerative Engineering and Medicine Center, and Georgia Tech’s School of Biology) were published recently in the journal Hepatology.
“We aim to understand the molecular and cellular mechanisms that mediate the effects of sustained fibrosis on hepatocyte regeneration, using the zebrafish as a model,” explains Shin, assistant professor in the School of Biology, with a lab in the Parker H. Petit Institute for Bioengineering and Bioscience. Her fellow authors are Frank Anania (Emory), Mianbo Huang, Angela Chang, Minna Choi and David Zhou.
In their fibrotic zebrafish model, they studied the effects that different levels of signaling have on the regeneration of liver cells (hepatocytes). Specifically, they took note of the relationship between ‘Wnt’ and ‘Notch’ (signaling pathways). They discovered that lower level Notch signaling promotes cell regeneration (the proliferation and differentiation of hepatic progenitor cells, or HPCs, into hepatocytes), while high levels suppressed it. And they discovered that antagonistic interaction between Wnt and Notch modulates regenerative capacity: Wnt signals can suppress Notch signals, or, in other words, when Wnt is up, Notch is down, and hepatocyte regeneration can happen.
The data, says Shin, “suggest an essential interplay between Wnt and Notch signaling during hepatocyte regeneration in the fibrotic liver, providing legitimate therapeutic strategies for chronic liver failure in vivo.”
Inducing tissue regeneration via stem or progenitor cells, while delaying fibrosis, has been on the rise as antifibrogenic strategies of great potential, according to Shin, whose studies offer a clue of how to guide the differentiation of HPCs into hepatocytes in patients suffering from chronic liver failure. “Overall,” she explains, “employing the in vivo-based hepatic regeneration strategy may allow us to complement fundamental drawbacks in stem cell therapy, opening up new avenues of endogenous cellular regeneration therapy.”
This research is supported by grant number K01DK081351 from the National Institutes of Health (NIH), the Regenerative Engineering and Medicine Research Center Pilot Award (GTEC 2731336), and the School of Biology, Georgia Institute of Technology.
Read Hepatology journal abstract here
Pacific corals and fish can both smell a bad neighborhood, and use that ability to avoid settling in damaged reefs.
Damaged coral reefs emit chemical cues that repulse young coral and fish, discouraging them from settling in the degraded habitat, according to new research. The study shows for the first time that coral larvae can smell the difference between healthy and damaged reefs when they decide where to settle.
Coral reefs are declining around the world. Overfishing is one cause of coral collapse, depleting the herbivorous fish that remove the seaweed that sprouts in damaged reefs. Once seaweed takes hold of a reef, a tipping point can occur where coral growth is choked and new corals rarely settle.
The new study shows how chemical signals from seaweed repel young coral from settling in a seaweed-dominated area. Young fish were also not attracted to the smell of water from damaged reefs. The findings suggest that designating overfished coral reefs as marine protected areas may not be enough to help these reefs recover because chemical signals continue to drive away new fish and coral long after overfishing has stopped.
“If you’re setting up a marine protected area to seed recruitment into a degraded habitat, that recruitment may not happen if young fish and coral are not recognizing the degraded area as habitat,” said Danielle Dixson, an assistant professor in the School of Biology at the Georgia Institute of Technology in Atlanta, and the study's first author.
The study will be published August 22 in the journal Science. The research was sponsored by the National Science Foundation (NSF), the National Institutes of Health (NIH), and the Teasley Endowment to Georgia Tech.
The new study examined three marine areas in Fiji that had adjacent fished areas. The country has established no-fishing areas to protect its healthy habitats and also to allow damaged reefs to recover over time.
Juveniles of both corals and fishes were repelled by chemical cues from overfished, seaweed-dominated reefs but attracted to cues from coral-dominated areas where fishing is prohibited. Both coral and fish larvae preferred certain chemical cues from species of coral that are indicators of a healthy habitat, and they both avoided certain seaweeds that are indicators of a degraded habitat.
The study for the first time tested coral larvae in a method that has been used previously to test fish, and found that young coral have strong preferences for odors from healthy reefs.
"Not only are coral smelling good areas versus bad areas, but they’re nuanced about it," said Mark Hay, a professor in the School of Biology at Georgia Tech and the study's senior author. "They’re making careful decisions and can say, 'settle or don’t settle.'"
The study showed that young fish have an overwhelming preference for water from healthy reefs. The researchers put water from healthy and degraded habitats into a flume that allowed fish to choose to swim in one stream of water or the other. The researchers tested the preferences of 20 fish each from 15 different species and found that regardless of species, family or trophic group, each of the 15 species showed up to an eight times greater preference for water from healthy areas.
The researchers then tested coral larvae from three different species and found that they preferred water from the healthy habitat five-to-one over water from the degraded habitat.
Chemical cues from corals also swayed the fishes' preferences, the study found. The researchers soaked different corals in water and studied the behavior of fish in that water, which had picked up chemical cues from the corals. Cues of the common coral Acropora nasuta enhanced attraction to water from the degraded habitat by up to three times more for all 15 fishes tested. A similar preference was found among coral larvae.
Acropora corals easily bleach, are strongly affected by algal competition, and are prone to other stresses. The data demonstrate that chemical cues from these corals are attractive to fish and corals because they are found primarily in healthy habitats. Chemical cues from hardy corals, which can grow even in overfished habitats, were less attractive to juvenile fishes or corals.
The researchers also soaked seaweed in water and tested fish and coral preferences in that water. Cues from the common seaweed Sargassum polycystum, which can bloom and take over a coral reef, reduced the attractiveness of water to fish by up to 86 percent compared to water without the seaweed chemical cues. Chemical cues from the seaweed decreased coral larval attraction by 81 percent.
"Corals avoided that smell more than even algae that's chemically toxic to coral but doesn't bloom," Dixson said.
Future work will involve removing plots of seaweed from damaged reefs and studying how that impacts reef recovery.
A minimum amount of intervention at the right time and the right place could jump start the recovery of overfished reefs, Hay said. That could bring fish back to the area so they settle and eat the seaweed around the corals. The corals would then get bigger because the seaweed is not overgrown. Bigger corals would then be more attractive to more fish.
"What this means is we probably need to manage these reefs in ways that help remove the most negative seaweeds and then help promote the most positive corals," Hay said.
This research is supported by the National Science Foundation (NSF), under award number OCE-0929119, and the National Institutes of Health, under award number U01-TW007401. Any conclusions or opinions are those of the authors and do not necessarily represent the official views of the sponsoring agency.
CITATION: Dixson et al., "Chemically mediated behavior of recruiting corals and fishes: A tipping
point that may limit reef recovery." (August 2014, Science). http://www.sciencemag.org/content/345/6199/892
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Dr. Joel Kostka, a Professor jointly appointed in Biology and Earth & Atmospheric Sciences, was recently awarded $1.0 million in research grants by the U.S. Department of Energy (DOE) to study the microbially-mediated carbon cycle in boreal or northern peatlands. Peatlands sequester one-third of all soil carbon and currently act as major sinks of atmospheric CO2. The ability to predict or to simulate the fate of stored carbon in response to climatic disruption remains hampered by our limited understanding of the controls of C turnover and the composition and functioning of peatland microbial communities. Given their global extent and uncertain fate with climatic change, boreal or northern peatlands are considered a high priority for climate change research. The overall goal of this project is to investigate the rates, pathways, and controls of organic matter decomposition by microbes in response to warming and elevated carbon dioxide in peatlands. The project will be conducted at the Marcell Experimental Forest (MEF) in northern Minnesota where US Department of Energy’s (DOE) Oak Ridge National Laboratory (ORNL) and the USDA Forest Service are developing a climate manipulation field site known as Spruce and Peatland Response Under Climatic and Environmental Change (SPRUCE). In the Minnesota peatland, DOE is building 10 open top enclosures (12 m in diameter and 8 m in height). Inside these enclosures, the peat soil and air will be heated and carbon dioxide concentrations raised to simulate future climate change. Kostka’s project will examine changes to the microbial communities during this large scale climate change experiment. The project team includes collaborators at Florida State University and ORNL.
Dr. Kostka was interviewed last week by BBC radio on microbial hydrocarbon degradation (http://www.thenakedscientists.com/HTML/podcasts/specials/show/20140809/)
It also went out on the 5 Live show on Saturday morning - http://www.bbc.co.uk/programmes/b04cf3q8
GT Biology 2012 PhD graduate Douglas Rasher won the George Mercer Award from the Ecological Society of America this year. This prestigious award recognizes the best paper published in Ecology over the past 2 years by an ecologist younger than 40 years old. Rasher, now a postdoctoral research associate at the University of Maine, provides rich new insights for the management and conservation of coral reefs in his 2013 “Consumer diversity interacts with prey defenses to drive ecosystem function,” in Ecology. The study, which he conducted as a graduate student at the Georgia Institute of Technology, shows that interactions between algal defenses and herbivore tolerances create an essential role for consumer diversity in the functioning and resilience of coral reefs.
In an article in the September issue of BioScience, Samantha Joye and colleagues describe Gulf of Mexico microbial communities in the aftermath of the 2010 Macondo blowout. The authors describe revealing population-level responses of hydrocarbon-degrading microbes to the unprecedented deepwater oil plume.
The spill provided a unique opportunity to study the responses of indigenous microbial communities to a substantial injection of hydrocarbons. Surveys of genetic identifiers within cells known as ribosomal RNA and analyses relying on modern techniques including metagenomics, metatranscriptomics, and other methods revealed quickly changing population sizes and community structures. The presence of oil-degrading microbes, which was determined through the use of ribosomal RNA signatures, was found even after the dissipation of the initial plume, which provides evidence that seed populations persist and may be maintained by natural oil seepage or small accidental leaks.
Perhaps one of the most striking features of the microbial response to the blowout was the rapid formation of large flocs of marine “snow.” The flocs were initially observed in the upper water column and constituted the precursors to a massive pulse of oil-derived sediment that settled near the wellhead in the weeks following the accident. The rapid movement of oil to the seafloor in the form of microbe-induced marine snow represents a previously unrecognized outcome for marine hydrocarbons that may have far-reaching implications. The authors performed laboratory simulations of marine oil snow formation and identified several possible microbial mechanisms for the formation of the snow, including the creation of mucus webs through the action of bacterial oil degraders. As a result of their findings, Joye and her colleagues call for the inclusion of marine snow in the federal oil budget, which is intended to describe the fate of discharged oil.
The authors close with a call for additional research. Further study is needed both to increase the understanding of oil-degrading microbes and to quantify the rates at which they may degrade spilled oil.
The ability to accurately repair DNA damaged by spontaneous errors, oxidation or mutagens is crucial to the survival of cells. This repair is normally accomplished by using an identical or homologous intact sequence of DNA, but scientists have now shown that RNA produced within cells of a common budding yeast can serve as a template for repairing the most devastating DNA damage – a break in both strands of a DNA helix.
Earlier research had shown that synthetic RNA oligonucleotides introduced into cells could help repair DNA breaks, but the new study is believed to be the first to show that a cell’s own RNA could be used for DNA recombination and repair. The finding provides a better understanding of how cells maintain genomic stability, and if the phenomenon extends to human cells, could potentially lead to new therapeutic or prevention strategies for genetic-based disease.
The research was supported by the National Science Foundation, the National Institutes of Health and the Georgia Research Alliance. The results were reported September 3, 2014, in the journal Nature.
“We have found that genetic information can flow from RNA to DNA in a homology-driven manner, from cellular RNA to a homologous DNA sequence,” said Francesca Storici, an associate professor in the School of Biology at the Georgia Institute of Technology and senior author of the paper. “This process is moving the genetic information in the opposite direction from which it normally flows. We have shown that when an endogenous RNA molecule can anneal to broken homologous DNA without being removed, the RNA can repair the damaged DNA. This finding reveals the existence of a novel mechanism of genetic recombination.”
Most newly-transcribed RNA is quickly exported from the nucleus to the cytoplasm of cells to perform its many essential roles in gene coding and expression, and in regulation of cell operations. Generally, RNA is kept away from – or removed from – nuclear DNA. In fact, it is known that annealing of RNA with complementary chromosomal DNA is dangerous for cells because it may impair transcription elongation and DNA replication, promoting genome instability.
This new study reveals that under conditions of genotoxic stress, such as a break in DNA, the role of RNA paired with complementary DNA may be different, and beneficial, for a cell. “We discovered a mechanism in which transcript RNA anneals with complementary broken DNA and serves as a template for recombination and DNA repair, and thus has a role in both modifying and stabilizing the genome,” Storici explained.
DNA damage can arise from a variety of causes both inside and outside the cell. Because the DNA consists of two complementary strands, one strand can normally be used to repair damage to the other. However, if the cell sustains breakage in both strands – known as a double-strand break – the repair options are more limited. Simply rejoining the broken ends carries a high risk of unwanted mutations or chromosome rearrangement, which can cause undesirable effects including cancer. Without successful repair, however, the cell may die or be unable to carry out important functions.
Beginning in 2007, Storici’s research team showed that synthetic RNA introduced into cells – including human cells – could repair DNA damage, but the process was inefficient and there were questions about whether the process could occur naturally.
To find out whether cells could use endogenous RNA transcripts to repair DNA damage, she and graduate students Havva Keskin and Ying Shen – who are first and second authors on the paper – devised experiments using the yeast Saccharomyces cerevisiae, which is widely used in the lab for genetics and genome engineering. The researchers developed a strategy for distinguishing repair by endogenous RNA from repair by the normal DNA-based mechanisms in the budding yeast cells, including using mutants that lacked the ability to convert the RNA into a DNA copy. They then induced a DNA double-strand break in the yeast genome and observed whether the organism could survive and grow by repairing the damage using only transcript RNA within the cells.
The DNA region that generates the transcript was constructed to contain a marker gene interrupted by an intron, which is a sequence that is removed only from the RNA during the process of transcription, explained Keskin. Following intron removal, the transcript RNA sequence has no intron, while the DNA region that generates the transcript retains the intron; thus they are distinguishable. Only the repair templated by the transcript devoid of the intron can restore the function of a homologous marker gene in which the DNA double-strand break is induced, she added.
The researchers measured success by counting the number of yeast colonies growing on a Petri dish, indicating that the repair had been made by endogenous RNA. Testing was done on two types of breaks, one in the DNA from which the RNA transcript had been made, and the other in a homologous sequence from a different location in the DNA.
The research team, which also included scientists from Drexel University, found that proximity of the RNA to the broken DNA increased the efficiency of the repair and that the repair occurred via a homologous recombination process. Storici believes that the repair mechanism may operate in cells beyond yeast, and that many types of RNA can be used.
“We are showing that the flow of genetic information from RNA to DNA is not restricted to retro-elements and telomeres, but occurs with a generic cellular transcript, making it more of a general phenomenon than had been anticipated,” she explained. “Potentially, any RNA in the cell could have this function.”
For the future, Storici hopes to learn more about the mechanism, including what regulates it. She also wants to learn whether it takes place in human cells. If so, that could have implications for treating or preventing diseases that are caused by genetic damage.
“Cells synthesize lots of RNA transcripts during their life spans; therefore, RNA may have an unanticipated impact on genomic stability and plasticity,” said Storici, who is also a Georgia Research Alliance Distinguished Cancer Scientist. “We need to understand in which situations cells would activate RNA-DNA recombination. Better understanding this molecular process could also help us manipulate mechanisms for therapy, allowing us to treat a disease or prevent it altogether.”
In addition to Storici, the paper’s authors include Alexander Mazin, a professor in the Department of Biochemistry and Molecular Biology at Drexel University; postdoctoral fellow Fei Huang and graduate student Mikir Patel, also from Drexel; Havva Keskin, a Georgia Tech graduate student; Ying Shen, a Ph.D. graduate from Georgia Tech who is now a postdoctoral fellow at Boston University School of Medicine; and graduate student Taehwan Yang and undergraduate student Katie Ashley from School of Biology at Georgia Tech.
This research is supported by the National Science Foundation under award number MCB-1021763, by the National Institutes of Health under award numbers CA100839 and P30CA056036, and by the Georgia Research Alliance under award number R9028. Any conclusions or opinions are those of the authors and do not necessarily represent the official views of the sponsoring agencies.
CITATION: Havva Keskin, et al., “Transcript-RNA-templated DNA recombination and repair,” Nature 2014. http://dx.doi.org/10.1038/nature13682
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