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News Article | June 13, 2017
Site: www.eurekalert.org

Methods to improve water purification or build better batteries are problems that have challenged scientists for decades. Advances have inched forward, but rising demand moves the finish line further and further away. At the same time, the chemical reactions that make these improvements possible occur at scales invisible to the naked eye (the atomic scale) where liquids and solid surfaces meet, making the work even more difficult. Knowing how these chemical interactions occur at the solid-liquid interface is critical in problems of great interest to the Department of Energy (DOE), particularly as it relates to environmental and water quality issues that may be affected by large-scale energy production activities. Now, a new technique developed by a team including University of Delaware Prof. Neil Sturchio and colleagues at Argonne National Laboratory and the University of Illinois at Chicago has produced real-time observations documenting the chemical reactions that happen between liquids and solids. The technique provides data that can be used to improve predictions of how nutrients and contaminants will move in natural systems or to gauge the effectiveness of water purification methods where ion exchange is critical to sanitization. It also may help scientists tease out limiting factors to supercapacitors -- robust energy storage devices that are often used over common batteries to power consumer electronics, hybrid vehicles, even large industrial-scale power. Sturchio, a geochemist, has studied mineral/water interactions for 25 years with funding from DOE. He and his collaborators recently demonstrated a new way of studying the microscopic structure and processes that occur where minerals and water meet, using X-ray beams to trigger the reactions while capturing images of their effects on the mineral surface. Now using a method called Resonant Anomalous X-Ray Reflectivity (RAXR), the researchers are able to go one step further and distinguish the identity of the element being studied. "With our previous methods, we could see the atomic-scale electron density profile of the interfacial region -- a nanometer-thick zone including the mineral surface and the adjacent solution -- but couldn't uniquely identify the atomic layers," said Sturchio, professor and chair of the Department of Geological Sciences in UD's College of Earth, Ocean, and Environment. The technique requires a high-quality crystal so the researchers selected mica, a mineral similar in structure to the abundant clay minerals in soils that produces an atomically flat crystal useful in laboratory investigations of interfacial properties. The researchers reflected an intense X-ray beam off a mica sample in alternating contact with two different salt solutions containing rubidium and sodium chloride. By changing the angle of the beam, scientists were able to scan the interfacial profile at atomic scale. By changing the energy of the beam at a fixed angle, they could isolate the distribution of rubidium ions in the interfacial region. "In this case, we can tune in and ask specifically where is the rubidium? How is it attached to the mica crystal and how is it released to the solution?" he said. According to Sturchio, most chemical reactions in groundwater and in the atmosphere, as well as during industrial processes including water purification and some forms of energy storage, happen at surfaces such as electrodes or particles. As a chemical reaction occurs, ions are kicked off or pulled on and energy is exchanged. Understanding quantitatively how the ions are exchanged at this scale can be used to design chemical processes to improve water purification or understand how contaminants are transported in soil and groundwater. In this project, the researchers wanted to see what it would take to get the rubidium, an alkali metal, to release from the mica surface once it was attached. They accomplished this by quickly changing the solution flowing over the mica crystal from rubidium chloride to a more concentrated sodium chloride, then timed the reaction to determine how long it took for the rubidium ions to release (desorb) from the mica and for the sodium chloride ions to take their place (adsorb). Generally, adsorption reactions are thought to occur in milliseconds, but here it took 25 seconds for the rubidium to release from the surface (desorption) and the sodium ions to take its place (adsorption). The closer the rubidium was to the mineral/water interface, the more fixed its position became (because of electrostatic energy - the kind that makes a balloon stick to a wall after you rub it against a sweater) and the more energy was required to pry it away from the mica. Conversely, the more water molecules between the crystal's surface and the rubidium ion, the more wiggle room the rubidium had in its position and the less energy it took to break away. The experiments helped to quantify the minute amounts of energy transferred during alkali ion exchange at this interface, and the involvement of water molecules in the reaction mechanism. The reaction was slower than the researchers anticipated, and while further study is required, they agree the results provide evidence for understanding the timeframes necessary for desired reactions to occur. By contrast, when the solutions were switched back, the rubidium adsorbed onto the mica surface much more rapidly than it desorbed, by shedding its attached water molecules, demonstrating that hydration is important to the reaction. "To design an industrial process you need to know exactly what's happening at the surface," Sturchio said. "As far as we know, this is the first time anyone has documented such detailed information on how these ion exchange reactions are happening at a mineral surface in contact with water, and in this case, we have good evidence for how long it actually takes." The study was published Friday, June 9, in the journal Nature Communications. The work, titled "Real-time observations of cation exchange kinetics and dynamics at the muscovite-water interface," was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Chemical Sciences, Geosciences, and Biosciences Division under contracts DE-AC02-06CH11357. Sang Soo Lee, a clay mineralogist, and Paul Fenter, principal investigator on the project and a physicist and X-ray scattering expert, both with Argonne National Laboratory, designed the study. UD's Sturchio and Kathryn L. Nagy, a geochemist and clay mineral expert at University of Illinois at Chicago, were co-authors on the work.


News Article | June 8, 2017
Site: www.eurekalert.org

When the X-rays blast electrons out of one atom, stripping it from the inside out, it steals more from its neighbors -- a new insight that could help advance high-resolution imaging of whole viruses, bacteria and complex materials. With the most highly focused power of the world's most powerful X-ray laser, scientists from a number of institutions around the world- - including the U.S. Department of Energy's (DOE) Argonne National Laboratory -- have conducted a new experiment that takes apart molecules electron by electron. "The key to this experiment was being able to focus hard X-rays to a very tiny spot." The results of this experiment, carried out at DOE's SLAC National Accelerator Laboratory and published today in Nature, showed a surprising effect at the atomic scale. The researchers saw that a single laser pulse stripped all but a few electrons out of the molecule's biggest atom, leaving a void that started pulling in electrons from the rest of the molecule, like a black hole gobbling a spiraling disk of matter. Within 30 femtoseconds - millionths of a billionth of a second - the molecule lost more than 50 electrons, far more than scientists anticipated based on earlier experiments using less intense beams or isolated atoms. Then it blew up. "The key to this experiment was being able to focus hard X-rays to a very tiny spot," said Argonne scientist Linda Young, an author of the study. "By concentrating the X-rays on a single atom in a molecule, we can see and even predict -- on a very fast time scale -- the electron movement between different atoms in the molecule and track unusual behaviors." "This paper shows that we can understand and model the radiation damage in small molecules, so now we can predict what damage we will get in other systems," added Daniel Rolles of Kansas State University, another author of the study. The experiment gives scientists fundamental insights they need to better plan and interpret experiments using intense and energetic X-ray pulses, like those created by the free-electron X-ray laser at the Linac Coherent Light Source at SLAC. Experiments that require these ultrahigh intensities include attempts to image individual biological objects, such as viruses and bacteria, at high resolution. They are also used to study the behavior of matter under extreme conditions, and to better understand charge dynamics in complex molecules. The work represents a follow-on to an earlier experiment carried out by Young and other collaborators in 2010. The current experiment involves a much tighter focus of the X-ray energy, producing roughly 100 times higher intensity than previously achieved. The current study also involved a significant theoretical component. "Because this experiment involves such high intensities and so many electrons, the theory is quite elaborate - you must calculate many different trajectories on the fly for multiple electronic configurations and molecular geometries. Because everything is happening on the same ultrafast time scale, it's quite challenging," Young said. The experiment, led by Rolles and Artem Rudenko of Kansas State, took place at LCLS's Coherent X-ray Imaging (CXI) instrument. CXI delivers X-rays with the highest possible intensities achievable at LCLS and records data from samples in the instant before the laser pulse destroys them. How intense are those X-ray pulses? "They are about a hundred times more intense than what you would get if you focused all the sunlight that hits the Earth's surface onto a thumbnail," said LCLS staff scientist and co-author Sebastien Boutet. For this study, researchers used special mirrors to focus the X-ray beam into a spot just over 100 nanometers in diameter - about a hundredth the size of the one used in most CXI experiments, and a thousand times smaller than the width of a human hair. They looked at three types of samples: individual xenon atoms, which have 54 electrons each, and two types of molecules that each contain a single iodine atom, which has 53 electrons. Heavy atoms around this size are important in biochemical reactions, and researchers sometimes add them to biological samples to enhance contrast for imaging and crystallography applications. But until now, no one had investigated how the ultra-intense CXI beam affects molecules with atoms this heavy. The team tuned the energy of the CXI pulses so they would selectively strip the innermost electrons from the xenon or iodine atoms, creating "hollow atoms." Based on earlier studies with less energetic X-rays, they thought cascades of electrons from the outer parts of the atom would drop down to fill the vacancies, only to be kicked out themselves by subsequent X-rays. That would leave just a few of the most tightly bound electrons. And, in fact, that's what happened in both the freestanding xenon atoms and the iodine atoms in the molecules. But in the molecules, the process didn't stop there. The iodine atom, which had a strong positive charge after losing most of its electrons, continued to suck in electrons from neighboring carbon and hydrogen atoms, and those electrons were also ejected, one by one. Rather than losing 47 electrons, as would be the case for an isolated iodine atom, the iodine in the smaller molecule lost 54, including the ones it grabbed from its neighbors - a level of damage and disruption that's not only higher than would normally be expected, but significantly different in nature. "We think the effect was even more important in the larger molecule than in the smaller one, but we don't know how to quantify it yet," Rudenko said. "We estimate that more than 60 electrons were kicked out, but we don't actually know where it stopped because we could not detect all the fragments that flew off as the molecule fell apart to see how many electrons were missing. This is one of the open questions we need to study." For the data analyzed to date, the theoretical model provided excellent agreement with the observed behavior, providing confidence that more complex systems can now be studied, said LCLS director Mike Dunne. "This has important benefits for scientists wishing to achieve the highest-resolution images of biological molecules to inform the development of better pharmaceuticals, for example," he said. "These experiments will also guide the development of a next-generation instrument for the LCLS-II upgrade project, which will provide a major leap in capability due to the increase in repetition rate from 120 pulses per second to 1 million." The theory work for the study was led by Robin Santra of the Center for Free-Electron Laser Science at DESY and the University of Hamburg in Germany. Other research institutions contributing to the study were Tohoku University in Japan; Max Planck Institute for Nuclear Physics, Max Planck Institute for Medical Research, Hamburg Center for Ultrafast Imaging and the National Metrology Institute (PTB) in Germany; the University of Science and Technology in Beijing; Aarhus University in Denmark; Sorbonne University in France; the DOE's Argonne National Laboratory and Brookhaven National Laboratory; the University of Chicago; Kansas State University; and Northwestern University. Funding for the research came from the DOE Office of Science [Basic Energy Sciences, Chemical Sciences, Geosciences and Biosciences Division] and from the German Research Foundation (DFG). SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the U.S. Department of Energy Office of Science. To learn more, please visit http://www. . SLAC National Accelerator Laboratory is supported by the Office of Science of the U.S. Department of Energy. The 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, please visit science.energy.gov. 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. The U.S. Department of Energy'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 the Office of Science website.


News Article | May 31, 2017
Site: www.prweb.com

As part of the SyncD3 webinar series, Thermo Fisher Scientific will sponsor an event where attendees will learn from field scientists and researchers who are working in the ADME/Tox and drug discovery fields and offer an informative discussion on where these areas intersect, the impact on drug discovery and development, and the future of the industry during a live panel discussion with our presenters and you the audience. High content imaging and analysis offers a robust, high throughput analysis of large numbers of cells with the benefit of the spatial and temporal demarcation afforded by fluorescence microscopy. This webinar will provide an overview of high content imaging platforms, the fluorescent labels required to automate the segmentation of cells and their subcellular domains. Introduction to the newly developed fluorescent assays from Thermo Fisher Scientific will be provided, with an emphasis on those that provide an indication of cell viability, mechanisms of cell death, proliferation as well as the plethora of reagents that can be used to indicate pre-lethal toxicity. Newly developed phenotypic assays, in particular those used to profile CRISPR-Cas9 edited cells will also be discussed. The speaker for this webinar will be Dr. Nicholas Dolman, a senior staff scientist from the Biosciences Division at Thermo Fisher Scientific. Dr. Dolman received a doctorate of molecular and cellular physiology from the University of Liverpool and completed a post-doctoral fellowship at the NIH. He has been with Thermo Fisher Scientific for seven years and is currently a senior staff scientist in research and development. He has led the development of more than 50 products, covering a diverse range of technology platforms including fluorescent protein-based biosensors, Invitrogen™ Click-iT™ chemistry and environmentally sensitive dyes. LabRoots will host the webinar on June 13, 2017, beginning at 9:00 a.m. PDT, 12:00 p.m. EDT. To learn more about that SyncD3 webinar series, this specific event or to register for free, click here. About Thermo Fisher Scientific Thermo Fisher Scientific Inc. is the world leader in serving science, with revenues of $17 billion and more than 50,000 employees in 50 countries. Our mission is to enable our customers to make the world healthier, cleaner and safer. We help our customers accelerate life sciences research, solve complex analytical challenges, improve patient diagnostics and increase laboratory productivity. Through our premier brands – Thermo Scientific, Applied Biosystems, Invitrogen, Fisher Scientific and Unity Lab Services – we offer an unmatched combination of innovative technologies, purchasing convenience and comprehensive support. For more information, please visit http://www.thermofisher.com. About LabRoots LabRoots is the leading scientific social networking website, which provides daily scientific trending news and science-themed apparel, as well as produces educational virtual events and webinars, on the latest discoveries and advancements in science. Contributing to the advancement of science through content sharing capabilities, LabRoots is a powerful advocate in amplifying global networks and communities. Founded in 2008, LabRoots emphasizes digital innovation in scientific collaboration and learning, and is a primary source for current scientific news, webinars, virtual conferences, and more. LabRoots has grown into the world’s largest series of virtual events within the Life Sciences and Clinical Diagnostics community.


News Article | August 10, 2017
Site: www.eurekalert.org

OAK RIDGE, Tenn., Aug. 10, 2017 - Four Oak Ridge National Laboratory researchers specializing in nuclear physics, fusion energy, advanced materials and environmental science are among 59 recipients of Department of Energy's Office of Science Early Career Research Program awards. The Early Career Research Program, now in its eighth year, supports the development of individual research programs of outstanding scientists early in their careers and stimulates research careers in the disciplines supported by the DOE Office of Science. The 59 selectees for fiscal year 2017 were chosen based on peer review of about 700 proposals. "Our effectiveness in solving big problems of national importance over the long term relies directly on the vitality of our early-career staff--their creativity, talents and new ideas," ORNL Director Thomas Zacharia said. "DOE's investment in these promising young researchers is a recognition of their talents and evidence of the importance of their work." Kelly Chipps, a Liane B. Russell Fellow working in ORNL's Physics Division, will receive funding for her proposal, "Next-Generation Particle Spectroscopy at FRIB: A Gas Jet Target for Solenoidal Spectrometers," selected by the Office of Nuclear Physics. Her research seeks to study exotic, unstable nuclei and nuclear reactions that power the stars by combining the benefits of the sophisticated state-of-the-art solenoidal spectrometer at Argonne National Laboratory and the Jet Experiments in Nuclear Structure and Astrophysics system developed at ORNL. The project promises to resolve challenges to achieving high-resolution and low-background particle spectroscopy when applied to the Facility for Rare Isotope Beams (FRIB). David Green, of ORNL's Fusion and Materials for Nuclear Systems Division, proposed a project titled, "Scale-Bridging Simulation of Magnetically Confined Fusion Plasmas," which was funded by the Office of Fusion Energy Sciences. Because of the extreme environment within nuclear fusion devices, only so much of the essential physics can be unraveled by a purely experimental approach. Green's research will exploit the coming wave of exascale computing platforms and advanced timescale-bridging methods to simulate a fusion device in hopes of discovering essential fusion reactor physics that cannot be predicted today. Thomas (Zac) Ward's proposal, "Designing Metastability: Coercing Materials to Phase Boundaries," was selected by the Office of Basic Energy Sciences. Ward works in ORNL's Materials Science and Technology Division. His project will apply previously inaccessible structural distortions to single-crystal transition metal oxides to gain deeper fundamental insights into complexity's role in driving functionality. This work may lead to coexisting nanoscale electronic and magnetic phases of varying properties designed into a single crystal wafer. Such a breakthrough would allow for single-chip multifunctionality expected to drive device applications beyond Moore's law. David Weston, of ORNL's Biosciences Division, submitted a proposal titled, "Determining the genetic and environmental factors underlying mutualism within a plant-microbiome system driving nutrient acquisition and exchange," to be funded by the Office of Biological and Environmental Research. He will identify the genes and metabolic functions involved in the exchange of nutrients between certain plants and microbes and study their response to environmental changes in both laboratory and field settings. Deeper fundamental understanding of the symbiotic plant-microbe relationship could reveal pathways to improve bioenergy crop production in nutrient-limiting environments. National lab recipients will receive at least $500,000 per year to cover annual salary plus research expenses over a planned five years. The final details for each project award are subject to final grant and contract negotiations between DOE and the awardees. ORNL is managed by UT-Battelle for the Department of Energy's Office of Science, the single largest supporter of basic research in the physical sciences in the United States. DOE's Office of Science is working to address some of the most pressing challenges of our time. For more information, please visit http://science. .


The results, published today in Nature, show the game-changing potential of X-ray free-electron lasers, or XFELs, for studying RNA, which guides protein manufacturing in the cell, serves as the primary genetic material in retroviruses such as HIV and also plays a role in most forms of cancer. And because this particular type of RNA switch, known as a riboswitch, is found only in bacteria, a deeper understanding of its function may offer a way to turn off protein production and kill harmful germs without causing side effects in the humans they infect. "Previous experiments at SLAC's X-ray laser have studied biological reactions like photosynthesis that are triggered by light. But this is the first to observe one that is triggered by the chemical interaction of two biomolecules in real time and at the atomic scale," said Yun-Xing Wang, a structural biologist at the National Cancer Institute's Center for Cancer Research who led the international research team. "This really demonstrates the unique capability that X-ray free-electron lasers offer that no current technology, or any other technology on the horizon, can do. It's like you have a camera with a very fast shutter speed, so you can catch every move of the biomolecules in action." The experiments were carried out at SLAC's Linac Coherent Light Source (LCLS), a DOE Office of Science User Facility. They are the first to demonstrate how XFELs can take snapshots and potentially make movies of RNA and other biomolecules as they chemically interact - offering glimpses into fundamental workings of the cell that can't be obtained any other way. RNA is a key part of the genetic material in all living cells. It comes in several types that work together to guide the production of proteins by the cell's ribosomes, according to blueprints encoded in DNA. But both DNA and RNA also contain extensive regions that don't code for any protein - the so-called genetic "dark matter." Scientists thought for many years that these regions didn't do anything. Now they know that they play an important role in determining where and when genes turn on and off and otherwise fine-tuning their function. The vast majority of cancers are due to mutations in these non-coding regions, Wang said, so understanding how these regions work is important for cancer research as well as fundamental biology. However, figuring out what the RNA non-coding regions do is difficult. RNA molecules are wobbly and flexible, so it's hard to incorporate them into the large crystals typically needed to study their atomic structure at X-ray light sources. LCLS removes this barrier by allowing scientists to get structural information from much smaller, nanosized crystals, which are much easier to make. Its powerful X-ray laser pulses, a billion times brighter than any available before, are so short that they collect data from each crystal in a few millionths of a billionth of a second, before damage from the X-rays sets in. Wang's team studied a riboswitch from Vibrio vulnificus, a bacterium related to the one that causes cholera. The riboswitch sits in a long strand of messenger RNA (mRNA), which copies DNA's instructions for making a protein so they can be read and carried out by the ribosome. The switch acts like a thermostat that regulates protein production. In this case, the mRNA guides production of a protein that in turn helps to produce a small molecule called adenine. When there is too much adenine in the bacterial cell, adenine molecules enter pockets in the riboswitches and flip the riboswitches into a different shape, and this changes the pace of protein and adenine production. First Stills of an Elegant Film For the LCLS experiments, the researchers made nanocrystals that incorporated millions of copies of the riboswitch and mixed them with a solution containing adenine molecules. Each crystal was so small that adenine could quickly and uniformly penetrate into every corner of it, enter riboswitch pockets and flip them almost instantaneously, as if they were millions of synchronized swimmers executing a single flawless move. The scientists took snapshots of this interaction by hitting the crystals with X-ray laser pulses at carefully timed intervals after the mixing started. This gave them the first glimpse of a fleeting intermediate stage in the process, which occurred 10 seconds in. Separately, they obtained the first images of the riboswitch in its initial, empty-pocket state, and discovered that it existed in two slightly different configurations, only one of which participates in switching. The researchers were surprised to discover that the sudden change in the shape of the riboswitches was so dramatic that it changed the shape of the entire crystal, too. Normally a major change like this would crack the crystal and spoil the experiment. But because these crystals were so small they held together, so the X-ray laser could still get structural information from them. "To me it's still a mystery how the crystal managed to do that," said Soichi Wakatsuki, a professor at SLAC and at the Stanford School of Medicine and head of the lab's Biosciences Division, who was not part of the research team. "This actually opens up a lot of new possibilities and gives us a new way to look at how RNA and proteins interact with small molecules, so this is very exciting." Explore further: Scientists watch bacterial sensor respond to light in real time More information: J. R. Stagno et al, Structures of riboswitch RNA reaction states by mix-and-inject XFEL serial crystallography, Nature (2016). DOI: 10.1038/nature20599


News Article | November 15, 2016
Site: www.sciencedaily.com

Scientists have used the powerful X-ray laser at the Department of Energy's SLAC National Accelerator Laboratory to make the first snapshots of a chemical interaction between two biomolecules -- one that flips an RNA "switch" that regulates production of proteins, the workhorse molecules of life. The results, published today in Nature, show the game-changing potential of X-ray free-electron lasers, or XFELs, for studying RNA, which guides protein manufacturing in the cell, serves as the primary genetic material in retroviruses such as HIV and also plays a role in most forms of cancer. And because this particular type of RNA switch, known as a riboswitch, is found only in bacteria, a deeper understanding of its function may offer a way to turn off protein production and kill harmful germs without causing side effects in the humans they infect. "Previous experiments at SLAC's X-ray laser have studied biological reactions like photosynthesis that are triggered by light. But this is the first to observe one that is triggered by the chemical interaction of two biomolecules in real time and at the atomic scale," said Yun-Xing Wang, a structural biologist at the National Cancer Institute's Center for Cancer Research who led the international research team. "This really demonstrates the unique capability that X-ray free-electron lasers offer that no current technology, or any other technology on the horizon, can do. It's like you have a camera with a very fast shutter speed, so you can catch every move of the biomolecules in action." The experiments were carried out at SLAC's Linac Coherent Light Source (LCLS), a DOE Office of Science User Facility. They are the first to demonstrate how XFELs can take snapshots and potentially make movies of RNA and other biomolecules as they chemically interact -- offering glimpses into fundamental workings of the cell that can't be obtained any other way. RNA is a key part of the genetic material in all living cells. It comes in several types that work together to guide the production of proteins by the cell's ribosomes, according to blueprints encoded in DNA. But both DNA and RNA also contain extensive regions that don't code for any protein -- the so-called genetic "dark matter." Scientists thought for many years that these regions didn't do anything. Now they know that they play an important role in determining where and when genes turn on and off and otherwise fine-tuning their function. The vast majority of cancers are due to mutations in these non-coding regions, Wang said, so understanding how these regions work is important for cancer research as well as fundamental biology. However, figuring out what the RNA non-coding regions do is difficult. RNA molecules are wobbly and flexible, so it's hard to incorporate them into the large crystals typically needed to study their atomic structure at X-ray light sources. LCLS removes this barrier by allowing scientists to get structural information from much smaller, nanosized crystals, which are much easier to make. Its powerful X-ray laser pulses, a billion times brighter than any available before, are so short that they collect data from each crystal in a few millionths of a billionth of a second, before damage from the X-rays sets in. Wang's team studied a riboswitch from Vibrio vulnificus, a bacterium related to the one that causes cholera. The riboswitch sits in a long strand of messenger RNA (mRNA), which copies DNA's instructions for making a protein so they can be read and carried out by the ribosome. The switch acts like a thermostat that regulates protein production. In this case, the mRNA guides production of a protein that in turn helps to produce a small molecule called adenine. When there is too much adenine in the bacterial cell, adenine molecules enter pockets in the riboswitches and flip the riboswitches into a different shape, and this changes the pace of protein and adenine production. First Stills of an Elegant Film For the LCLS experiments, the researchers made nanocrystals that incorporated millions of copies of the riboswitch and mixed them with a solution containing adenine molecules. Each crystal was so small that adenine could quickly and uniformly penetrate into every corner of it, enter riboswitch pockets and flip them almost instantaneously, as if they were millions of synchronized swimmers executing a single flawless move. The scientists took snapshots of this interaction by hitting the crystals with X-ray laser pulses at carefully timed intervals after the mixing started. This gave them the first glimpse of a fleeting intermediate stage in the process, which occurred 10 seconds in. Separately, they obtained the first images of the riboswitch in its initial, empty-pocket state, and discovered that it existed in two slightly different configurations, only one of which participates in switching. The researchers were surprised to discover that the sudden change in the shape of the riboswitches was so dramatic that it changed the shape of the entire crystal, too. Normally a major change like this would crack the crystal and spoil the experiment. But because these crystals were so small they held together, so the X-ray laser could still get structural information from them. "To me it's still a mystery how the crystal managed to do that," said Soichi Wakatsuki, a professor at SLAC and at the Stanford School of Medicine and head of the lab's Biosciences Division, who was not part of the research team. "This actually opens up a lot of new possibilities and gives us a new way to look at how RNA and proteins interact with small molecules, so this is very exciting."


News Article | November 14, 2016
Site: www.eurekalert.org

Menlo Park, Calif. -- Scientists have used the powerful X-ray laser at the Department of Energy's SLAC National Accelerator Laboratory to make the first snapshots of a chemical interaction between two biomolecules - one that flips an RNA "switch" that regulates production of proteins, the workhorse molecules of life. The results, published today in Nature, show the game-changing potential of X-ray free-electron lasers, or XFELs, for studying RNA, which guides protein manufacturing in the cell, serves as the primary genetic material in retroviruses such as HIV and also plays a role in most forms of cancer. And because this particular type of RNA switch, known as a riboswitch, is found only in bacteria, a deeper understanding of its function may offer a way to turn off protein production and kill harmful germs without causing side effects in the humans they infect. "Previous experiments at SLAC's X-ray laser have studied biological reactions like photosynthesis that are triggered by light. But this is the first to observe one that is triggered by the chemical interaction of two biomolecules in real time and at the atomic scale," said Yun-Xing Wang, a structural biologist at the National Cancer Institute's Center for Cancer Research who led the international research team. "This really demonstrates the unique capability that X-ray free-electron lasers offer that no current technology, or any other technology on the horizon, can do. It's like you have a camera with a very fast shutter speed, so you can catch every move of the biomolecules in action." The experiments were carried out at SLAC's Linac Coherent Light Source (LCLS), a DOE Office of Science User Facility. They are the first to demonstrate how XFELs can take snapshots and potentially make movies of RNA and other biomolecules as they chemically interact - offering glimpses into fundamental workings of the cell that can't be obtained any other way. RNA is a key part of the genetic material in all living cells. It comes in several types that work together to guide the production of proteins by the cell's ribosomes, according to blueprints encoded in DNA. But both DNA and RNA also contain extensive regions that don't code for any protein - the so-called genetic "dark matter." Scientists thought for many years that these regions didn't do anything. Now they know that they play an important role in determining where and when genes turn on and off and otherwise fine-tuning their function. The vast majority of cancers are due to mutations in these non-coding regions, Wang said, so understanding how these regions work is important for cancer research as well as fundamental biology. However, figuring out what the RNA non-coding regions do is difficult. RNA molecules are wobbly and flexible, so it's hard to incorporate them into the large crystals typically needed to study their atomic structure at X-ray light sources. LCLS removes this barrier by allowing scientists to get structural information from much smaller, nanosized crystals, which are much easier to make. Its powerful X-ray laser pulses, a billion times brighter than any available before, are so short that they collect data from each crystal in a few millionths of a billionth of a second, before damage from the X-rays sets in. Wang's team studied a riboswitch from Vibrio vulnificus, a bacterium related to the one that causes cholera. The riboswitch sits in a long strand of messenger RNA (mRNA), which copies DNA's instructions for making a protein so they can be read and carried out by the ribosome. The switch acts like a thermostat that regulates protein production. In this case, the mRNA guides production of a protein that in turn helps to produce a small molecule called adenine. When there is too much adenine in the bacterial cell, adenine molecules enter pockets in the riboswitches and flip the riboswitches into a different shape, and this changes the pace of protein and adenine production. First Stills of an Elegant Film For the LCLS experiments, the researchers made nanocrystals that incorporated millions of copies of the riboswitch and mixed them with a solution containing adenine molecules. Each crystal was so small that adenine could quickly and uniformly penetrate into every corner of it, enter riboswitch pockets and flip them almost instantaneously, as if they were millions of synchronized swimmers executing a single flawless move. The scientists took snapshots of this interaction by hitting the crystals with X-ray laser pulses at carefully timed intervals after the mixing started. This gave them the first glimpse of a fleeting intermediate stage in the process, which occurred 10 seconds in. Separately, they obtained the first images of the riboswitch in its initial, empty-pocket state, and discovered that it existed in two slightly different configurations, only one of which participates in switching. The researchers were surprised to discover that the sudden change in the shape of the riboswitches was so dramatic that it changed the shape of the entire crystal, too. Normally a major change like this would crack the crystal and spoil the experiment. But because these crystals were so small they held together, so the X-ray laser could still get structural information from them. "To me it's still a mystery how the crystal managed to do that," said Soichi Wakatsuki, a professor at SLAC and at the Stanford School of Medicine and head of the lab's Biosciences Division, who was not part of the research team. "This actually opens up a lot of new possibilities and gives us a new way to look at how RNA and proteins interact with small molecules, so this is very exciting." In addition to the National Cancer Institute and SLAC's LCLS, scientists contributing to the research came from Arizona State University, Johns Hopkins University, the Center for Free-Electron Laser Science at Deutsches Elektronen-Synchrotron (DESY), University of Hamburg, Hauptmann-Woodward Medical Research Institute, the National Institutes of Health and the DOE's Argonne National Laboratory. Funding came from the National Science Foundation and the NIH Intramural Research Programs. SLAC is a multi-program laboratory exploring frontier questions in photon science, astrophysics, particle physics and accelerator research. Located in Menlo Park, California, SLAC is operated by Stanford University for the U.S. Department of Energy Office of Science. To learn more, please visit http://www. . SLAC National Accelerator Laboratory is supported by the Office of Science of the U.S. Department of Energy. The 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, please visit science.energy.gov.


Even if a guest walked into the kitchen and held their breath, they still would slough off 10 million bacterial cells in just 60 minutes through skin shed. While the idea may seem revolting, Jack A. Gilbert, UChicago associate professor in ecology & evolution and group leader for microbial ecology in the Biosciences Division at the U.S. Department of Energy's Argonne National Laboratory, assures us it's not. "Nearly all of the germs graciously donated by our friends and family are not disgusting," said Gilbert, who has made a career of exploring how microbial communities assemble themselves in natural and man-made environments. "They are probably good for us in many different ways." Gilbert said our over-sanitized environment may ultimately leave us weaker than our ancestors, who were agrarian and were constantly surrounded by a wide variety of plants and animals. Their bodies adapted to such changes—and so our bodies expect to encounter them, too, he said. "Our ancestors experienced many different types of bacteria on a regular basis," he said. "When you live with such rich biodiversity, the body expects to see it and when it doesn't, it freaks out, which is why we are seeing an explosion in allergies, asthma and hay fever. Our bodies are overreacting to the absence of these organisms." Our constant hand washing—though it might prevent a nasty flu—might also keep us from developing immunities. "We have done a really good job at keeping the bad bugs at bay," Gilbert said, "but we've failed at keeping in those that we need because we live an indoor, sedentary lifestyle." Inviting friends and family to come around on a regular basis may help stimulate our immune systems, he said. Likewise, having very young children interact with a wide variety of animals is only beneficial to their health and greatly outweighs the slim chance of exposure to something harmful, he said. In fact, Gilbert believes some of the social rituals we carry out today—hand shaking, hugging, kissing—may have evolved over millennia as a way to share, spread and develop immunities to bacteria. Kissing, for example, may promote healthy digestion, train the immune system and may even lead to better cognition, Gilbert said. Germs are so prevalent and impossible to eliminate, Gilbert said, there is no need to go overboard scrubbing the house after holiday gatherings. "I would say there is no real reason to increase cleanliness protocols in your property unless one of your guests is really sick, in which case you can isolate them—or tell them not to come over at all," he said.


News Article | January 4, 2016
Site: www.rdmag.com

Lives of soldiers and others injured in remote locations could be saved with a cell-free protein synthesis system developed at the Department of Energy's Oak Ridge National Laboratory. The device, a creation of a team led by Andrea Timm and Scott Retterer of the lab's Biosciences Division, uses microfabricated bioreactors to facilitate the on-demand production of therapeutic proteins for medicines and biopharmaceuticals. Making these miniature factories cell-free, which eliminates the maintenance of a living system, simplifies the process and lowers cost. "With this approach, we can produce more protein faster, making our technology ideal for point-of-care use," Retterer said. "The fact it's cell-free reduces the infrastructure needed to produce the protein and opens the possibility of creating proteins when and where you need them, bypassing the challenge of keeping the proteins cold during shipment and storage." ORNL's bioreactor features elegance through a permeable nanoporous membrane and serpentine design fabricated using a combination of electron beam and photolithography and advanced material deposition processes. This design enables prolonged cell-free reactions for efficient production of proteins, making it easily adaptable for use in isolated locations and at disaster sites. From a functional perspective, the design uses long serpentine channels integrated in a way to allow the exchange of materials between parallel reactor and feeder channels. With this approach, the team can control the exchange of metabolites, energy and species that inhibit production of the desired protein. Through other design features, researchers extend reaction times and improve yields. "We show that the microscale bioreactor design produces higher protein yields than conventional tube-based batch formats and that product yields can be dramatically improved by facilitating small molecule exchange with the dual-channel bioreactor," the authors wrote in their paper, published in the journal Small. The researchers also note that on-demand biologic synthesis would aid the production of drugs that are costly to mass-produce, including orphan drugs and personalized medicines.


News Article | December 29, 2015
Site: phys.org

The device, a creation of a team led by Andrea Timm and Scott Retterer of the lab's Biosciences Division, uses microfabricated bioreactors to facilitate the on-demand production of therapeutic proteins for medicines and biopharmaceuticals. Making these miniature factories cell-free, which eliminates the maintenance of a living system, simplifies the process and lowers cost. "With this approach, we can produce more protein faster, making our technology ideal for point-of-care use," Retterer said. "The fact it's cell-free reduces the infrastructure needed to produce the protein and opens the possibility of creating proteins when and where you need them, bypassing the challenge of keeping the proteins cold during shipment and storage." ORNL's bioreactor features elegance through a permeable nanoporous membrane and serpentine design fabricated using a combination of electron beam and photolithography and advanced material deposition processes. This design enables prolonged cell-free reactions for efficient production of proteins, making it easily adaptable for use in isolated locations and at disaster sites. From a functional perspective, the design uses long serpentine channels integrated in a way to allow the exchange of materials between parallel reactor and feeder channels. With this approach, the team can control the exchange of metabolites, energy and species that inhibit production of the desired protein. Through other design features, researchers extend reaction times and improve yields. "We show that the microscale bioreactor design produces higher protein yields than conventional tube-based batch formats and that product yields can be dramatically improved by facilitating small molecule exchange with the dual-channel bioreactor," the authors wrote in their paper, published in the journal Small. The researchers also note that on-demand biologic synthesis would aid the production of drugs that are costly to mass-produce, including orphan drugs and personalized medicines. Explore further: Biomolecules for the production line More information: Towards Microfluidic Reactors for Cell-Free Protein Synthesis at the Point-of-Care, Small, 2015.

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