Tagged: SLAC SSRL Toggle Comment Threads | Keyboard Shortcuts

  • richardmitnick 4:23 am on February 19, 2015 Permalink | Reply
    Tags: , , , SLAC SSRL   

    From SLAC: “Semiconductor Works Better when Hitched to Graphene” 


    SLAC Lab

    February 18, 2015

    Experiments at SLAC Show Potential for Graphene-based Organic Electronic Devices

    Graphene – a one-atom-thick sheet of carbon with highly desirable electrical properties, flexibility and strength – shows great promise for future electronics, advanced solar cells, protective coatings and other uses, and combining it with other materials could extend its range even further.

    Experiments at the Department of Energy’s SLAC National Accelerator Laboratory looked at the properties of materials that combine graphene with a common type of semiconducting polymer. They found that a thin film of the polymer transported electric charge even better when grown on a single layer of graphene than it does when placed on a thin layer of silicon.

    1
    A material made of semiconducting polymer placed on top of graphene conducts electric charge extremely well and may enable new electronic devices. This work was featured on the cover of the journal Advanced Functional Materials. (David Barbero)

    “Our results are among the first to measure the charge transport in these materials in the vertical direction – the direction that charge travels in organic photovoltaic devices like solar cells or in light-emitting diodes,” said David Barbero of Umeå University in Sweden, leader of the international research team that performed the experiments at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL), a DOE Office of Science User Facility. “The result was somewhat expected, because graphene and silicon have different crystalline structures and electrical properties.”

    But the team also discovered something very unexpected, he said.

    Although it was widely believed that a thinner polymer film should enable electrons to travel faster and more efficiently than a thicker film, Barbero and his team discovered that a polymer film about 50 nanometers thick conducted charge about 50 times better when deposited on graphene than the same film about 10 nanometers thick.

    2
    Studies conducted at the Stanford Synchrotron Radiation Lightsource revealed that when deposited atop graphene, a thicker polymer film (top) conducted charge significantly better than a thinner polymer film (bottom). This is likely because the orientation of the polymer crystallites within the thick film allows the formation of a continuous pathway for the charge to flow. (David Barbero)

    The team concluded that the thicker film’s structure, which consists of a mosaic of crystallites oriented at different angles, likely forms a continuous pathway of interconnected crystals. This, they theorize, allows for easier charge transport than in a regular thin film, whose thin, plate-like crystal structures are oriented parallel to the graphene layer.

    By better controlling the thickness and crystalline structure of the semiconducting film, it may be possible to design even more efficient graphene-based organic electronic devices.

    “The fields most likely to benefit from this work are probably next-generation photovoltaic devices and flexible electronic devices,” said Barbero. “Because graphene is thin, lightweight and flexible, there are a number of potential applications.”

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    SLAC Campus
    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 DOE’s Office of Science.
    i1

     
  • richardmitnick 5:32 pm on February 13, 2015 Permalink | Reply
    Tags: , , , , SLAC SSRL, ,   

    From SLAC: “Scientists Get First Glimpse of a Chemical Bond Being Born” 


    SLAC Lab

    February 12, 2015

    Scientists have used an X-ray laser at the Department of Energy’s SLAC National Accelerator Laboratory to get the first glimpse of the transition state where two atoms begin to form a weak bond on the way to becoming a molecule.

    1
    This illustration shows atoms forming a tentative bond, a moment captured for the first time in experiments with an X-ray laser at SLAC National Accelerator Laboratory. The reactants are a carbon monoxide molecule, left, made of a carbon atom (black) and an oxygen atom (red), and a single atom of oxygen, just to the right of it. They are attached to the surface of a ruthenium catalyst, which holds them close to each other so they can react more easily. When hit with an optical laser pulse, the reactants vibrate and bump into each other, and the carbon atom forms a transitional bond with the lone oxygen, center. The resulting carbon dioxide molecule detaches and floats away, upper right. The Linac Coherent Light Source (LCLS) X-ray laser probed the reaction as it proceeded and allowed the movie to be created. (SLAC National Accelerator Laboratory)

    This fundamental advance, reported Feb. 12 in Science Express and long thought impossible, will have a profound impact on the understanding of how chemical reactions take place and on efforts to design reactions that generate energy, create new products and fertilize crops more efficiently.

    “This is the very core of all chemistry. It’s what we consider a Holy Grail, because it controls chemical reactivity,” said Anders Nilsson, a professor at the SLAC/Stanford SUNCAT Center for Interface Science and Catalysis and at Stockholm University who led the research. “But because so few molecules inhabit this transition state at any given moment, no one thought we’d ever be able to see it.”


    Anders Nilsson, a professor at SLAC and at Stockholm University, explains how scientists used an X-ray laser to watch atoms form a tentative bond, and why that’s important.

    The experiments took place at SLAC’s Linac Coherent Light Source (LCLS), a DOE Office of Science User Facility. Its brilliant, strobe-like X-ray laser pulses are short enough to illuminate atoms and molecules and fast enough to watch chemical reactions unfold in a way never possible before.

    Researchers used LCLS to study the same reaction that neutralizes carbon monoxide (CO) from car exhaust in a catalytic converter. The reaction takes place on the surface of a catalyst, which grabs CO and oxygen atoms and holds them next to each other so they pair up more easily to form carbon dioxide.

    In the SLAC experiments, researchers attached CO and oxygen atoms to the surface of a ruthenium catalyst and got reactions going with a pulse from an optical laser. The pulse heated the catalyst to 2,000 kelvins – more than 3,000 degrees Fahrenheit – and set the attached chemicals vibrating, greatly increasing the chance that they would knock into each other and connect.

    The team was able to observe this process with X-ray laser pulses from LCLS, which detected changes in the arrangement of the atoms’ electrons – subtle signs of bond formation – that occurred in mere femtoseconds, or quadrillionths of a second.

    “First the oxygen atoms get activated, and a little later the carbon monoxide gets activated,” Nilsson said. “They start to vibrate, move around a little bit. Then, after about a trillionth of a second, they start to collide and form these transition states.”

    ‘Rolling Marbles Uphill’

    The researchers were surprised to see so many of the reactants enter the transition state – and equally surprised to discover that only a small fraction of them go on to form stable carbon dioxide. The rest break apart again.

    “It’s as if you are rolling marbles up a hill, and most of the marbles that make it to the top roll back down again,” Nilsson said. “What we are seeing is that many attempts are made, but very few reactions continue to the final product. We have a lot to do to understand in detail what we have seen here.”

    Theory played a key role in the experiments, allowing the team to predict what would happen and get a good idea of what to look for. “This is a super-interesting avenue for theoretical chemists. It’s going to open up a completely new field,” said report co-author Frank Abild-Pedersen of SLAC and SUNCAT.

    A team led by Associate Professor Henrik Öström at Stockholm University did initial studies of how to trigger the reactions with the optical laser. Theoretical spectra were computed under the leadership of Stockholm Professor Lars G.M. Pettersson, a longtime collaborator with Nilsson.

    Preliminary experiments at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL), another DOE Office of Science User Facility, also proved crucial. Led by SSRL’s Hirohito Ogasawara and SUNCAT’s Jerry LaRue, they measured the characteristics of the chemical reactants with an intense X-ray beam so researchers would be sure to identify everything correctly at the LCLS, where beam time is much more scarce. “Without SSRL this would not have worked,” Nilsson said.

    The team is already starting to measure transition states in other catalytic reactions that generate chemicals important to industry.

    “This is extremely important, as it provides insight into the scientific basis for rules that allow us to design new catalysts,” said SUNCAT Director and co-author Jens Nørskov.

    Researchers from LCLS, Helmholtz-Zentrum Berlin for Materials and Energy, University of Hamburg, Center for Free Electron Laser Science, University of Potsdam, Fritz-Haber Institute of the Max Planck Society, DESY and University of Liverpool also contributed to the research. The research was funded by the DOE Office of Science, the Swedish National Research Council, the Knut and Alice Wallenberg Foundation, the Volkswagen Foundation and the German Research Foundation (DFG) Center for Ultrafast Imaging.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    SLAC Campus
    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 DOE’s Office of Science.
    i1

     
  • richardmitnick 5:18 am on February 4, 2015 Permalink | Reply
    Tags: , , , SLAC SSRL   

    From SLAC: “Record Keeping Helps Bacteria’s Immune System Fight Invaders” 


    SLAC Lab

    February 3, 2015

    Bacteria have a sophisticated means of defending themselves, and they need it: more viruses infect bacteria than any other biological entity.

    Two experiments undertaken at the Department of Energy’s SLAC National Accelerator Laboratory provide new insight at the heart of bacterial adaptive defenses in a system called CRISPR, short for Clustered Regularly Interspaced Short Palindromic Repeat.

    This portion of bacteria’s immune system works as a record keeper, taking note of attacking viruses’ identities and storing that information by integrating fragments of the virus’ DNA into its own DNA. In this way, CRISPRs maintain genetic records of previously encountered viruses, making it easier for the bacteria’s immune system to send out complexes that destroy viral invaders by identifying and cutting up the recognized DNA sequences.

    The studies published last year in Science not only reveal important information about how bacteria repel attacking viruses, but also could potentially improve the prevention of disease in humans. Researchers are currently studying ways of preventing and treating cystic fibrosis, blood disorders and HIV by harnessing the CRISPR system to replace one version of a gene with another or to add a working copy for a mutated gene.

    Scientists studied one particular CRISPR-associated complex called Cascade using bright X-rays at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL)., a DOE Office of Science User Facility. In the bacteria Escherichia coli, 11 proteins assemble together with an RNA guide that helps Cascade target invading DNA sequences. Once Cascade confirms that the target DNA is from an invader, a molecular signal recruits a nuclease called Cas3 to finish off the invader by chewing it up.

    1`
    An overview of the crystal structure of Cascade, showing each gene in a different color. The red ribbon represents the RNA guide. (Ryan N. Jackson et al.)

    SLAC SSRL TunnelSLAC SSRL

    Previous work by Blake Wiedenheft, the Montana State University assistant professor of microbiology and immunology who led one of the studies, and his colleagues revealed Cascade’s seahorse-shaped architecture, but studies undertaken at SSRL now reveal how all the parts of this machine assemble into a functional surveillance machine that patrols the intracellular environment for invading DNA.

    2
    A simplified representation of the Cascade RNA guide (green) forming an under-wound ribbon-like structure with invading viral DNA (orange). (Scott Bailey et al.)

    “Determining high-resolution structures of large macromolecules remains challenging,” Wiedenheft said. “Several technical aspects of SSRL, including intensity of light, ability to focus the beam, and shutterless X-ray detector made these results possible.”

    The studies also revealed that Cascade’s RNA guide does not twist together with the viral DNA to form a helix, as was expected. Instead, they form an under-wound ribbon-like structure.

    “A high-resolution structure is essentially a molecular blueprint of a biological machine,” said Wiedenheft. Determining the structure of this complex “is a technical accomplishment that provides the first molecular explanation of how all the parts assemble into a functional surveillance machine.”

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    SLAC Campus
    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 DOE’s Office of Science.
    i1

     
  • richardmitnick 4:27 pm on January 29, 2015 Permalink | Reply
    Tags: , , SLAC SSRL   

    From SLAC: “X-ray Study Reveals Division of Labor in Cell Health Protein” 


    SLAC Lab

    January 28, 2015
    Identical Substructures in ‘TH Protein’ Couple Two Crucial Cellular Functions

    1
    A recent study performed in part at SLAC’s SSRL X-ray facility has provided new insights into how the critical mitochondrial enzyme transhydrogenase, or TH, works in a key process that maintains healthy cells. The crystal structure of TH shows two copies of the molecule (left and right), each of which contains three domains (I, II, III). Structural asymmetry is observed for domain III: One of the structures is facing up (green) to catalyze the production of NADPH from its precursor (black spheres); the other is facing down (magenta) towards the transmembrane domain II to facilitate the transit of a proton. Labels “in” and “out” denote the mitochondrial matrix and the space outside the inner mitochondrial membrane, respectively. (C. David Stout/The Scripps Research Institute)

    Researchers working in part at the Department of Energy’s SLAC National Accelerator Laboratory have discovered that a key protein for cell health, which has recently been linked to diabetes, cancer and other diseases, can multitask by having two identical protein parts divide labor.

    The TH enzyme, short for transhydrogenase, is a crucial protein for most forms of life. In humans and other higher organisms, it works within mitochondria – tiny, double-hulled oxygen reactors inside cells that help power most cellular processes.

    “Despite its importance, TH has been one of the least studied mitochondrial enzymes,” said C. David Stout, a scientist at The Scripps Research Institute whose group led the research. The new study, published Jan. 9 in Science, is an important step toward understanding how this protein manages to perform two crucial cellular tasks at the same time.

    Two Crucial Processes

    As a mitochondrion burns oxygen, it pumps protons out of its innermost compartment, or matrix. Part of the TH protein extends through the membrane that surrounds the matrix; it allows a one-by-one flow of protons back through the membrane. This proton influx, in turn, is linked to the production of NADPH, a compound crucial for defusing oxygen radicals that are harmful to cells.

    But how do TH enzymes couple proton transport and NADPH production? Although Stout’s laboratory and others have previously described portions of the TH enzyme that protrude from the membrane into the mitochondrial matrix, a precise understanding of TH’s mechanism has been elusive. The enzyme has an exceptionally loose structure that makes it hard to evaluate by X-ray crystallography, the standard tool for determining structures of large proteins.

    “Key details we’ve been lacking include the structure of TH’s transmembrane portion, and the way in which the parts assemble into the whole enzyme,” said Josephine H. Leung, a graduate student in the Stout laboratory who was the lead author of the new study.

    For the first time, the team was now able to determine precise details of the transmembrane portion using X-rays from SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) and Argonne National Laboratory’s Advanced Photon Source (APS), both DOE Office of Science User Facilities. Together with X-ray and electron microscopy data of the whole protein, the study provided major clues as to how TH works.

    SLAC SSRL
    SLAC SSRL

    ANL APS interior

    Flipping Functions

    The analysis revealed that two identical copies of TH are bound together in what is called a dimer, and that one copy appears to be involved in proton transport while the other takes part in NADPH production. “Our new study helps clear up some mysteries – suggesting how the enzyme structure might harness protons and indicating that its two sides are able to alternate functions, always staying in balance,” Stout said.

    Attached to TH’s transmembrane structure, just inside the mitochondrial matrix, is the “domain III” structure, which binds NADPH’s precursor molecule during NADPH synthesis. Previously, scientists did not understand how two such structures could work side by side in the TH dimer and not interfere with each other’s activity.

    The new data suggest that these side-by-side structures are highly flexible and always have different orientations.

    “Our most striking finding was that the two domain III structures are not symmetric – one of them faces up while the other faces down,” said Leung.

    In particular, one of the structures is apparently oriented to catalyze the production of NADPH, while the other is turned towards the membrane, perhaps to facilitate transit of a proton. The new structural model indicates that with each proton transit, the two domain III structures flip and switch their functions. “We suspect that the passage of the proton is what somehow causes this flipping of the domain III structures,” said Leung.

    But much work remains to be done to determine TH’s precise structure and mechanism. For example, the new structural data provide evidence of a likely proton channel in the TH transmembrane region, but show only a closed conformation of that structure. “We suspect that this channel can have another, open conformation that lets the proton pass through, so that’s one of the details we want to study further,” said Leung.

    Research funding for the SSRL Structural Molecular Biology Program was provided by the DOE Office of Biological and Environmental Research and the National Institutes of Health, National Institute of General Medical Sciences.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    SLAC Campus
    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 DOE’s Office of Science.
    i1

     
  • richardmitnick 4:24 pm on December 19, 2014 Permalink | Reply
    Tags: , , , , SLAC SSRL,   

    From SLAC: “First Direct Evidence that a Mysterious Phase of Matter Competes with High-Temperature Superconductivity” 


    SLAC Lab

    December 19, 2014

    SLAC Study Shows “Pseudogap” Phase Hoards Electrons that Might Otherwise Conduct Electricity with 100 Percent Efficiency

    Scientists have found the first direct evidence that a mysterious phase of matter known as the “pseudogap” competes with high-temperature superconductivity, robbing it of electrons that otherwise might pair up to carry current through a material with 100 percent efficiency.

    The result, led by researchers at Stanford University and the Department of Energy’s SLAC National Accelerator Laboratory, is the culmination of 20 years of research aimed at finding out whether the pseudogap helps or hinders superconductivity, which could transform society by making electrical transmission, computing and other areas much more energy efficient.

    2
    This illustration shows the complex relationship between high-temperature superconductivity (SC) and a mysterious phase called the pseudogap (PG). Copper oxide materials become superconducting when an optimal number of electrons are removed, leaving positively charged “holes,” and the material is chilled below a transition temperature (blue curve). This causes remaining electrons (yellow) to pair up and conduct electricity with 100 percent efficiency. Experiments at SLAC have produced the first direct evidence that the pseudogap competes for electrons with superconductivity over a wide range of temperatures at lower hole concentrations (SC+PG). At lower temperatures and higher hole concentrations, superconductivity wins out. (SLAC National Accelerator Laboratory)

    The new study definitively shows that the pseudogap is one of the things that stands in the way of getting superconductors to work at higher temperatures for everyday uses, said lead author Makoto Hashimoto, a staff scientist at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL), the DOE Office of Science User Facility where the experiments were carried out. The results were published in Nature Materials.

    SLAC SSRL
    SSRL

    “Now we have clear, smoking-gun evidence that the pseudogap phase competes with and suppresses superconductivity,” Hashimoto said. “If we can somehow remove this competition, or handle it better, we may be able to raise the operating temperatures of these superconductors.”

    Tracking Down Electrons

    In the experiments, researchers used a technique called angle-resolved photoemission spectroscopy, or ARPES, to knock electrons out of a copper oxide material, one of a handful of materials that superconduct at relatively high temperatures – although they still have to be chilled to at least minus 135 degrees Celsius.

    Plotting the energies and momenta of the ejected electrons tells researchers how they were behaving when they were inside the material. In metals, for instance, electrons freely flow around and between atoms. In insulators, they stick close to their home atoms. And in superconductors, electrons leave their usual positions and pair up to conduct electricity with zero resistance and 100 percent efficiency; the missing electrons leave a characteristic gap in the researchers’ plots.

    But in the mid-1990s, scientists discovered another, puzzling gap in their plots of copper oxide superconductors. This “pseudogap” looked like the one left by superconducting electrons, but it showed up at temperatures too warm for superconductivity to occur. Was it a lead-in to superconducting behavior? A rival state that held superconductivity at bay? Where did it come from? No one knew.

    “It’s a complex, intimate relationship. These two phenomena likely share the same roots but are ultimately antagonistic,” said Zhi-Xun Shen, a professor at SLAC and Stanford and senior author of the study. “When the pseudogap is winning, superconductivity is losing ground.”

    Evidence of Competition

    Shen and his colleagues have been using ARPES to investigate the pseudogap ever since it showed up, refining their techniques over the years to pry more information out of the flying electrons.

    In this latest study, Hashimoto was able to find out exactly what was happening at the moment the material transitioned into a superconducting state. He did this by measuring not only the energies and momenta of the electrons, but the number of electrons coming out of the material with particular energies over a wide range of temperatures, and after the electronic properties of the material had been altered in various ways.

    He discovered clear, strong evidence that at this crucial transition temperature, the pseudogap and superconductivity are competing for electrons. Theoretical calculations by members of the team were able to reproduce this complex relationship.

    “The pseudogap tends to eat away the electrons that want to go into the superconducting state,” explained Thomas Devereaux, a professor at Stanford and SLAC and co-author of the study. “The electrons are busy doing the dance of the pseudogap, and superconductivity is trying to cut in, but the electrons are not letting that happen. Then, as the material goes into the superconducting state, the pseudogap gives up and spits the electrons back out. That’s really the strongest evidence we have that this competition is occurring.”

    Remaining Mysteries

    Scientists still don’t know what causes the pseudogap, Devereaux said: “This remains one of the most important questions in the field, because it’s clearly preventing superconductors from working at even higher temperatures, and we don’t know why.”

    But the results pave new directions for further research, the scientists said.

    “Now we can model the competition between the pseudogap and superconductivity from the theoretical side, which was not possible before,” Hashimoto said. “We can use simulations to reproduce the kinds of features we have seen, and change the variables within those simulations to try to pin down what the pseudogap is.”

    He added, “Competition may be only one aspect of the relationship between the two states. There may be more profound questions – for example, whether the pseudogap is necessary for superconductivity to occur.”

    In addition to SLAC and Stanford, researchers from Lawrence Berkeley National Laboratory, Osaka University, the National Institute of Advanced Industrial Science and Technology in Japan, the Japan Atomic Energy Agency, Tokyo Institute of Technology, University of Tokyo and Cornell University contributed to the study. The research was supported by the DOE Office of Science.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    SLAC Campus
    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 DOE’s Office of Science.
    i1

     
  • richardmitnick 5:52 pm on December 8, 2014 Permalink | Reply
    Tags: , , Flu Viruses, , SLAC SSRL   

    From SLAC: “Study May Help Slow the Spread of Flu” 


    SLAC Lab

    December 8, 2014

    X-rays Show How Flu Antibody Binds to Viruses

    An important study conducted in part at the Department of Energy’s SLAC National Accelerator Laboratory may lead to new, more effective vaccines and medicines by revealing detailed information about how a flu antibody binds to a wide variety of flu viruses.

    f
    A false color image of an influenza virus particle, or “virion.” (Centers for Disease Control/Cynthia Goldsmith)

    The flu virus infects millions of people each year. While for most this results in an unproductive and uncomfortable week or two, the flu also contributes to many deaths in the average flu season. And while vaccines are effective in preventing the flu, they require almost yearly reformulation to keep up with the constantly changing virus.

    A team of researchers from The Scripps Research Institute, Fujita Health University and Osaka University studied both samples of flu virus components and an anti-flu antibody. The antibody, called F045-092, was already known to neutralize the flu by connecting to the region of the flu virus that binds to host cells, so it can no longer bind to its target and cause infection.

    f
    Top: The antibody F045-092 inserts a loop (purple) into the region of the flu virus (blue) that would otherwise bind to host cells to initiate infection. With the antibody connected, the flu virus is unable to bind to its target and cannot cause infection. Bottom: Without the antibody present, the flu virus (blue) binds to a host cell receptor (yellow). (Peter Lee et al.)

    “There are patches of the virus that are more hypervariable than others,” said Peter Lee, a postdoctoral research associate at The Scripps Research Institute and first author of the paper. “But the flu always binds to host cells within the same region, and so that binding site needs to be functionally conserved. That makes it a site of vulnerability.”

    The team used the X-ray beams at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) and Argonne National Laboratory’s Advanced Photon Source (APS), both DOE Office of Science User Facilities, to view the structure of the antibody bound to one subtype of the flu virus called H3N2. They discovered that the antibody inserts a loop into the binding site of the virus, which would otherwise attach to a receptor in a host cell. Additional experimental data showed that F045-092 binds a wide variety of strains and subtypes, including all H3 avian and human viruses from 1963 to 2011 that were tested.

    SLAC SSRL
    SSRL at SLAC

    ANL APS interior
    Argonne National Laboratory’s Advanced Photon Source

    This understanding of the antibody’s structural details and binding modes offers new insight for future structure-based drug discovery and novel avenues for designing future vaccines.

    But the only way to achieve those goals is for many groups of scientists to work together, Lee said. “Our lab is very focused on the structure of the virus and antibodies, while there are lots of other labs focused on everything from small protein design to vaccine design,” he said. “Hopefully we can use this structural information and join together as one big team to tackle the flu.”

    SSRL’s Structural Molecular Biology program is supported by the National Institutes of Health and the Office of Biological and Environmental Research of the U.S. Department of Energy.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    SLAC Campus
    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 DOE’s Office of Science.
    i1

     
  • richardmitnick 4:40 pm on November 21, 2014 Permalink | Reply
    Tags: , , , , SLAC SSRL,   

    From SLAC: “Robotics Meet X-ray Lasers in Cutting-edge Biology Studies” 


    SLAC Lab

    November 21, 2014

    Platform Brings Speed, Precision in Determining 3-D Structure of Challenging Biological Molecules

    Scientists at the Department of Energy’s SLAC National Accelerator Laboratory are combining the speed and precision of robots with one of the brightest X-ray lasers on the planet for pioneering studies of proteins important to biology and drug discovery.

    The new system uses robotics and other automated components to precisely maneuver delicate samples for study with the X-ray laser pulses at SLAC’s Linac Coherent Light Source (LCLS). This will speed efforts to map the 3-D structures of nanoscale crystallized proteins, which are important for designing targeted drugs and synthesizing natural systems and processes.

    s
    This illustration shows an experimental setup used in crystallography experiments at SLAC’s Linac Coherent Light Source X-ray laser. The drum-shaped container at left stores supercooled crystal samples that are fetched by a robotic arm and delivered to another device, called a goniometer. The goniometer moves individual crystals through the X-ray beam, which travels from the pipe at upper left toward the lower right. A detector, right, captures X-ray diffraction patterns produced as the X-rays pass through the crystal samples. (SLAC National Accelerator Laboratory)

    i
    Equipment used in a highly automated X-ray crystallography system at SLAC’s Linac Coherent Light Source X-ray laser. The metal drum at lower left contains liquid nitrogen for cooling crystallized samples studied with LCLS’s intense X-ray pulses. (SLAC National Accelerator Laboratory)

    SLAC LCLS
    SLAC LCLS

    A New Way to Study Biology

    “This is an efficient, highly reliable and automated way to obtain high-resolution 3-D structural information from small sizes and volumes of samples, and from samples that are too delicate to study using other X-ray sources and techniques,” said Aina Cohen, who oversaw the development of the platform in collaboration with staff at LCLS and at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL), both DOE Office of Science User Facilities.

    SLAC SSRL
    SLAC SSRL

    She is co-leader of the Macromolecular Crystallography group in the Structural Molecular Biology (SMB) program at SSRL, which has used robotic sample-handling systems to run remote-controlled experiments for a decade.

    The new setup at LCLS is described in the Oct. 31 edition of Proceedings of the National Academy of Sciences. It includes a modified version of a “goniometer,” a sample-handling device in use at SSRL and many other synchrotrons, as well as a custom version of an SSRL-designed software package that pinpoints the position of crystals in arrays of samples.

    LCLS, with X-ray pulses a billion times brighter than more conventional sources, has already allowed scientists to explore biological samples too small or fragile to study in detail with other tools. The new system provides added flexibility in the type of samples and sample-holders that can be used in experiments.

    Rather than injecting millions of tiny, randomly tumbling crystallized samples into the path of the pulses in a thin liquid stream – common in biology experiments at LCLS – the goniometer-based system places crystals one at a time into the X-ray pulses. This greatly reduces the number of crystals needed for structural studies on rare and important samples that require a more controlled approach.

    Early Successes

    “This system adapts common synchrotron techniques for use at LCLS, which is very important,” said Henrik Lemke, staff scientist at LCLS. “There is a large community of scientists who are familiar with the goniometer technique.”

    The system has already been used to provide a complete picture of a protein’s structure in about 30 minutes using only five crystallized samples of an enzyme, moved one at a time into the X-rays for a sequence of atomic-scale “snapshots.”

    It has also helped to determine the atomic-scale structures of an oxygen-binding protein found in muscles, and another protein that regulates heart and other muscle and organ functions.

    “We have shown that this system works, and we can further automate it,” Cohen said. “Our goal is to make it easy for everyone to use.”

    Many biological experiments at LCLS are conducted in air-tight chambers. The new setup is designed to work in the open air and can also be used to study room-temperature samples, although most of the samples used in the system so far have been deeply chilled to preserve their structure. One goal is to speed up the system so it delivers samples and measures the resulting diffraction patterns as fast as possible, ideally as fast as LCLS delivers pulses: 120 times a second.

    The goniometer setup is the latest addition to a large toolkit of systems that deliver a variety of samples to the LCLS beam, and a new experimental station called MFX that is planned at LCLS will incorporate a permanent version.

    Team Effort

    Developed through a collaboration of SSRL’s Structural Molecular Biology program and the Stanford University School of Medicine, the LCLS goniometer system reflects increasing cooperation in the science of SSRL and LCLS, Cohen said, drawing upon key areas of expertise for SSRL and the unique capabilities of LCLS. “The combined effort of staff at both experimental facilities was key in this success,” she said.

    In addition to staff at SLAC’s SSRL and LCLS and at Stanford University’s School of Medicine, researchers from SLAC’s Photon Science Directorate, the University of Pittsburgh School of Medicine, Howard Hughes Medical Institute, Montana State University, Lawrence Berkeley National Laboratory and the University of California, San Francisco also participated in this effort.

    The work was supported by the Department of Energy Office of Basic Energy Sciences, the SSRL Structural Molecular Biology Program via the DOE Office of Biological and Environmental Research, and the Biomedical Technology Research Resources program at the National Institute of General Medical Sciences, National Institutes of Health.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    SLAC Campus
    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 DOE’s Office of Science.
    i1

    ScienceSprings relies on technology from

    MAINGEAR computers

    Lenovo
    Lenovo

    Dell
    Dell

     
  • richardmitnick 2:25 pm on November 12, 2014 Permalink | Reply
    Tags: , , , , SLAC SSRL   

    From SLAC: “Study at SLAC Explains Atomic Action in High-Temperature Superconductors “ 


    SLAC Lab

    November 12, 2014

    A study at the Department of Energy’s SLAC National Accelerator Laboratory suggests for the first time how scientists might deliberately engineer superconductors that work at higher temperatures.

    In their report, a team led by SLAC and Stanford University researchers explains why a thin layer of iron selenide superconducts — carries electricity with 100 percent efficiency — at much higher temperatures when placed atop another material, which is called STO for its main ingredients strontium, titanium and oxygen.

    bs
    In this illustration, a single layer of superconducting iron selenide (balls and sticks) has been placed stop another material known as STO for its main ingredients strontium, titanium and oxygen. The STO is shown as blue pyramids, which represent the arrangement of its atoms. A study at SLAC found that when natural vibrations (green glow) from the STO move up into the iron selenide film, electrons in the film (white spheres) can pair up and conduct electricity with 100 percent efficiency at much higher temperatures than before. The results suggest a way to deliberately engineer superconductors that work at even higher temperatures. (SLAC National Accelerator Laboratory)

    side
    This view from the side makes an important point: Putting iron selenide on top of STO enhances its superconductivity only if it’s applied in a single layer (left). When more than one layer is applied, the natural vibrations coming up from the STO layer don’t give electrons the boost of energy they need to pair up and superconduct (right). (SLAC National Accelerator Laboratory)

    These findings, described today in the journal Nature, open a new chapter in the 30-year quest to develop superconductors that operate at room temperature, which could revolutionize society by making virtually everything that runs on electricity much more efficient. Although today’s high-temperature superconductors operate at much warmer temperatures than conventional superconductors do, they still work only when chilled to minus 135 degrees Celsius or below.

    In the new study, the scientists concluded that natural trillion-times-per-second vibrations in the STO travel up into the iron selenide film in distinct packets, like volleys of water droplets shaken off by a wet dog. These vibrations give electrons the energy they need to pair up and superconduct at higher temperatures than they would on their own.

    “Our simulations indicate that this approach – using natural vibrations in one material to boost superconductivity in another – could be used to raise the operating temperature of iron-based superconductors by at least 50 percent,” said Zhi-Xun Shen, a professor at SLAC and Stanford University and senior author of the study.

    While that’s still nowhere close to room temperature, he added, “We now have the first example of a mechanism that could be used to engineer high-temperature superconductors with atom-by-atom control and make them better.”

    Spying on Electrons

    The study probed a happy combination of materials developed two years ago by scientists in China. They discovered that when a single layer of iron selenide film is placed atop STO, its maximum superconducting temperature shoots up from 8 degrees to nearly 77 degrees above absolute zero (minus 196 degrees Celsius).

    While this was a huge and welcome leap, it would be hard to build on this advance without understanding what, exactly, was going on.

    In the new study, SLAC Staff Scientist Rob Moore and Stanford graduate student J.J. Lee and postdoctoral researcher Felix Schmitt built a system for growing iron selenide films just one layer thick on a base of STO.

    The team examined the combined material at SLAC’s Stanford Synchrotron Radiation Lightsource, a DOE Office of Science User Facility. They used an exquisitely sensitive technique called ARPES to measure the energies and momenta of electrons ejected from samples hit with X-ray light. This tells scientists how the electrons inside the sample are behaving; in superconductors they pair up to conduct electricity without resistance. The researchers also got help from theorists who did simulations to help explain what they were seeing.

    SLAC SSRL
    SSRL at SLAC

    A Promising New Direction

    “This is a very impressive experiment, one that would have been very difficult to impossible to do anywhere else,” said Andrew Millis, a theoretical condensed matter physicist at Columbia University, who was not involved in the study. “And it’s clearly telling us something important about why putting one thin layer of iron selenide on this substrate, which everyone thought was inert and boring, changes things so dramatically. It opens lots of interesting questions, and it will definitely stimulate a lot of research.”

    Scientists still don’t know what holds electron pairs together so they can effortlessly carry current in high-temperature superconductors. With no way to deliberately invent new high-temperature superconductors or improve old ones, progress has been slow.

    The new results “point to a new direction that people have not considered before,” Moore said. “They have the potential to really break records in high-temperature superconductivity and give us a new understanding of things we’ve been struggling with for years.”

    He added that SLAC is developing a new X-ray beamline at SSRL with a more advanced ARPES system to create and study these and other exotic materials. “This paper predicts a new pathway to engineering superconductivity in these materials,” Moore said, “and we’re building the tools to do just that.”

    In addition to researchers from SLAC’s Materials Science Division and from Stanford, scientists from the University of British Columbia, the University of Tennessee, Lawrence Berkeley National Laboratory and the University of California, Berkeley contributed to this study. The work was funded by the DOE Office of Science.

    See the full article here.

    SLAC Campus
    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 DOE’s Office of Science.
    i1

    ScienceSprings relies on technology from

    MAINGEAR computers

    Lenovo
    Lenovo

    Dell
    Dell

     
  • richardmitnick 10:18 am on November 11, 2014 Permalink | Reply
    Tags: , , , , SLAC SSRL,   

    From SLAC: “Researchers Take Snapshots of Potential ‘Kill Switch’ for Cancer” 


    SLAC Lab

    November 10, 2014

    X-ray Study Shows Protein Switch for Programmed Cell Death in Motion

    A study conducted in part at the Department of Energy’s SLAC National Accelerator Laboratory has revealed how a key human protein switches from a form that protects cells to a form that kills them – a property that scientists hope to exploit as a “kill switch” for cancer.

    The protein, called cIAP1, shields cells from programmed cell death, or apoptosis – a naturally occurring crackdown on unhealthy cells and tissues. When a cell is in trouble, a signal activates cIAP1, which rapidly transforms into a state that allows apoptosis to take place.

    cell
    The structure of cellular inhibitor-of-apoptosis protein 1 (cIAP1) in its “closed” state. The protein is a key switch for apoptosis, or programmed cell death, and is composed of four distinct domains (color coded) that rearrange depending on the position of the switch. (Allyn Schoeffler/Genentech)

    “Cancer cells produce excess amounts of cIAP1 in an attempt to shut down apoptosis and evade death,” says senior staff scientist Thomas Weiss from SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL), a DOE Office of Science User Facility, who participated in the study. “The search for drugs that would switch apoptosis back on to eradicate cancer is a very active research field.”

    The researchers used X-rays from SSRL to watch in real time how cIAP1 transitions from one state to another. The results are an important step towards becoming able to control the protein’s switching properties.

    “Our study closely ties cIAP1’s motions to its role as a switch,” says Allyn Schoeffler, a senior research associate at Genentech Inc. in South San Francisco and lead author of the study, published Nov. 10 in Nature Structural & Molecular Biology. “We now know why cIAP1 can act as a strictly controlled fail-safe for apoptosis and, at the same time, remain flexible enough to undergo rapid structural transitions.”

    Incomplete Static Model

    Earlier studies had given researchers a fairly good idea of cIAP1’s structure and general mechanism.

    In its “closed” state, which blocks apoptosis, the protein’s four parts, or domains, are tightly bound together in a rather rigid, compact structure.

    When a signal molecule binds to a specific site in cIAP1, the protein changes into its “open” state, in which the domains arrange in a more flexible, linear way. When two identical copies of this open structure partner up in what is known as a dimer, the assembly eventually self-destructs, removing the brake that blocks apoptosis and allowing cellular clean-up to carry on.

    “This model of cIAP1 action has largely been derived from static images of the protein,” Schoeffler says. “However, static pictures do not tell us the whole story.”

    Bringing Motion into the Equation

    To find out more, the research team first used a technique known as nuclear magnetic resonance spectroscopy, or NMR, to analyze how the protein domains move in the closed state, and followed up with studies at SSRL, where they observed how X-rays scatter off the transforming sample.

    scat
    Small-angle X-ray scattering models of different cIAP1 states. In its “closed” state, which blocks apoptosis, the domains are tightly bound together in a compact structure (left). Binding of a signal molecule for apoptosis switches the protein into its “open” state, in which the domains arrange in a more flexible linear way (center). When two identical copies of the open structure partner up in what is known as a dimer (right), the assembly eventually self-destructs, thereby allowing apoptosis to take place. (Allyn Schoeffler/Genentech)

    “The results showed that cIAP1 switches from ‘closed’ to ‘open’ extremely fast, within only 300 milliseconds, which we were able to determine using a technique called time-resolved small-angle X-ray scattering,” says Weiss. “The following dimer formation is even faster than that.”

    open
    Protein envelopes of cIAP1’s “open” and “closed” forms as determined by small-angle X-ray scattering (left) with detailed molecular structures modeled into them (right). For the first time, scientists have now monitored in real time how cIAP1 transitions from one state to another. (Allyn Schoeffler/Genentech)

    In addition, the scientists observed that the protein “breathes” rapidly in its closed form, with interfaces between domains opening and closing quickly.

    “The only region that is relatively rigid is the interaction site for the apoptosis signal,” says Schoeffler. “This well-defined site in the closed state allows nature to control cIAP1 very tightly. It is the critical latch that keeps the switch closed and makes sure that it does not open accidentally.”

    The rest of the protein, in contrast, is very flexible and allows cIAP1 to open instantaneously, like a spring-loaded trigger mechanism, when the proper signal is received. Once the trigger has been pulled, cell death becomes inevitable.

    Ties to Cancer Research

    The new insights could potentially benefit recent developments in cancer research. In fact, several studies are underway to explore the use of synthetic compounds that mimic nature’s signal molecules.

    “Natural and synthetic molecules are thought to interact with this protein the same way,” says Schoeffler. “Therefore, the mechanisms revealed by our study are likely to hold true in medically relevant molecules as well.”

    Research funding for the SSRL Structural Molecular Biology Program was provided by the DOE Office of Biological and Environmental Research and the National Institutes of Health, National Institute of General Medical Sciences.

    See the full article here.

    SLAC Campus
    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 DOE’s Office of Science.
    i1

    ScienceSprings relies on technology from

    MAINGEAR computers

    Lenovo
    Lenovo

    Dell
    Dell

     
  • richardmitnick 7:45 am on October 7, 2014 Permalink | Reply
    Tags: , , SLAC SSRL   

    From SLAC: “Study Reveals ‘Bellhops’ in Cell Walls Can Double as Hormones” 


    SLAC Lab

    October 6, 2014

    Discovery at SLAC’s Synchrotron Could Lead to New Drug Designs, Treatments

    Researchers have discovered that some common messenger molecules in human cells double as hormones when bound to a protein that interacts with DNA. The finding could bring to light a class of previously unknown hormones and lead to new ways to target diseases – including cancers and a host of hormone-related disorders.

    image
    In this rendering, the structure of the nuclear receptor transcription factor Steroidogenic Factor-1 (SF-1, shown in gray) is bound by the signaling phospholipid referred to as “PIP3″ (blue and red). (Raymond Blind/UCSF)

    Published in the Oct. 6 edition of Proceedings of the National Academy of Sciences, these results were made possible, in part, by X-ray experiments at the Department of Energy’s SLAC National Accelerator Laboratory.

    “This finding is comparable in its importance to the discovery of how the estrogen hormone triggers activity in human cells, which was key in the development of anti-breast cancer drugs and other hormone treatments,” Robert Fletterick, professor of biochemistry and biophysics at University of California, San Francisco, and one of the principal investigators in the study, said.

    Resolving a Cellular Mystery

    Researchers focused on messengers called signaling phospholipids that act like bellhops in cell walls, escorting proteins to compartments within a cell and activating their functions. The results could explain why these messengers had been observed linked to proteins in the nucleus of cells; their purpose there had been a mystery.

    pj
    Renderings of a signaling phospholipid, PIP3, which was studied while bound to a nuclear receptor, SF-1. The phospholipid was found to behave as a hormone. (Raymond Blind/UCSF)

    X-ray crystallography at SLAC’s Stanford Synchrotron Radiation Lightsource, a DOE Office of Science User Facility, provided the first detailed look at how this messenger acts as a hormone in binding to a specialized hormone-sensing protein called a nuclear receptor.

    SLAC SSRL
    SLAC SSRL

    These receptors are known to interact with DNA in the cell’s nucleus and directly regulate gene expression – a critical mechanism for carrying out the cell’s functions. The experiment focused on a well-studied receptor called SF-1 because its mutations are believed to be associated with infertility and other reproductive disorders, and diseases including colon and pancreatic cancers.

    In analyzing X-ray data measured at SSRL, researchers observed how the phospholipids act like hormones when docked into the SF-1 receptors. Hormones are key links in the communications chain between different types of cells and organs that turn on specific genes in cells and activate a broad range of responses.

    “The greatest impact of this work might be to prompt scientists to take a new view of phospholipids and what they do in the cell,” said Holly A. Ingraham, a UCSF professor who participated in the study.

    “The idea that a component of a cell membrane such as a phospholipid could work as a hormone, triggering gene expression, is quite novel,” she said. “People have not really known what their role is in the nucleus. Now we can say for the first time we know why they are there: Some of them might be acting like hormones.”

    New Details in Bound Biomolecule

    Ray Blind, a UCSF postdoctoral researcher who led the study, devoted years of effort to finding a way to prepare crystallized samples of two types of phospholipids that were separately bound to the SF-1 receptor. High-quality crystals were needed to capture high-resolution X-ray data of their contents and determine the structure of the biomolecular complexes.

    Debanu Das, a staff scientist at SSRL’s Structural Determination Core of the Joint Center for Structural Genomics, oversaw the experiments at SSRL. Based on highly automated X-ray data collection and analysis of about 250 crystal samples, scientists were able to fully map the 3-D atomic-scale structure of the biomolecules, revealing never-before-seen details.

    Well-known hormones like estrogen and testosterone bind to and activate receptors by changing their shape. The study found that the phospholipids bind with the receptor protein in a more complex way than classic hormones do, which potentially enables the phospholipids to manipulate the shape of receptors in more profound ways.

    The researchers said they hope to design synthetic molecules that can target the disease-associated structures in the receptor protein.

    The Joint Center for Structural Genomics is a research consortium that includes SLAC’s SSRL; The Scripps Research Institute; the Genomics Institute of the Novartis Research Foundation; the University of California, San Diego; and the Sanford-Burnham Medical Research Institute. The joint center is supported by the National Institute of General Medical Sciences’ Protein Structure Initiative (PSI) and the National Institutes of Health. The research was also supported by the PSI-Biology Partnership for Stem Cell Biology. Support for the SSRL Structural Molecular Biology Program, whose X-ray facilities enabled the structural work, is provided by the DOE Office of Biological and Environmental Research and by the National Institute of General Medical Sciences.

    See the full article, with video, here.

    SLAC Campus
    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 DOE’s Office of Science.
    i1

    ScienceSprings relies on technology from

    MAINGEAR computers

    Lenovo
    Lenovo

    Dell
    Dell

     
c
Compose new post
j
Next post/Next comment
k
Previous post/Previous comment
r
Reply
e
Edit
o
Show/Hide comments
t
Go to top
l
Go to login
h
Show/Hide help
shift + esc
Cancel
Follow

Get every new post delivered to your Inbox.

Join 413 other followers

%d bloggers like this: