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ALSNews Features
Synchrotron Science at the AAAS Annual Meeting Print

 

Light sources took center stage at several sessions at the American Association for the Advancement of Science (AAAS) 2016 Annual Meeting in Washington, DC. The meeting's theme of Global Science Engagement lent itself well to the inherently collaborative nature of synchrotron science, which was featured in the following sessions.

 

SESAME: A Scientific Source of Light in the Middle East

SESAME light source.

The third-generation, 2.5-GeV SESAME light source, under construction in Amman, Jordan, is slated to begin commissioning later this year. Introductory remarks by Chris Llewellyn Smith (University of Cambridge), president of the SESAME Council, highlighted the opportunities the project presents for international collaboration and peace building, particularly among its nine Middle Eastern member countries, as well as ongoing challenges SESAME will have to overcome to be successful, including access to solar power to combat rising energy costs. Earlier this month SESAME celebrated the installation of the first of sixteen cells in its storage ring. The session also included talks by SESAME Council Vice President Eliezer Rabinovici (Hebrew University), who discussed the peace-building prospects in more detail; SESAME Scientific Advisory Committee Chair Zehra Sayers (Sabanci University), who detailed the current status of planning for up to 30 beamlines; and SESAME Beamline Scientist Gihan Kamel, who discussed SESAME’s infrared spectroscopy and microspectroscopy beamline, EMIRA.

 

Cleaner Energy Solutions: What Can 21st Century Large-Scale Physics Deliver?

Anke Kaysser-Pyzalla (Helmholtz-Zentrum Berlin) provided an overview of the importance of synchrotron radiation for driving advances in new energy-relevant materials. After highlighting key capabilities synchrotron radiation provides, including identification of elements and chemical states, electronic and magnetic state selectivity, structural selectivity, and temporal sensitivity, she gave specific examples of how synchrotron science is informing organic electronics, perovskite solar cells, gas storage, and battery research. Claire Corkhill (University of Sheffield) discussed the world’s first long-duration x-ray synchrotron experiment, being performed at the UK’s Diamond Light Source. Corkhill’s research investigates changes in cement chemistry and microstructure for nuclear waste immobilization applications. By taking diffraction patterns of the cement every two weeks for two years, she hopes to inform the design of a new cement that will improve the option for geological disposal of the world’s hundreds of thousands of tons (and growing) of radioactive waste material.


Iran: Science Cooperation in a Post-Sanctions Era

Javad Rahighi, director of the Iranian Light Source Facility, provided an update on the plans for Iran’s largest-ever basic science project. The 3-GeV synchrotron is due to start construction in the coming months in Qazvin, just west of Tehran, and is projected to be operational by 2025. Rahighi highlighted the opportunities provided by the July 2015 nuclear agreement between the world powers and Iran. In the post-sanctions era, Iranian scientists have an easier time traveling abroad and sending their students to learn abroad, and the sophisticated scientific equipment necessary to build a light source facility is easier to obtain. In addition, Rahighi is hopeful that better scientific opportunities at home will help combat “brain drain,” keeping Iranian scientists in Iran.

 

Citizen Science and Information Technology: Engaging People for a Better Planet

Carla Gomes, professor of computer science and director of the Institute for Computational Sustainability at Cornell University, reported on the integration of citizen science data (crowdsourced information) with advanced computational techniques to accelerate the interpretation of synchrotron-derived x-ray diffraction data. Gomes used the superior pattern recognition capabilities of citizen scientists to inform computational algorithms programmed to solve the crystal structures of hundreds of points along a ternary thin film composition spread. The data collected from the UDiscoverIt graphical user interface for providing human input to the solving algorithm enabled a significant reduction in the amount of time to solve the crystal structures compared with humans or computers alone. Gomes believes human computation will dramatically speed up the performance of combinatorial optimization methods, accelerating sustainable energy materials discovery.

 
ALS Biosciences Crosscutting Review Print

by Steve Kevan and Corie Ralston

 

The ALS organized and recently held a two-day crosscutting review of its bioscience programs. The ALS Scientific Advisory Committee (SAC) sponsors these reviews, which are intended to evaluate the performance of entire research subdisciplines served by the facility and to motivate strategic thinking about capabilities and research directions that are ripe for future development. SAC member Janet Smith from the University of Michigan chaired the review, and other committee members were Mark Tobin from the Australian Synchrotron, Scott Fraser from University of Southern California, Wayne Hendrickson from Columbia University, and Thomas Weiss from SLAC.

Biosciences beamlines at the ALS.

Research areas covered by the review included macromolecular crystallography and solution scattering, cellular nano-tomography, and infrared microscopy. Talks by staff and 1-2 users of all beamlines in these areas were followed by ample time for discussion. There was also a poster session, at which additional current and planned research and capabilities were presented. An important underlying topic of discussion throughout the review was the planned ALS upgrade for ultrahigh brightness and how it will impact biosciences at the ALS. Overall, the review committee was very pleased by what they saw and provided valuable advice concerning the current ALS bioscience programs and how they might evolve in the future. The committee emphasized the importance of the GEMINI protein micro-crystallography beamline, scheduled for commissioning in 2018 and funded by both the Howard Hughes Medical Institute and industry, and suggested ongoing communication and planning for the ALS bioscience program on ALS-U.

The ALS aims to conduct two programmatic reviews each year and always seeks active user engagement in the planning and execution of these reviews.

 
Call for General User Proposals - Upcoming Deadline Print

 

The User Office is accepting new General User Proposals (GUPs) from scientists who wish to conduct research at the ALS in the 2016-2 July-Dec cycle.

 

PROPOSAL SUBMISSION DEADLINE: March 2, 2016


Please log in to ALSHub to submit a new GUP or to make a Beam Time Request (BTR) on an existing active proposal.

Users are reminded that they need to have an ALSHub account to submit proposals, and that creating an account may take 1-2 business days. We encourage all users to check their account well before the proposal deadline.

 

New Proposals

For more information about how to apply for beam time and proposal writing guidelines, follow the link to Apply for Beamtime in the User Guide.

 

Maintaining an Active Proposal

Proposals for general sciences beamlines are considered active for two years or until the total shifts requested in the proposal have been used. Users may decide whether to submit a new proposal or make a BTR on an active proposal based on the cutoff score for that beamline. Users are reminded that their proposal score may be improved if it fell below the cutoff in the first cycle, as described on GUP web pages.

 

RAPIDD Proposals

Users requiring limited but rapid access to ALS beam time may prefer to submit a RAPIDD proposal rather than a GUP. RAPIDD proposals may be submitted at any time. The system includes:

  • Rapid access to structural biology beamlines
  • Rapid access to some general user beamlines (7.3.3, 8.3.2, and 11.3.1 currently; 7.0.2 Maestro is coming soon)
  • Industry proposals on most ALS-run beamlines
  • Director's discretionary beam time on most ALS-run beamlines

 

Productivity and Past Publications

All proposal forms include a productivity section with publications from previous ALS work. The publications will be pre-filled automatically from the ALS publication database by searching for the principal investigator's name. Submission of publications is via the LBNL reporting system and is now much quicker and easier, based on entering the publication’s DOI. ALS users need to choose the correct entry on the right-hand side list to input publications:

  • LBNL staff should login with their Berkeley Lab Identity
  • ALS users who are not staff should use the ALS User input

A full description of the new system may be found here. Please make sure your publications are entered into our database, and be sure to select your group’s publication when submitting your proposal.

 
ALS "Workhorse" Endstation Retires after 22 Years of Service Print

 

Following a career spanning over two decades, ALS endstation 8.0.1.1 retired last October. The endstation, which specializes in soft x-ray fluorescence, is one of many hosted by Beamline 8.0.1 and has been known as a “workhorse” for the more than 450 peer-reviewed publications to its credit.

Endstation 8.0.1.1 during its heyday, pictured (from left) with scientists
Lin-Wang Wang, Gao Liu, and Wanli Yang. Credit: Roy Kaltschmidt

Its replacement will offer the same techniques—x-ray absorption and x-ray emission spectroscopy—as its retired counterpart but with higher resolution and detection efficiency. “It’s a completely new type of emission spectrometer compared with the previous retired one,” says ALS Beamline Scientist Wanli Yang. “In particular, the new spectrometer is optimized for very high efficiency RIXS [resonant inelastic x-ray scattering].” Thanks to the expertise of ALS scientists Jinghua Guo and Yi-De Chuang, the new system also features options for in situ sample environments that are well suited for studying energy-related devices, like batteries, fuel cells, and catalytic materials, as well as improved resolution and upgraded optics.

Although the distinction of “first light” at the ALS went to endstation 10.3.1 on October 5, 1993, endstation 8.0.1.1 may have been the first ALS experimental system cataloged. Affixed to its frame was a tag with the experiment number “93-002,” from when the endstation was commissioned by Tom Callcott and his group. The ALS experiment database shows endstation 10.3.1 as “93-003.” According to ALS Safety Experiment Coordinator David Malone, there is no record of a “93-001.”

Endstation 8.0.1.1's experiment number tag.

What happens to a retired ALS endstation? The first priority is to redeploy its components at the Lab, including at other ALS endstations. For example, ALS users Clemens Heske and Monika Blum of the University of Nevada, Las Vegas plan to use the old x-ray spectrometer on a roll-up endstation dedicated to x-ray emission. Although the spectrometer’s resolution and efficiency are lower than the new spectrometer, “It’s still a working x-ray emission spectrometer, and for many purposes it’s still useful,” says Yang.

Endstation 8.0.1.1 leaves the ALS in search
of new adventures.

Once ALS users have staked their claims, the parts are offered to other divisions at Berkeley Lab through Procurement and Property Management’s Excess Services. Todd Anderson, the Lab’s excess and off-site storage lead, then posts any remaining components in the federal government’s General Services Administration GSAXcess® database, where federal agencies and registered state and local entities can search for potentially useful property. Anything left at the end of the process is listed by the Lab for public sale bid. “A lot of artists actually like these salvaged parts,” explains Anderson. Components not destined for another facility, project, or piece of art, find new life in other forms through recycling. Almost nothing is sent to the landfill.

While the old endstation 8.0.1.1 components await news of their fates, the new endstation is being tuned and calibrated. Yang expects it to be available to users in February 2016.

 
ALS Director's Update 2016: Reflections on Our Past, Present, and Future Print

 

We entered the new year on a very positive note with the passage of a federal budget for fiscal year 2016 that will provide a modest increase in funding for ALS operations. Another exciting outcome of the budget process was that Congress provided additional funding this year for research and development for the ALS upgrade, ALS-U. We are in the early stages of discussing this potential project with DOE, and in February we will make a presentation to the Basic Energy Sciences Advisory Committee (BESAC) to help gain the support of this very important advisory group. I am very pleased to see gathering momentum for the exciting idea of increasing the brightness of ALS by a thousand times and for all of the new science we will be able to do.

Our new lab director, Mike Witherell, was recently named by the University of California Board of Regents. He is currently the vice chancellor for research at the University of California, Santa Barbara and knows DOE well as he is a former director of Fermilab. Mike will make several visits to LBNL before his starting date of March 1 and has already told me of his strong interest in and support for ALS-U.

ALS Director Roger Falcone takes new LBNL Lab Director Mike Witherell on a tour of the ALS.

Our productivity at ALS continues to be excellent, with continued growth in the number of annual users (now about 2,500) and publications (about 900). We are as busy as ever adding to our scientific capabilities, with many beamline projects nearing completion (e.g., MAESTRO, our photoemission nanoprobe) or under full steam (QERLIN, for inelastic scattering, and AMBER, for renewable energy science). Our partners have generously invested resources to help us complete these and other projects. Those partners include the Gordon and Betty Moore Foundation, Pacific Northwest National Lab, and the Howard Hughes Medical Institute, among many other institutions that are interested in supporting our science and technologies. Our partnerships with all of the Lab’s divisions have never been stronger in jointly supporting existing beamlines and growing new activities. Our new instruments are also well aligned with the science goals for the next decade as outlined in the new DOE BES report, Challenges at the Frontiers of Matter and Energy. Our new instruments are also poised to take full advantage of a future ALS-U.

I am well aware of the need to increase our staffing, both in certain areas of engineering as we increase our effort on ALS-U and work to complete all our beamline projects within the next two to three years, and to support user science at our beamlines. Our plans for new instruments and an upgrade of our facility are very important and exciting, but we need to be realistic about demands on our existing staff’s time. I am working with other divisions at the Lab and our other partners to make sure we get as much support as possible.

We are also beginning to prepare for our next triennial review by DOE, which will take place in spring 2017. These reviews are critical for our future, as we get important feedback on our operations from our sponsors. I am pleased to have the excellent help of our new communications director, Ashley White, who is always available to assist folks throughout the ALS community in creating the right messages for explaining what we do and why we do it!

I am very confident that we are succeeding in our mission, exceeding expectations in providing critical resources to the nation, and supporting users in doing outstanding science in a safe environment. For that success, I want to thank both our exceptional staff and our terrific user community!

 
Notification of General User Proposal and Approved Program Results Print

by Sue Bailey, User Services Group Leader


The Proposal Study Panel (PSP) met on October 23 to oversee and finalize the scoring of General User Proposals for the 2016-1 Feb-June operating cycle and to make recommendations to the ALS Scientific Advisory Committee (SAC) on Approved Program applications. Beam time allocations are completed and users have been notified to view the results by logging in to ALSHub.

Users will need to click on the Experiment ID to view the reviewer comments and to track the beamtime allocated. An example of what you will see is shown below.

Staff in the user office are available throughout this process to answer user queries and help you. Do not hesitate to contact us for advice. If there is no User Agreement in place, please contact user office staff as soon as possible.

 
2015 Director's Awards Print

 

ALS staff took top honors in Lawrence Berkeley National Lab's 2015 Director's Awards for Exceptional Achievement and were recognized in a ceremony earlier this month. The ALS recipients comprised nearly half of this year's awardees, receiving recognition in the scientific, early scientific career, and safety categories. The Director's Awards honor individuals in both the scientific and operations divisions for their high achievement, leadership, collaboration, participation in or support of multidisciplinary science, cross-divisional projects, and commitment to excellence in advancing the Lab's mission and strategic goals.

Clockwise, from top left: Christoph Steier and Arnaud Madur were presented their award by Don DePaolo, Associate Lab Director for Energy Sciences; David Kilcoyne, Rich Celestre, Stefano Marchesini, Tolek Tyliszczak, Tony Warwick, Lee Yang, and David Shapiro (not pictured) were presented their award by James Symons, Associate Lab Director for Physical Sciences; Scott Taylor was presented his award by Glenn Kubiak, Associate Lab Director for Operations and Chief Operating Officer; and Cheng Wang, Eric Schaible, and Alexander Hexemer (not pictured) were presented their award by Kathy Yelick, Associate Lab Director for Computing Sciences. Credit: Roy Kaltschmidt

The Director's Award for Exceptional Scientific Achievement went to two ALS teams:

  • The ALS Brightness Upgrade Team of Christoph Steier and Arnaud Madur, who led the largest improvement of the ALS storage ring since the facility was built in 1993. The brightness improvement enables experiments at the ALS to be done more quickly and with better spatial and spectral resolution.
  • The Development of X-Ray Microscopy at World Record Resolution Team of Rich Celestre, David Kilcoyne, Stefano Marchesini, David Shapiro, Tolek Tyliszczak, Tony Warwick, and Lee Yang, who achieved 3 nm resolution by building a new microscope based on a novel mode of operation called ptychography. This capability is an important tool for energy sciences, as shown in initial work on lithium iron phosphate batteries.

The ALS SAXS-WAXS Team of Alexander Hexemer, Eric Schaible, and Cheng Wang received a Director's Award for Exceptional Early Scientific Career Achievement for building a new beamline devoted to the study of nanoscale systems and developing it into the most productive SAXS-WAXS facility worldwide.

Scott Taylor was honored with the Director's Award for Exceptional Safety Achievement for achieving significant advances in the Lab's safety culture by working to increase the alignment between effective Employee Health and Safety programs and the performance of groundbreaking science.

 
2015 ALS User Meeting Highlights Print

 

The 2015 User Meeting brought together 405 ALS users from around the world, many of whom shared insights and sparked discussion with presentations of their ALS research highlights. UEC Chair Chris Cappa launched the meeting with a welcome, followed by another from Berkeley Lab Director Paul Alivisatos. Speaking of the vitality and community that’s key to the ALS, Alivisatos also touched on how the ALS could be utilized and optimized with a high coherence upgrade. ALS Director Roger Falcone outlined short-term and long-term planning for the ALS, with ongoing efforts to develop new beamlines and capabilities within the next three years and longer-term.

DOE Associate Director of Science for Basic Energy Science (BES), Dr. Harriet Kung, delivered a Washington update, beginning with an acknowledgement that science funding remains challenging, with 2015 marking the third consecutive year that funding has been below request. “We are hoping to rally support to turn the tide around,” Kung said, and encouraged users to get in touch with their elected representatives and express the importance of user facilities and basic research. Kung summarized BES research on future light sources with the statement: “Diffraction-based light sources are the future, and the U.S. has to make an investment.”

The first scientific speaker of the morning, Stanford University’s Gordon Brown, spoke about x-ray spectroscopic, scattering, and imaging studies of earth materials and processes. Brown and his team have used STXM techniques at the ALS to determine various soil characteristics to inform their research on abiotic and biotic crustal nucleation and growth. Brown’s research has also focused on the important role of iron hydroxide nanoparticles in the environment, and their STXM images from the ALS have shown the properties of the iron distribution and organic carbon in mine drainage samples.

John Turner, from the National Renewable Energy Laboratory (NREL), was up next with a lively presentation about semiconductor systems and catalysis for photoelectrochemical (PEC) water splitting. In the search for sustainable paths to hydrogen for fuel, ammonia, and energy storage, economics are the final determination, says Turner, and the cost of hydrogen is mainly determined by the cost of electricity. Turner has focused his research on molecular catalysts for PEC water splitting, in an effort to build higher-efficiency water splitting devices.

Hewlett Packard Research Scientist Stan Williams spoke about the future of transistors and the search for higher resolution in energy, space, and time. He and his research team have turned to the human brain for clues, which has led them to the memristor. The fourth basic circuit element, the memristor (short for “memory resistor”) joins the other passive elements to create a device with the ability to “remember” changes even when it loses power. Williams expressed that the most important thing he and his team bring to HP and the industry at large is modeling. “High quality models enable our circuit designers to actually design accurate circuits,” he says. Williams uses STXM at the ALS to investigate nanodevices, and they need the best possible energy resolution to do this. “Our research at the ALS has led to fundamental materials understanding,” he says.

Longtime ALS user Chuck Fadley, a UC Davis physicist, was up next with a presentation about x-ray optics and the study of buried solid/liquid (and solid/solid) interfaces. Fadley began with the all-important question of what’s happening at the interface, which he says drives a lot of his group’s research. Fadley uses the ambient pressure photoemission capabilities of the ALS to examine molecular-level structures, tuning to special resonant conditions to improve depth selectivity.

UC Berkeley’s Ting Xu spoke about deciphering hierarchical assemblies in supramolecular nanocomposites. Her research is focused on metamaterials, with a top-down engineering approach. Engineering supramolecular nanocomposites gives rise to materials with tailored mechanical, electrical, and optical properties for energy harvesting, storage, microelectronics, memory storage, sub-10-nm lithography, and light management.

ALS staff updates included User Services Group Leader Sue Bailey, who gave an overview of the new publication reporting system and the updated ALS experiment safety process. David Robin, head of the ALS Accelerator and Fusion Research Division (AFRD), reviewed accelerator, instrumentation, and controls upgrades.

The afternoon concluded with the ever-popular ALS Student Poster Slam, which gives recognition to significant student research conducted at the ALS. Students presented their posters on a wide variety of topics, with first prize going to Gregory Su, from UC Santa Barbara, for his poster "Phase Separated Polymer Blends for Organic Memory." Su gave a talk about his research the following morning, which focuses on using polymers and polymer blends for organic memory.

Tuesday morning began with a talk from Sherry Chen, from the Hong Kong University of Science and Technology, about studying reversible phase transformations by synchrotron x-ray Laue microdiffraction. Chen uses Beamline 12.3.2 to study unique microstructures, with the critical issue being functional degradation. The applications for research about these microstructures include medical devices and microelectronics devices.

This year’s Shirley Award winner, Beamline 8 staff scientist Wanli Yang, spoke about his research using soft x-ray spectrocscopy to study alkaline-based battery materials. The effort to improve batteries to meet growing energy needs requires a better understanding of their characteristics. “Battery research has a different focus depending on end use,” says Yang. “So we need different parameters of imaging.” Soft x-rays detect the key electron states that define the electronic properties of batteries, says Yang, and yet his research is still in the early stage of discovering how it can benefit the battery industry.

The Molecular Foundry’s David Prendergast, a computational physicist who often works with ALS users who are doing collaborative research at the two user facilities, spoke about understanding working interfaces at the nanoscale. “In-situ techniques are really useful to provide a unique insight on material system functionality,” says Prendergast. “But difficult theoretical problems remain.”


Alexander Laskin, from Pacific Northwest National Lab (PNNL), gave a talk about the discovery of unique atmospheric solid particles through chemical imaging. Using synchrotron techniques, researchers can assess particle types in the atmosphere and determine how they are formed and how they change. Laskin’s work also focuses on monitoring atmospheric aging and the atmospheric chemistry of aerosols.

Ilya Belopolski, a Princeton University physics graduate student in Zahid Hasan’s group, gave the final talk of the day, about the discovery of Weyl fermion and topological Fermi arc quasiparticles in condensed matter systems.

The second day of the 2015 User Meeting concluded with the annual awards dinner.

The Klaus Halbach Award for Innovative Instrumentation at the ALS was awarded to Hans Bechtel, Michael Martin, and Markus Raschke for the development of Synchrotron Infrared Nano Spectroscopy (SINS). The Tim Renner User Services Award was awarded to David Malone for his efforts to ensure users’ experiments run safely. The two were joined by Shirley Award winner Yang and Student Award winner Su.

Photo Story on Exposure

 
Reporting Publications Just Got Easier! Print

 

by Sue Bailey, User Services Group Leader

The ALS is starting to use the LBNL publication reporting system to capture most publications from ALS users. We invite you to test the system and This e-mail address is being protected from spambots. You need JavaScript enabled to view it . The significant advantages of the changes are:

  • Report journal articles by copying in the DOI or PubMed number. The system will then automatically download all publication details. No more typing in every separate field!
  • Publications are entered into both the LBNL and ALS databases removing the need for double entry for LBNL staff.
  • Publications are automatically transferred to the ALS database in real time.

 

To try out the new system:

  1. Click here.
  2. Look at the menu on the right-hand side.
  3. ALS users only: click on "Advanced Light Source User (not LBNL staff)"
  4. LBNL staff: click on "To Submit an LBNL Publication, Log In with your Berkeley Lab Identity"
  5. For publications without a DOI, select the option to "Manually type the citation," then select one of the following publication types:
  • Thesis
  • Patent
  • Book
  • Conference

Note: It appears that very occasionally a DOI may be rejected as invalid. We think this may be due to special characters carried across when "cut and paste" is used. If you receive an error, try re-typing the special character in the DOI.

So far approximately 100 publications have been reported through the new system. Thank you for your reporting all the products of your work at ALS. We look forward to receiving your feedback.

 
SIBYLS Beamline Builds on Nobel Research Print

 

The Nobel Prizes in scientific fields are awarded for discoveries or inventions that have “conferred the greatest benefit on mankind.” But often the full impact of a discovery takes decades to realize, during which the research is developed further and adopted by other scientists. Such was the case for the work of biochemist Paul Modrich, one of three recipients of the 2015 Nobel Prize in Chemistry “for mechanistic studies of DNA repair.” Berkeley Lab’s Advanced Light Source (ALS) was a core resource Modrich used to build on his earlier work.

DNA repair machinery impacts both why cancer occurs and how it is treated—the primary focus of LBNL's SBDR funding.

This year’s Nobel Prize has origins in the famous Nobel award from 53 years ago for solving the double-helix structure of DNA, which provides two complementary copies of genetic code and is essential to cell replication. However, James Watson and Francis Crick missed an important implication of their discovery. “They assumed DNA must be incredibly stable to maintain genome fidelity during replication,” says John Tainer, Berkeley Lab senior scientist and Professor of Molecular and Cellular Oncology at MD Anderson Cancer Center. “The trick is that you don’t maintain it. DNA is damaged constantly, but having two copies means if one strand becomes damaged, the complementary strand can be used as a template for repair.”

Understanding the mechanisms of that repair process has occupied the careers of many scientists since, including this year’s three Nobel laureates. Modrich’s contribution was in an area known as “mismatch repair,” which is coupled to replication. As cells divide, they frequently make mistakes or misspellings in the genetic code, incorrectly matching the base pairs of DNA’s two strands. Mismatch repair is the complex process that our bodies use to correct these misspellings. Learning how mismatch repair works—and how it can go wrong—is the key to stopping some types of cancer.

One effort seeking to better understand the mechanisms of mismatch repair has roots at Berkeley Lab and the ALS in particular. The Structural Cell Biology of DNA Repair Machines program (SBDR) involves more than 20 collaborators, including Modrich, from leading universities, national labs, and research institutes across the country. The list of collaborators reads like a who’s who of structural biology, biochemistry, and genetics—National Academy of Sciences members, fellows of every major professional society in the field, and now, a Nobel laureate. The program is funded by the National Cancer Institute of the National Institutes of Health and has been running for nearly 15 years, having been renewed twice.

Greg Hura, ALS beamline scientist, at work at SIBYLS.

Instead of duplicating work or creating competition among researchers, Tainer, the project leader, says the motivation behind the program was “to take the top researchers in DNA repair and link them together." The group's expertise, along with the technological capabilities available at Berkeley Lab, meant the program could tackle the grand challenge for cancer biology of achieving sufficiently detailed knowledge of DNA repair mechanisms to develop advanced cancer treatments with fewer adverse side effects. The knowledge Tainer’s team brought was in structural biology and mechanics, a new and crucial dimension for Modrich’s work.

Greg Hura, a beamline scientist at the ALS and member of the Molecular Biophysics and Integrated Bioimaging division at Berkeley Lab who has been with the project since its inception, describes Modrich’s earlier work on mismatch repair as a bit of trial and error. "He had some DNA synthesized with a mistake. Then he started adding proteins on top of it and assaying to see what was required for a fix. Eventually, he minimized the mixture to ten proteins essential to mismatch repair." Modrich then knew the what, but not the how. “What are the roles of these guys? Who comes on first? Who identifies the mismatch? Why are there ten?” are the questions Tainer and Hura devote their time to answering.

An essential tool for answering those questions is ALS Beamline 12.3.1 (Structurally Integrated Biology for Life Sciences, or SIBYLS), which was built specifically for SBDR. SIBYLS is unique in the world, incorporating both small-angle x-ray scattering (SAXS) and crystallography capabilities at the same endstation. Tainer likens the information SIBYLS provides about biological structure to different contexts for looking at animals.

Crystallized structures, he says, are like the animals you would find in a natural history museum—frozen in a fixed position. Crystallography allows you to look in great detail at that frozen snapshot. X-ray scattering, on the other hand, is like looking at animals in the zoo. It allows examination of structures and their movement in an environment that is like their natural habitat. SIBYLS combines the two types of information to look at the ensemble of structural states under conditions that resemble those in cells.

According to Tainer, the collaboration and access to SIBYLS had a strong impact on Modrich’s research, resulting in more than 20 published papers. “He really got directly involved in the structural work with a paper on the x-ray scattering and some papers on crystallography. I think it changed his thinking about these systems.”

Complex protein interactions make up the machinery of DNA repair. Modrich's work at SIBYLS provided a structural basis for understanding the impact of each protein (Exo1, MSH2/6, MLH1, PMS2, RFC, PCNA, and pol δ) he discovered as part of the repair cycle.

SIBYLS’s impact has reached far beyond Modrich and SBDR. Through additional funding from the U.S. Department of Energy and other sources, SIBYLS has studied hundreds of DNA repair processes. “Fifteen years ago, SAXS was a niche technique that only two or three labs were using,” says Hura. “Crystallography was really well developed, so it was kind of a risk to put SAXS on a crystallography beamline. This group really helped push SAXS to the point that we now have hundreds of labs using the technique.”

Both Tainer and Hura are quick to credit others as critical to SIBYLS’s existence and success. “[Modrich] really helped build this beamline,” explains Hura. “He’s central to why this collaboration got funded, and the work he was interested in doing helped drive our research.” Tainer says SIBYLS is “the design of a lot of very smart people at LBL. People like [ALS Deputy for Experimental Systems] Howard Padmore and all the machine physics guys and the engineers are the magic that meant we could do something special to address the biology of DNA repair. It’s a unique strength of LBL that this facility could be built and that we could involve such top-notch people to run a program for 15 years."

Tainer and Hura hope SBDR will continue to be funded to probe the remaining mysteries of DNA repair, with the aim of unlocking more effective cancer treatments. “There are a lot of unanswered questions,” says Hura. “There’s still huge debate about how the broken spots are identified. We have pieces of the information, but we’re continuing to come up with rationally designed strategies to better understand and control the process.”

 
Wolfgang Eberhardt on Light Sources: Getting the Balance Right Print

 

Wolfgang Eberhardt at the Advanced Light Source, September 2015. Click the image to watch the video of his talk, "Diffraction Limited Storage Rings and Free Electron Lasers—Why Do We Need Both?"

As a graduate student in the 1970s, Wolfgang Eberhardt conducted his first experiment at the old DESY synchrotron in Hamburg, Germany. A so-called "parasitic" operation on a high-energy physics ring, it had tremendous difficulties, including highly erratic, fluctuating pulses.

"Nowadays," he says, "nobody would even consider doing experiments under those conditions." Nevertheless, photon science at the time was new, so "whatever you looked at, whatever you studied, it was pretty much for sure that nobody had seen that before. It was very exciting."

Eberhardt, a Professor of Physics at the Technical University of Berlin and a Leading Scientist at Helmholtz Zentrum Berlin (HZB) and the Center for Free-Electron Laser Science (CFEL) at DESY, is currently wrapping up an extended visit to the ALS, working on furthering our basic understanding of organic solar-cell materials.

In addition to serving as Scientific Director of BESSY (the synchrotron in Berlin) from 2001–2008, Eberhardt has published over 300 refereed papers on topics ranging from the development of angle-resolved photoemission, to femtosecond magnetization dynamics, to scattering and holography with coherent synchrotron radiation. He is an internationally respected and sought-after expert in the generation and application of synchrotron radiation and has served on a long list of advisory boards, councils, and committtees across Europe, the US, and Asia. In 2008, he co-chaired with Franz Himpsel a DOE BESAC workshop on "Next-Generation Photon Sources for Grand Challenges in Science and Energy."

Now, with a diffraction-limited ALS upgrade (ALS-U) on the horizon, Eberhardt agreed to give a special ALS seminar this month on "Diffraction Limited Storage Rings and Free Electron Lasers—Why Do We Need Both?" He pointed out that synchrotron science at storage rings has been fantastically successful, but attention has recently turned somewhat to the construction of free-electron laser facilities. "There's lots of science, very exciting science out there," Eberhardt said in an interview following the seminar, "and the science cannot be mapped uniquely onto one specific facility." While this message came through in the 2008 BESAC workshop report, he said, "the distinction—what can you do better with what facility—that is still a learning process."

Eberhardt summarized his current understanding of that distinction: "If you want to look at processes, if you want to look at function of materials, you need to do movies, consecutive interrogations of the same object and see how it evolves under certain conditions. How a reaction progresses, for example. So you can't take one snapshot and know it all—what happens. This is clearly the realm of the new diffraction-limited storage rings."

On the other hand, "if you want to have snapshots at the best determined time to investigate and freeze a state of a system, then that's the free-electron laser, because that allows you to get really the best time resolution. But it only allows you to get a single picture—or maybe a double picture—it doesn't allow you to really do a full movie," before the sample is destroyed or changed by the x-ray pulses.

Ultimately, achieving the right balance between ring sources and linac sources is a many-dimensional problem that can't be captured in a simple two-dimensional matrix of science areas vs. photon attributes. You also have to take into account timing, budgets, risks, and changes in technology over time.

"When the ALS was built," says Eberhardt, "it was the most modern, most fantastic machine that existed in the world. All the scientists came from everywhere to do experiments. It was really fantastic." Now, more modern, diffraction-limited x-ray facilities are being built, such as MAX IV in Sweden. While there are always certain risks involved whenever you try something totally new, with respect to the MAX IV design, "right now it looks like these risks can be handled and the challenges can be met."

Eberhardt is quick to note that the ALS has not stood still, but has been continuously upgraded. "The machine has improved as much as it can be in the normal program, the instrumentation is continually being upgraded," he says. "But right now, it's due for a major upgrade, this refurbishment, simply because accelerator design has advanced. And that's what the ALS-U is about."

Eberhardt cautions against simple calculations about cost per experiment. "What is the Higgs boson worth?" he asks. "Certainly in physics, chemistry, there are many different Higgs bosons around." When pressed on the question, Eberhardt cited the example of high-temperature superconductivity. "It's a very strange mechanism; to really pin that down and say why are all these materials behaving that way, that would be very exciting." On the question of whether we really need both diffraction-limited storage rings and free-electron laser facilities or can we manage with just one or the other, Eberhardt is clear: "My firm position on that one is you really need both, because they are really complementary."

 
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