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SSRL Headlines Vol. 6, No. 9  March, 2006


Contents of this Issue:

  1. Science Highlight — Two Negatives Make a Positive for Gene Therapy
  2. Science Highlight — Complete Reaction Cycle of a Cocaine Antibody
  3. Science Highlight — Structure of a SARS Protein
  4. Teamwork Restores Beam in SPEAR3
  5. SPPS Experiment Concludes in March
  6. Progress on New Beam Line for Advanced Micro-crystal Analysis
  7. Using X-ray Fluorescence to Reveal Archimedes' Buried Text
  8. Department of Energy Officials Visit SLAC
  9. SSRL Users' Organization Executive Committee to Meet April 17
  10. Upcoming Meetings
  11. User Administration Update
  12. Photon Science Job Opportunities

1.  Science Highlight — Two Negatives Make a Positive for Gene Therapy
      (contact: G.C.L. Wong,

Gene therapy can potentially cure many hereditary and acquired diseases, such as cancer, hemophilia and cystic fibrosis, by delivering a healthy copy of a gene to the cells that need it. Researchers have been working on ways to deliver genes safely and effectively to the right locations. One promising approach is to use negatively charged lipids that reside in cell membranes of mammals. The idea is to pack a gene, made of DNA, into a lipid pocket, which then fuses with a cell membrane and empties the gene into the cell. The advantage of these anionic lipids (AL) is they do not evoke an immune response. The disadvantage is they do not attach well to DNA because both are negatively charged.

Researchers from the University of Illinois at Urbana-Champaign and the National Institutes of Health used x-ray techniques at BL4-2 at Stanford Synchrotron Radiation Laboratory and at the Advanced Photon Source at Argonne to investigate how to stick AL and DNA together. They made AL-DNA complexes using different kinds of positively charged ions to act as the glue. DNA could be packed into or expelled from a lipid pocket depending on the concentrations of the ions being used and the density of negative charge on the lipid. The researchers found that these different AL-DNA structures can be understood in terms of a simple theoretical model, which can serve as a recipe book for the design of the next generation of gene delivery agents.

To learn more about this research see the full technical highlight at:

 AL-DNA figure
Schematic pictures of (A) Condensed DNA-ion-membrane lamellar structure with alternating layers of DNA and anionic membranes 'glued' together by divalent cations; (B) Condensed ion-membrane lamellar structure in which charged membranes stacks are held together by divalent cations; and (C) 2-D inverted hexagonal structure in which hexagonal arrays of divalent cations coated DNA strands wrapped in the anionic membrane monolayer tubes.

2.  Science Highlight — Complete Reaction Cycle of a Cocaine Antibody
       (contact: I.A. Wilson,

 7A1 figure
Crystal structure of the 7A1 Fab' cocaine complex with the secondary structure of the antibody light (L) and heavy (H) chains colored in cyan. Substrate cocaine is also shown in spheres with yellow carbons, blue nitrogen, and red oxygens in the active site.
Cocaine abuse remains a major public health problem despite ongoing research aimed at developing therapies to counter its harmful effects. Immunopharmacotherapy is one proposed therapy which would block cocaine in the blood stream before it reaches the central nervous system. Cocaine-binding antibodies seem likely candidates for soaking up drugs in the blood stream, but their only binding abilities are not sufficient to withstand high concentrations of the drug. What is needed is a monoclonal antibody with high binding characteristics and sufficient catalytic ability to metabolize cocaine. The Wilson and Janda groups at The Scripps Research Institute are hopeful that they have found these properties in 7A1, a catalytic monoclonal antibody that has the ability to regenerate after each new dose of the drug. Aided by x-ray crystallography, their research has revealed for the first time the complete reaction cycle of a 7A1 Fab' antigen binding fragment. The high resolution crystal structures revealed the conformational changes that occur during the antibody's complete catalytic cycle and provided a molecular basis for catalysis. Understanding these significant structural changes of the antibody is a promising step towards the development of a treatment for cocaine addiction.

To learn more about this research see the full technical highlight at:

3.  Science Highlight — Structure of a SARS Protein
       (contact: P. Kuhn,

nsp3 figure
Severe acute respiratory syndrome (SARS) emerged as the first severe and readily transmissible new disease of the 21st century. The debilitating pneumonia-like disease is caused by coronavirus, which caused 916 deaths out of about 8,400 reported cases. Scientists from The Scripps Research Institute in California have embarked on an ambitious program to characterize the structure and function of all the proteins built or used by SARS. Taking advantage of advances in robotics and automation at Stanford Synchrotron Radiation Laboratory as well as other new tools, the scientists ultimately hope to rapidly characterize the complete protein sets of emerging disease organisms and then provide structure information to design inhibitors to stop the organisms.

In a recent paper, the group reported the structure of a part of one SARS protein, one of the first resulting from the Scripps project, and with the data measured on SSRL's BL11-1. The high resolution structure is providing insights into mechanisms the virus uses to replicate itself.

To learn more about this research see the full technical highlight at:

4.   Teamwork Restores Beam in SPEAR3
      (contacts: R. Hettel,; E. Guerra,

Thanks to SLAC teamwork, a problem with a high voltage power supply for the SPEAR3 booster RF system earlier which occurred on Wednesday, March 8, was rapidly addressed. Although the exact nature and severity of the problem were not readily apparent at first, the SSRL Electrical Systems and Mechanical Services groups planned for various scenarios to make anticipated repairs. Once it was determined that the power supply needed to be replaced, activities were closely coordinated with the SLAC rigging crew (CEF) to extract the supply from its storage space in PEP region 12 and with the SSRL facilities group who quickly arranged for a contractor to take down a wall in building 140 in order to access the failed power supply. Removal work was temporarily halted when an unidentified odorous gas was detected upon opening an oil inspection access port for the supply. The Industrial Safety group (ES&H) analyzed the gas and found it to be flammable, so work recommenced only after the gas had safely dissipated. The spare supply was installed by Wednesday evening and was left overnight to allow bubbles in the newly added insulating oil to escape. Electrical testing commenced on Thursday morning, but only after a special effort was made to liberate the variable voltage transformer (VVT) test cart from behind the jammed roll-up door to the PEP region 2 storage area. With SSRL users anxiously waiting for beam, those responsible for the VVT, building and labor pool, including CEP, PEP II/Accelerator Systems and CEF, quickly agreed that the VVT needed to be extracted as soon as possible, even if it meant cutting a hole in the rolling door. As it turned out, the jammed door could be opened just enough with the aid of a forklift to liberate the VVT test cart, and the power supply testing was carried out successfully. After one last hurdle involving the update of a circuit breaker arc flash hazard label, which was quickly accommodated, the booster RF system was turned on and SPEAR3 beam was re-delivered to users on Thursday afternoon, March 9. SSRL is indebted to all who participated in the replacement of the RF power supply and is grateful for the close cooperation of the SLAC groups that facilitated the repair.

SPPS logo 5.   SPPS Experiment Concludes in March
      (contacts: J. Hastings,; A. Lindenberg,
The remarkable experiments conducted with the Sub-Picosecond Pulse Source (SPPS) in the Final Focus Test Beam (FFTB) at SLAC concluded in March because the FFTB building is being dismantled to make way for construction of its successor, the Linac Coherent Light Source. By generating the world's shortest bunches of electrons and turning them into ultrafast pulses of x-ray light, SPPS observed a previously unseen world -- where atoms and materials move too quickly for synchrotron x-ray beams and are too small for ultrafast visible light lasers. The SPPS had a series of very successful runs during the past three years, specifically they have: measured the earliest atomic motions that occur when a solid melts; learned how to put data in order chronologically by successfully time-stamping the arrivals of the x-ray pulse and the laser pulse used to start chemical reactions; explored how to use light to control and shape the potential-energy surface that determines where atoms go and the forces they feel; and observed atoms vibrating on 100-femtosecond time scales. The highly productive collaboration included about 50 researchers from 10 institutions, a significant increase over traditional synchrotron x-ray collaborations. For more information on SPPS experiments see:

6.  Progress on New Beam Line for Advanced Micro-crystal Analysis
      (contact: D. Harrington,

Great strides have been made in the design, procurement and fabrication of Beam Line 12-2, the new macromolecular crystallography beam line at SSRL. The $12.35 million project is funded by a generous contribution from the Gordon and Betty Moore Foundation through the California Institute of Technology. The beam line is designed to allow the analysis of very small macromolecular crystals by providing a high brightness x-ray source, superior focusing optics and advanced crystal positioning and visualization hardware. To achieve high brightness, SSRL's first in-vacuum undulator will be installed in the SPEAR3 ring and will take full advantage of the upgraded storage ring capabilities. A unique modification of the SPEAR3 lattice is also being implemented to create two independent insertion device positions in a single long straight section in the ring. Most of the mechanical design work for the beam line is complete and much of the hardware is being fabricated and assembled at this time. The conventional construction project to provide a shield wall alcove is complete, while further facility modifications needed to install the beam line are planned for early spring. Experimental equipment to allow manipulation of very small samples has been specified which will allow much of the current macromolecular crystallography infrastructure to be used in the new experimental end station. This will create a user-friendly facility capable of advanced micro-crystal analyses as well as standard macromolecular crystallography experiments. The beam line will be installed this summer and is on schedule for commissioning to begin in the fall.

7.   Using X-ray Fluorescence to Reveal Archimedes' Buried Text
       (contact: U. Bergmann,

archimedes text
Archimedes' text and a fragment of a diagram depicting a hand.
The "Archimedes" experiment was online again at SSRL earlier this month. Following upon the success of their first attempt last spring in using x-ray fluorescence to detect traces of iron in the ink from a 10th century copy of Archimedes' treatises (buried under medieval prayer book writings and 20th century painting forgeries), a preservation team from The Walters Art Museum in Baltimore brought seven additional manuscript pages to BL6-2 for more experiments. For this data collection SSRL staff scientist Uwe Bergmann and the team from Walters measured fluorescence from zinc and barium in an effort to isolate the paint pigment from the ink. For more information see:

Garman, Schwartz & Hodgson
(from left) Under Secretary David Garman with Doug Schwartz and Keith Hodgson.
8.   DOE Officials Visit SLAC

U.S. Department of Energy Under Secretary David Garman visited SLAC on March 22. His visit included a meeting with the DOE Site Office, discussions on the ILC and the LCLS project, and a tour of BaBar, GLAST and SSRL. Specific tour stops at SSRL included BLs 5, 6-2, 9-1 and 11-2 where users and staff briefly discussed the objectives of their synchrotron-based research at SSRL.

Dr. Julie Carruthers, a science advisor in the DOE Office of Science, visited SLAC and SSRL later that afternoon.

9.  SSRL Users' Organization Executive Committee to Meet April 17
      (contacts: J. Andrews,; C. Kim,; A. Lindenberg,

The SSRL Users' Organization Executive Committee (SSRLUOEC) meets throughout the year to discuss issues of interest to the user community. Users are invited to participate in the next meeting, which will be held on April 17. Topics for discussion include recent user advocacy activities as well as plans for the 33rd Annual SSRL Users' Meeting (SSRL33), scheduled for October 12-13. Aaron Lindenberg (SSRL) and Chris Kim (Chapman University), co-chairs for SSRL33, solicit your suggestions for speakers or workshop topics--these could cover areas of current activity at SSRL as well as exciting fields on the horizon. Workshops on areas of mutual interest could also be conducted jointly with the Advanced Light Source in Berkeley. Please contact anyone on the SSRLUOEC with your suggestions or questions - we welcome your input!

10.  Upcoming Meetings

Workshop on Synchrotron X-ray Scattering Techniques in Materials and Environmental Sciences: Theory and Application, May 16-17, 2006, SSRL/SLAC, Menlo Park, CA: This workshop will provide a guide to planning and conducting scattering measurements at several SSRL beam lines. Note that registration for the practical session on the beam lines for the second day is full, but there is still space available for the classroom discussion. Register at:

Berkeley-Stanford Summer School on Synchrotron Radiation and Its Applications, June 26-30, 2006, Berkeley, CA: The 2006 Summer School Program will be taking place this year on the UC Berkeley campus. Detailed program and registration information on the 2006 Summer School will be forthcoming at:

XAFS13, July 9-14, 2006, Stanford, CA: The 13th International Conference on X-ray Absorption Fine Structure (XAFS13) will be held at Stanford on July 9-14. Many techniques and the theory focusing on XAFS-related phenomena will be covered, as will applications to a wide range of scientific areas. Register before May 1 for the early registration discount.

11.  User Administration Update
      (contacts: C. Knotts,; L. Dunn,

The next deadline for new Macromolecular Crystallography proposals is April 1; new X-ray and VUV proposals are due by May 1. For more information on the proposal submittal, review and scheduling process, visit:

12.   Photon Science Job Opportunities

A number of positions are currently available at LCLS, LUSI and SSRL. Please refer to the Photon Science Job Openings page at for more information about these job opportunities.


SSRL Headlines is published electronically monthly to inform SSRL users, sponsors and other interested people about happenings at SSRL. SSRL is a national synchrotron user facility operated by Stanford University for the U.S. Department of Energy Office of Basic Energy Sciences. Additional support for the structural biology program is provided by the DOE Office of Biological and Environmental Research, the NIH National Center for Research Resources and the NIH Institute for General Medical Sciences. Additional information about SSRL and its operation and schedules is available from the SSRL WWW site.


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Last Updated: 27 MAR 2006
Content Owner: L. Dunn
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