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SSRL Headlines Vol. 5, No. 6  December, 2004


Contents of this Issue:

  1. End of Year Message from the SSRL Director
  2. Science Highlight — Crystal Structure of Botox® Protease with Its Substrate Reveals a Large Enzyme-Substrate Interface Which Could Help Inhibitor Design
  3. Science Highlight — New Imaging Technique Opens Door to the Nanoscale World
  4. FY2005 Budget
  5. Fall Meeting of the Scientific Policy Committee
  6. General Announcements
  7. Synchrotrons in the News

1.   End of Year Message from the SSRL Director
      (contact: Keith Hodgson,

Calendar year 2004 has been yet another extraordinary year for SSRL. We completed the commissioning of SPEAR3 and had our first users back on-line in less than a year after we began the shutdown for the major installation. Following the beginning of the user run in mid-March, SPEAR3 was operated for users until July 31. Over this period, a remarkable 97% of scheduled beam was delivered. The beam line upgrade program and construction of new beam lines continued to make significant progress over the year and during the summer shutdown. SPPS had several very productive runs and significant new results on timing between laser and x-ray beams were made. LCLS continued to increase in level of activity (detailed engineering and design) and has just undergone a major transition with essentially full funding in the FY2005 budget for beginning to acquire real components of what will be the world's first x-ray FEL when it becomes operational in 2009. The LCLS science program is also accelerating with the selection and formation of the initial scientific teams. A new Center for Ultrafast Science at SSRL/Stanford has also been funded this year and will provide the opportunity to build up outstanding faculty-based research efforts, which will take advantage of the unique capabilities of LCLS. All of this would not have been possible without the dedication and hard work of a very talented staff and faculty and the strong support of our funding agencies - DOE-BES for core operations, LCLS and materials/chemical sciences research and DOE-BER and NIH for the structural biology program. The serious electrical accident at SLAC which occurred this fall gave rise to a significant interruption of our SPEAR3 user program. I want to assure you that we have strongly engaged, together with our colleagues in the rest of SLAC, in a careful re-evaluation of hazards and processes related to safe work. As we emerge from our accelerator shutdown in early 2005, we look forward to all of our users returning to an environment that is even safer than before. The coming year promises to be yet again a great one for photon science and we thank you all for your support. With very best wishes to everyone - our staff, our users, those who serve on our committees and the many officials in our sponsoring agencies - for the holiday season and a most productive new year! Keith

2.  Science Highlight — Crystal Structure of Botox® Protease with Its Substrate Reveals a Large Enzyme-Substrate Interface Which Could Help Inhibitor Design
      (contact: Axel T. Brunger,

The Botox face lifts and botulism disease are both caused by a neurotoxin from the bacterium Clostridium botulinum. The toxin, often described as the most lethal substance known, is a member of the clostridal neurotoxins (CNTs) group, which block muscle contractions. When injected into someone's face, the effect is a lessening of wrinkles. When ingested, the toxin paralyzes muscles, including those of the internal organs, causing sickness and death. The toxin is also used in medicine for conditions such as uncontrolled blinking, lazy eye, and involuntary muscle contractions.

Nerve cells cause muscles to move by delivering the neurotransmitter acetylcholine into muscle cells. CNTs paralyze muscles by blocking acetylcholine delivery. CNTs enter nerve cells then find and cut SNARE proteins, the machinery responsible for acetylcholine delivery. The inactivation of nerve cells lasts for three to six months.

Breidenbach and Brunger of Stanford have used SSRL and SPEAR3 to solve the first crystal structure of a CNT bound to a SNARE. They found extensive contact between the toxin and its target - much more than the typical lock-and-key paradigm. In kinetic experiments based on the crystal structure, the authors found that the toxin wraps the target SNARE protein around itself. This ensures both target specificity and proper positioning for cutting the SNARE. Knowing the structure of the CNT-SNARE interaction furthers understanding of the toxin's mechanism and may lead to drugs that can treat CNT poisoning.

To learn more about this research published in the December 16, 2004 edition of Nature, see: or

3.  Science Highlight — New Imaging Technique Opens Door to the Nanoscale World
      (contact: J. Lüning,

Researchers at the Stanford Synchrotron Radiation Laboratory (SSRL) and the German laboratory BESSY have crafted a versatile and stunningly effective technique to take x-ray images of tiny variations and lightning-quick changes in materials a thousand times smaller than the thickness of a strand of hair. Their work merits the cover of the December 16 issue of Nature. Researchers Jan Lüning of SSRL, Stefan Eisebitt of BESSY and their colleagues demonstrated the first direct imaging technique - lensless x-ray holography - that will work at the world's first x-ray free electron laser, the Linac Coherent Light Source (LCLS), slated to open at SLAC in 2009. Lensless imaging opens the door for "single shot" pictures at LCLS using just one pulse of x-ray light to capture a clear picture of ultra-fast action occurring on ultra-small length scale.

In the demonstration experiment at BESSY the team recorded an image revealing the randomly organized "north" and "south" magnetic regions of a cobalt-platinum film to a spatial resolution of 50 nanometers (50 billionths of a meter). Because the technique uses no lenses, lensless imaging has the potential to take direct images with 10 times better spatial resolution than achievable with current x-ray lenses. The technique works by shining a coherent beam of x-ray light through two adjacent holes: one containing the sample to be studied, the other a tiny "reference" hole. The scattered light from both holes overlays to form a single, holographic diffraction pattern. Holography not only maps the intensities of the light, as do normal diffraction patterns, it also encodes information about the phases of the light that is otherwise intrinsically lost. The information is decoded by applying a powerful mathematical procedure known as Fourier transformation, yielding a complete image of the sample.

To learn more about this research, see: or

4.   FY2005 Budget
      (contact: Keith Hodgson,

In November and early December, Congress completed work on the FY2005 appropriations bills. The FY2005 Consolidated Appropriations Bill (or Omnibus) provided funding to most of the Federal agencies supporting R&D, including the DOE Office of Science. While overall spending in FY2005 was held to levels similar to those in FY2004, there were some basic science areas that saw new opportunities and modest growth. The DOE Office of Basic Energy Sciences was among these where the funding level enabled construction projects (the nanoscience centers, the SNS and the LCLS - see item 1., above) to go forward. There are also reasonable operations budgets for the four DOE synchrotron facilities and opportunities for some new initiatives in upgrades and beam line developments. Those interested are encouraged to visit the AAAS web site where there is an excellent analysis and perspective on Federal R&D:

5.   Fall Meeting of the Scientific Policy Committee
      (contact: Keith Hodgson,

The fall meeting of the SLAC Scientific Policy Committee (SPC) took place on December 3-4. The SPC, which reports to Stanford President John Hennessy, is the highest level advisory board for science programs at SLAC. We are very pleased to have the collective expertise of the SPC serve in this capacity and give thanks to the 7 members, including Chair James Brau (University of Oregon) who will rotate off of the committee at the end of this month. Jim Siegrist (LBNL) has been named the new chair of the SPC. We are especially grateful for the contributions of departing member Jens Als-Nielsen (University of Copenhagen) who has represented the synchrotron radiation area for the past 8 years without missing a single meeting.

Overview presentations were given on the high energy physics and synchrotron programs recognizing the highly successful PEP and SPEAR3 experimental runs in FY2004. John Galayda gave a presentation on the progress of LCLS. Additionally, the SPC was given an update on the recent NIH NCRR and DOE BER peer review of SSRL's structural biology program which from all indications went well. The report should be available to the PI soon. The high energy physics budget was also discussed, but the electrical accident and its impact on the SLAC scientific program and supporting activities was the primary focus of discussion.

6.   General Announcements

Staff and users interested in joining the American Physical Society Division of Physics of Beams (DPB) can do so via the web at: (An APS WEB username and password are needed to access this, and these can be set up using the same link. Cost is $7 annually in addition to APS membership). The DPB is for those who design, operate and improve the accelerators on which many user scientific programs are based; DPB provides services to the accelerator community including the PRST-AB Journal, biennial Particle Accelerator Conference, APS Prizes and Fellowships, and representation of the accelerator field to the broader science community. For more information, contact Nan Phinney (Chair, Division of Physics of Beams, APS) at

7.   Synchrotrons in the News

An article by Mike Perricone titled "Sesame: Can a Recycled Synchrotron Become an Oasis of Peace in the Middle East?" appears in the latest edition of Symmetry, a joint Fermilab/SLAC publication. For more information on Sesame and this article see:


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: 17 DEC 2004
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