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SSRL Headlines Vol. 7, No. 9  March, 2007

Contents of this Issue:

Science Highlight — Taming a Potent Toxin Science Highlight — Ancient Warriors and the Origin of Chinese Purple Stanford-Caltech Collaboration Creates New X-ray "Molecular Observatory" Rapid Access Beam Time for SMB XAS BL7-3 SSRL School on Hard X-ray Scattering: Techniques in Materials and Environmental Sciences 2007 Ultrafast Summer School - June 18-22 SMB XAS Short Course Wrap-Up SSRL Users, Affiliates and Faculty Honored Upcoming Beam Time Proposal Deadlines Photon Science Job Opportunities

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1.  Science Highlight — Taming a Potent Toxin
       (contacts: Q. Chai, qingchai@scripps.edu and R. Stevens, stevens@scripps.edu, TSRI;
          R. Jin, rsjin@slac.stanford.edu and A. Brunger, axel.brunger@stanford.edu, Stanford University)

Botulinum neurotoxin is produced by the bacteria Clostridium botulinum and is the most potent toxin known, inducing a potentially fatal paralysis known as "botulism." Botulism can occur in a number of ways, including infection through open wounds or in the intestinal tract, or after consuming contaminated food in which toxin has been produced. In the USA, infant botulism is the most common manifestation of the disease-some speculate whether its prevalence is linked to sudden infant death syndrome. On the other hand, these neurotoxins have also become a powerful therapeutic tool for treating a variety of neurological, ophthalmic, and other disorders manifested by abnormal, excessive, or inappropriate muscle contractions.

In a recent series of x-ray crystallography studies conducted in part at SSRL, two research groups have determined the mechanism by which the botulinum neurotoxin binds to nerve receptors and causes infection, which could lead to new preventive and therapeutic treatments. The work is published in the December 13, 2006, issue of Nature.

Recently, researchers from a collaboration led by The Scripps Research Institute completed studies on the structures of botulinum toxin in complex with a neuronal cell surface receptor and botulinum toxin with two different neutralizing antibodies, each to a resolution of 2.6 Å. The group also performed biochemical, mutagenesis, and neurobiology experiments to complement the structural work. The interdisciplinary research projects provide insight into the atomic details on the intoxication process, and the means by which antibodies neutralize the effects. These structures open the possibility of developing improved broad-spectrum therapeutics, including antibodies, small molecule drugs and vaccines against the toxin.

In an adjoining study published in the same issue of Nature, Axel Brunger's group at Stanford University determined the first crystal structure of a botulinum neurotoxin in complex with its protein receptor to a resolution of 2.15 Å. The results could lead to development of preventive vaccines or inhibitors against these neurotoxins. Additionally, owing to the specific geometry of the binding mechanism, this study suggests that appropriately modified botulinum neurotoxins could also be used as drug delivery systems.

The three-dimensional structure of botulinum neurotoxin-one of the most deadly toxins in the world-is shown here binding to the cell surface receptor synaptotagmin and being internalized via synaptic vesicle recycling. [Stevens]		Botulinum neurotoxin hijacks synaptic vesicle recycling at neuromuscular junctions. The toxin first docks to the active zone (blue) by binding to two membrane-anchored receptors, synaptotagmin (red) and ganglioside (yellow). The toxin-receptor complexes are then internalized by endocytosis. [Brunger]

To learn more about this research see the Stevens and Brunger scientific highlights at:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/BoNT-stevens.html and
http://www-ssrl.slac.stanford.edu/research/highlights_archive/BoNT-brunger.html

2.  Science Highlight — Ancient Warriors and the Origin of Chinese Purple
      (contact: Z. Liu, zhiliu@stanford.edu)

	Samples of a pigment called Chinese purple were obtained from this kneeling archer, one of 8,000 terra cotta warriors discovered in 1974.

In 1974, while sinking irrigation wells in the Chinese province of Shaanxi, a group of farmers made an astonishing archeological discovery. Buried beneath their feet stood a contingent of 8,000 life-sized terra cotta warriors and their horses, facing east, ready for battle. The figures, later found to be more than 2,000 years old, were accompanied by weapons, real chariots, and objects of jade and bone. It was later determined that this army was built to protect the tomb of the first emperor of the Qin dynasty, Shi Huang Di.

Today many puzzles still surround these statues. One of the most intriguing of these mysteries is the origin of a synthetic purple pigment, often called "Chinese purple" or "Han purple," that their ancient creators used to adorn the soldiers and their accessories. Until the 19th century, most pigments were made from naturally occurring minerals or organic dyes. One well-known exception is "Egyptian blue," which is chemically very similar to the Chinese purple. Because the Egyptian and Chinese pigments are so chemically close in composition, some have proposed that the technology to create Chinese purple was in fact derived from the Egyptians. If that were so, Chinese purple would represent one of the earliest known cases of cross-cultural technology transfer, dating to a period before the Silk Road opened China to the west, even before the invention of paper or the compass.

To test this hypothesis, SSRL researchers Zhi Liu, Apurva Mehta and colleagues from Stanford University, the Advanced Light Source and China used a series of synchrotron-based x-ray techniques, in particular micro-x-ray diffraction and micro-x-ray fluorescence, to characterize the exact chemical make-up of the pigments in Chinese purple. Liu found that deep within the structure of Egyptian blue, calcium plays a key role in the pigment's molecular identity, whereas in Chinese purple, that same slot is filled by the element barium. Liu concluded that, based on this difference, and despite the two pigments' structural similarity, Chinese artisans invented Chinese purple independently of Egyptian influence.

"Stable purple is rare in nature," Liu said. "People already knew what the pigment was, but by making a chemical map and combining it with archeological evidence, we were able to solve the puzzle of where it came from."

Scholars believe that Chinese alchemists 2,200 years ago were most interested in synthesizing jade, a mineral regarded as sacred in Taoist culture. Liu's analysis found that, based on the combination of compounds used to make the pigment and the technologies available to Chinese artisans at the time, Chinese purple was most likely first developed by Taoist glassmakers attempting to create artificial jade.

To learn more about this research see the full scientific highlight at:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/chinesepurple.html

3.  Stanford-Caltech Collaboration Creates New X-ray "Molecular Observatory"
      (contact: K.O. Hodgson, hodgson@ssrl.slac.stanford.edu)

Gordon Moore, just after unveiling a plaque at the newly dedicated Molecular Observatory for Structural Molecular Biology at Beam Line 12. (Photo courtesy of Diana Rogers.)

Last Friday, a group of distinguished guests gathered at the Stanford Synchrotron Radiation Laboratory (SSRL) before a crowd of one hundred scientists and staff for the official dedication of the new Molecular Observatory for Structural Molecular Biology at Beam Line 12. Dignitaries included Stanford President John Hennessy, Caltech President Jean-Lou Chameau and Intel co-founder and philanthropist Gordon Moore.

"The new beam line being dedicated today will enable Caltech scientists and SSRL's users to address problems at the cutting edge of structural biology research," said Photon Science Director Keith Hodgson. "We are very grateful to the Gordon and Betty Moore Foundation for their visionary investment."

Just as astronomers use specialized observatories to study distant galaxies, chemists and molecular biologists need advanced tools for studying nano-scale structures-in some ways as inaccessible as the far reaches of the cosmos. Now, thanks to a collaboration among Stanford University, the California Institute of Technology and the Gordon and Betty Moore Foundation, researchers have a new tool for studying in great detail the molecules that make up living systems. The new molecular observatory will help unlock the secrets of organic molecules on the atomic level with an unprecedented degree of precision. See the full press release at: http://www.lightsources.org/cms/?pid=1002042

4.   Rapid Access Beam Time for SMB XAS BL7-3
      (contact: S. DeBeer George, serena@slac.stanford.edu)

Beginning in May, a new rapid access proposal mechanism for biological x-ray absorption spectroscopy (XAS) will be implemented on SSRL's BL7-3. A block of 6 shifts of beam time will be set aside each month for rapid access user runs. This time will allow new and current biological XAS users to perform feasibility tests. Allocation of time will be based on a one-page scientific proposal, which will be reviewed by the SMB subpanel of the PRP. Rapid access proposal should be submitted by the first of each month, and users will be notified ~2 weeks prior to their allocated beam time. New users scheduled for beam time under a rapid access proposal will be trained by SSRL staff. Staff will provide training on all aspects of the experimental setup (beam line optics, use of detectors, data collection software) and will also advise users on sample preparation and data analysis. This will help new users efficiently utilize their beam time, and prepare them for successful future experiments. The rapid access proposal process should also benefit existing biological XAS users, allowing a mechanism for testing new ideas outside existing proposals. A rapid access beam time proposal form will be posted through the SSRL website soon. For questions, please contact Serena DeBeer George (serena@slac.stanford.edu).

5.  SSRL School on Hard X-ray Scattering: Techniques in Materials and Environmental Sciences - May 15-17
      (contact: John Bargar, Bargar@slac.stanford.edu)

Overview: Modern synchrotron-based X-ray scattering (SR-XRS) techniques offer the ability to probe nano- and atomic-scale structures and order/disorder relationships that critically govern the properties of advanced technological and environmental materials. The high collimation, intensity, and tunability of SR allow the investigation of a wide range of materials, including thin films and interfaces, nanoparticles, amorphous materials, solutions, hydrated and disordered bacteriogenic minerals, soils, and highly crystalline materials.

Good planning and a working knowledge of beam lines, in addition to techniques, are keys to conducting successful SR-XRS measurements. This school will provide a practical users' guide to planning and conducting scattering measurements at SSRL beam lines. Important techniques, including surface and thin-film scattering, powder diffraction, in-situ x-ray scattering, and amorphous materials will be covered. In all cases, we will cover topics that are not commonly addressed in text books or class lectures, but are typically obtained only through on-the-experiment training. The first day of the school (May 15), will be a lecture day.

The school includes two days of hands-on training at SSRL hard x-ray scattering beam lines (May 16 and 17; registration limited to 20 participants). Costs will be $25 for graduate students and $50 for all others. Register at:
http://www-ssrl.slac.stanford.edu/conferences/workshops/scatter2007/reg.php

6.   2007 Ultrafast Summer School - June 18-22
       (Summer School Chairs: N. Berrah, Western Michigan University; P. Bucksbaum, Stanford University/SLAC)

	2007 Ultrafast Summer School Website

Stanford University's PULSE Center, located at the Stanford Linear Accelerator Center, is hosting the 2007 Ultrafast Summer School, June 18-22.

The ultrafast summer school will offer a five-day residential program to present comprehensive lectures and open forum for discussions about free electron lasers (FEL) including VUV FELs and high harmonic generation; multiphoton physics with x-ray FEL; Ultrafast atomic, molecular, cluster physics; attosecond physics; material science and imaging molecules with X-FELs; high energy density science, time-resolved absorption and x-ray scattering. The program will cover both fundamentals of high harmonic generation, soft x-ray, hard x-ray FEL and their use in spectroscopy and diffraction as well as a broad range of scientific applications. The program includes discussing new experimental techniques which need to be developed and built due to the different nature of the LCLS compared to ultrafast lasers or synchrotron sources. In addition, tours to the LCLS site will be arranged.

The goal of the School is to disseminate information about scientific opportunities in ultrafast science and train students and post docs on the new FEL facilities as well as inform researchers who are interested to join this exciting new field. Lectures will be presented by expert scientists in the various aforementioned fields. The attendees will be expected to participate in the discussions since we plan to offer these lectures in an interactive style mode to make it effective and interesting to the audience. For program information and to register see:
http://photonscience.slac.stanford.edu/pulse/uxss2007/index.php

7.   SMB XAS Short Course Wrap-Up
      (contact: S. DeBeer George, serena@slac.stanford.edu)

SMB XAS Short Course Participants

The Stanford Synchrotron Radiation Laboratory (SSRL) held a short course on x-ray absorption spectroscopy (XAS) and its applications in structural molecular biology March 13-16. The course was attended by 18 participants from across the US and Canada, and consisted of two days of lectures, followed by two days of hands-on practical sessions. Lectures covered basic theory, experimental considerations and applications. The practical sessions included hands-on data collection at SSRL beam lines 7-3 and 9-3. Participants brought in their own samples for the experiments and were able to collect preliminary data sets. There was also a full day of data analysis per group, which included data processing and fitting of EXAFS data (including single and multiple scattering analysis). Both the lectures and practical sessions were enthusiastically received by the participants. The short course was hosted by the SMB XAS group, which is funded by NIH NCRR and DOE BER.

8.   SSRL Users, Affiliates and Faculty Honored

Paul Schimmel

Paul Schimmel, professor in the Department of Molecular Biology at The Scripps Research Institute, has won the prestigious Stein and Moore Award from The Protein Society for "contributions to the highest level of the study of proteins." Schimmel's research examines the nature, origins, and boundaries of the genetic code, probing the molecular basis of tRNA specificity and the manipulative potential of tRNAs and their enzymes as tools for developing new proteins, cellular functions, and potential therapeutics. The Protein Society's Stein and Moore Award, sponsored by The Merck Company Foundation and named for Nobel laureates William Stein and Stanford Moore, venerates their contribution to understanding the connection between chemical structure and catalytic activity of the active center of the ribonuclease molecule.

Michael McGehee

Michael McGehee, assistant professor in the Department of Materials Science and Engineering (MSE) at Stanford University, has been named the 2007 Materials Research Society Outstanding Young Investigator. He is cited for "innovation and application of organic semiconductor in lasers, light-emitting diodes, transistors, and solar cells." He will deliver an award talk at the 2007 Materials Research Society Spring Meeting to be held April 9-13 in San Francisco.

Franz Himpsel

Franz Himpsel, physics professor at the University of Wisconsin Madison, has won the American Physical Society's Davisson-Germer Prize "for pioneering investigations of the electronic structure of surfaces, interfaces, adsorbates, and nanostructures." Himpsel is a pioneer in the field of surface science using synchrotron radiation. He is also a long-time user of the Synchrotron Radiation Center (SRC) in Madison and served as its Scientific Director from 1997 to 2002. Himpsel serves on the SSRL Proposal Review Panel and SSRL Scientific Advisory Committee and has also served on the ALS Science Policy Board and was just elected to the ALS Users' Executive Committee.

Zhi-Xun Shen

Zhi-Xun Shen, Stanford Professor of Applied Physics, of Physics, and of the Stanford Synchrotron Radiation Laboratory, as well as Professor of Electrical Engineering by Courtesy, has been named as the Paul Pigott Professor in the Physical Sciences. This professorship was endowed by the late Theiline Pigott McCone of Pebble Beach, California, in memory of her husband, Paul Pigott, a Stanford trustee who died in 1961. Burton Richter, Director Emeritus of the Stanford Linear Accelerator Center, is the first holder of the Pigott professorship.

9.   Upcoming Beam Time Proposal Deadlines
      (contacts: C. Knotts, knotts@slac.stanford.edu; L. Dunn, lisa@slac.stanford.edu)

The deadline for new X-ray/VUV proposals is May 1, 2007 for beam time eligibility beginning fall 2007.

July 1, 2007 is the next deadline for submitting macromolecular crystallography proposals. For beam time before fall 2007 please submit a Rapid Access proposal.

For more information about submitting a proposal for beam time at SSRL see:
http://www-ssrl.slac.stanford.edu/users/user_admin/guide.html

10.   Photon Science Job Opportunities

A number of positions are currently available at SSRL, LUSI and LCLS. Please refer to the Photon Science Job Openings page for more information about these job opportunities.
http://photonscience.slac.stanford.edu/jobs.php

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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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