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SSRL Headlines Vol. 6, No. 6  December, 2005

Contents of this Issue:

Science Highlight — Insight into Lead Toxicity Science Highlight — Using X-ray Diffraction to See beyond the Smoke Holiday Greetings from the Director Double-focus Lattice Configuration Successfully Tested New SSRL Faculty Member SLAC Policy Committee Meeting on December 2-3, 2005 XAFS13 to be Held at Stanford July 9-14, 2006 Photon Science Job Opportunities

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1.  Science Highlight — Insight into Lead Toxicity
      (contact: J.E. Penner-Hahn, jeph@umich.edu)

Research performed at SSRL has provided insight into why lead is so damaging to the healthy development of young children. Scientists from the University of Michigan and Northwestern University used x-ray absorption spectroscopy at SSRL to understand how lead can interfere with proteins that help transform DNA blueprints into working proteins that run the body.

Gene expression proteins are the cell's contractors; they follow a gene's directions to initiate processes that will lead to building finished proteins. Many gene expression proteins contain a zinc atom that can be replaced by a lead atom if a person is exposed to too much lead. Normally, zinc attaches to four sulfur atoms, causing the protein to adopt a structure that binds to DNA. However, the researchers found that lead attaches to only three of the sulfur atoms. This difference in structure may explain the observation that when lead binds to gene expression proteins instead of zinc, the proteins do not form the proper structure and thus fail to bind properly to DNA to begin working with the blueprints.

To learn more about this research published in the July 6, 2005 issue of the Journal of the American Chemical Society see:

http://www-ssrl.slac.stanford.edu/research/highlights_archive/pb-ii.html
http://www-ssrl.slac.stanford.edu/research/highlights_archive/pb-ii.pdf

2.  Science Highlight — Using X-ray Diffraction to See beyond the Smoke
      (contact: C.D. Stout, dave@scripps.edu)

Using x-ray diffraction data collected at SSRL, Scripps researchers Jason Yano, Eric F. Johnson, C. David Stout, and their colleagues have solved the structure of a type of human P450 enzyme called CYP2A6, which is the principal enzyme in the body that degrades nicotine.

CYP2A6 is a protein that can be found in liver cells, where it is one of many enzymes responsible for removing toxic chemicals from the body. In the case of nicotine, however, CYP2A6 is responsible for breaking down approximately 80% of the chemical in the bloodstream as it circulates through the liver. With that in mind, the research team set out to solve the structure of the CYP2A6 protein with two different inhibitors (coumarin and methoxsalen) bound to it. Because they are membrane-bound proteins, this class of enzymes has been particularly difficult to work with. As a workaround, the researchers "clipped off" the end of the molecular that sits in the membrane, concentrating instead on the end of CYP2A6 that contains the iron-containing active site, the P450 heme moiety.

Their studies have revealed in fine detail the exact active site structure of the enzyme. This structural information is being used in ongoing high-resolution macromolecular crystallography experiments at SSRL to probe the active site of this P450 2A6 with additional small molecule compounds. These studies may ultimately lead to the design of an effective inhibitor of P450 2A6 that could be used to decrease the occurrence of smoking and tobacco-related cancers by reducing dependence on nicotine and by blocking formation of carcinogens.

To learn more about this research published in the September 2005 issue of Nature Structural & Molecular Biology see:

http://www-ssrl.slac.stanford.edu/research/highlights_archive/CYP2A6.html
http://www-ssrl.slac.stanford.edu/research/highlights_archive/CYP2A6.pdf
(see also: The Scripps Research Institute press release by Jason Bardi
http://www.scripps.edu/news/press/082605.html)

3.  Holiday Greetings from the Director

Dear Users, Colleagues and Friends of SSRL - as we near the end of 2005, I would like to take a moment to reflect back on the past year.

2005 was marked by a number of high points beginning with the much anticipated authorization to restart SPEAR3 on January 18 - ending a 3-month down time following an electrical accident that occurred in fall 2004. On the scientific front, research led by SSRL faculty and staff on the structure of water made the 2004 Science top 10 list.

In May, SLAC announced a major reorganization of the structure and senior management of the lab. As part of the reorganization Keith Hodgson was named Deputy Director of SLAC and Director of Photon Sciences, which includes SSRL, the science and instrument program for the LCLS, LUSI, and the Ultrafast Science Center (http://www-group.slac.stanford.edu/do/org/ps.html). During visits following the reorganization, Dr. Raymond Orbach, Director of the DOE Office of Science, and Dr. Samuel Bodman, Secretary of Energy, both complimented the SLAC staff on the numerous scientific achievements over the past 40 years and commented that they look forward to the vast possibilities that LCLS and other initiatives promise in the future.

On June 20 a significant milestone was achieved when SPEAR3 reached 500 mA for the first time. Subsequent accelerator physics periods have been used to store high current in SPEAR3 and operate Beam Line 6-2 at 500 mA. Completion of a series of beam line upgrades is the next step towards 500 mA user operations and steady progress has been made on Beam Lines 2, 7, 9 and 10 with users expected on these beam lines early in the new year. The accelerator group successfully tested a new double-focus chicane, installed in the long east-pit straight section of SPEAR3, that will be used as the source point for the new in vacuum undulator structural biology Beam Line 12 (see item 4 below).

Another major event was the 27th International Conference on Free Electron Lasers, FEL2005, held in August and hosted by the LCLS and SSRL. A broad spectrum of topics was covered as about 300 participants gathered to participate in lectures, discussions and poster sessions. SSRL looks forward to hosting an equally successful 13th International Conference on X-ray Absorption Fine Structure (XAFS13) at Stanford in July 2006 (see the announcement later in this newsletter).

October 2005 brought changes in the SSRL directorate. I became the 4th SSRL Director and Britt Hedman and Piero Pianetta jointly were appointed SSRL Deputy Directors. The new management structure can be viewed on the web under
http://www-ssrl.slac.stanford.edu/psd_organization_functional_v56.pdf.

During 2005, SSRL's Sub-Picosecond Pulse Source (SPPS) led by Jerry Hastings continued to produce exciting scientific results which were published in premier scientific journals. Details can be found at http://www-ssrl.slac.stanford.edu/jbh/. SPPS also serves as a stepping stone and training ground for the most exciting source yet to come, the Linac Coherent Light Source (LCLS). LCLS is well on track for first light in 2008, assigned to receive its full 2006 construction budget of about $80M.

I thank those who serve on SSRL's advisory committees - the Proposal Review Panel (PRP), the SMB Advisory Committee and the SSRL Users' Organization Executive Committee for their tireless work and advice. Guidance from these groups is extremely important to help us plan and move forward in the wisest and most effective ways. These advisory committees will be complemented in 2006 by a Scientific Advisory Committee (SAC), which initially will be composed of the full PRP plus additional international experts. The role of the SAC is to advise SSRL management on issues relating to the operation of SSRL as a scientific user facility and the long-term scientific directions of SSRL, including the planning and construction of new SSRL facilities.

We continue to be grateful to our funding agencies - the Department of Energy's Office of Basic Energy Sciences for providing the core operations funding and support for materials research and the DOE Office of Biological and Environmental Research and the National Institutes of Health NIGMS and NCRR Programs for support of the structural biology program. Without their effective support, we would not be able to push the scientific forefront and effectively serve our large and growing user community.

I urge you to continue to let us know your opinions and ideas - it helps us serve you better, improve our operations and plan for the future. In closing, on behalf of SSRL and its staff, let me extend our very best wishes to all of you for the holiday season and for 2006!

—Jo Stöhr, SSRL Director

4.   Double-focus Lattice Configuration Successfully Tested
      (contacts: W.J. Corbett, corbett@slac.stanford.edu; R. Hettel, hettel@slac.stanford.edu)

	Figure 1: Schematic of double-focus chicane with 10-mrad photon beam separation in SPEAR east long straight section (IVUN = in-vacuum undulator).

Along with improvements in beam brightness and orbit stability, the SPEAR3 Upgrade produced four new 4.8 m straight sections and two 7.6 m straights. Beginning in FY07, one of the 7.6 m straights will be converted to a chicane that can be used to shine light from two canted insertion devices (IDs) through the same exit port (Fig. 1). The chicane will have a "double-focus" (or "double-waist") magnetic optics configuration where the beam is vertically focused in the two chicane straight sections in order to accommodate small-gap IDs. The new optics will also reduce the vertical beam size in the 4.8-m straight sections. An in-vacuum undulator for macromolecular crystallography (Fig. 2), funded by the Moore Foundation through CalTech, will begin operation

Figure 2: In-vacuum undulator similar to that for BL12.

in FY07 in one of the double-focus locations, while a DOE-funded EPU beam line for materials science will operate in FY08 in one of the 4.8-m straight sections.

In preparation for the double-focus lattice configuration during the 2005 summer shutdown, a new ratchet wall in the SPEAR tunnel was constructed, three new quadrupole magnets with associated vacuum chamber were installed (Fig. 3), and 11 new magnet power supplies needed to realize the double-focus optics were added. The temporary magnet configuration will be used to test and characterize the double-focus machine optics during the 2006 user run. The permanent configuration, including chicane magnets and in-vacuum undulator, will be installed in the summer 2006 shutdown.

	Figure 3: Double-focus quadrupole triplet in the SPEAR east straight section.

As a first success, the accelerator group injected beam into the temporary double-focus configuration during the November 2005 start-up period. The milestone is significant because the double-focus upgrade presents challenging optics with smaller beam size and higher vertical tune. Extensive computer simulations of the new lattice predict performance similar to the original machine, but thorough investigations are needed to test optimize machine performance. Aided by a solid foundation of experience gained over the 2006 user run with the temporary lattice installation, commissioning the new BL12 in-vacuum undulator and BL13 EPU will proceed on a faster and more certain schedule. Many thanks to SSRL and SLAC staff who worked hard to meet challenging deadlines during the recent installation, and to our accelerator physics colleagues from SLAC, the ALS and the NSLS who contributed to finalizing the chicane lattice design.

5.   New SSRL Faculty Member
      (contact: B. Hedman, hedman@ssrl.slac.stanford.edu)

Ed Solomon

The SSRL faculty is pleased to welcome Edward I. Solomon, the Monroe E. Spaght Professor of Chemistry at Stanford University, as a joint appointment with Chemistry at Stanford University. Ed received his Ph.D. from Princeton University, and joined the faculty at MIT in 1975, where he became Full Professor in 1981. He became a faculty member of the Stanford University Chemistry Department in 1982. He is the recipient of numerous honors and awards, most recently the American Chemical Society Award for Distinguished Service in the Advancement of Inorganic Chemistry (which will be presented at an award ceremony in March 2006) and the election to the National Academy of Sciences in 2005. His research emphasizes the detailed application of a wide variety of spectroscopic methods combined with molecular orbital calculations to probe the electronic structure of a transition metal complex and its relation to physical properties and reactivity. Three areas of physical-inorganic and bioinorganic chemistry are of general interest: chemical and spectroscopic studies of metalloprotein active sites; detailed spectroscopic and electronic structure studies of high symmetry transition metal complexes; and the development of synchrotron spectroscopies (at SSRL) to solve important problems in inorganic and bioinorganic chemistry.

6.   SLAC Policy Committee Meeting on December 2-3, 2005
      (contact: K. Hodgson, hodgson@ssrl.slac.stanford.edu)

The meeting of the SLAC Policy Committee in early December was the first to be held with the recently revised charter that incorporates a stronger oversight role in management and environmental health and safety. This expanded role is in addition to the advice on science policy and strategic planning by the SPC. At this meeting, the SPC heard about operations during the first 6 months under the new SLAC management organization. In the Photon Science area, Keith Hodgson described the new organization and its three main elements (SSRL, the ultrafast center, and the LUSI project). Other Photon Science activities included presentations by SSRL Director Jo Stöhr on the state of SSRL, by Jerry Hastings on the LUSI project, by Keith Hodgson (representing Phil Bucksbaum) on the ultrafast science center, and by SSRL faculty chairperson Gordon Brown, Jr. on the next five-year faculty development plan. The newly formed ES&H Advisory Committee (ESHAC) reported out formally to the SPC. At the next meeting of the ESHAC, they plan to examine the user safety programs in more detail. Overall, the SPC seemed pleased with the progress and new management. The SPC reported out to Provost Etchemendy and Vice-Provost Bienenstock at the end of the two-day meeting.

7.		to be Held at Stanford July 9-14, 2006
(contacts: B. Hedman, hedman@ssrl.slac.stanford.edu; P. Pianetta, pianetta@ssrl.slac.stanford.edu)

SSRL is pleased to announce that the 13th International Conference on X-ray Absorption Fine Structure (XAFS13) will be held at Stanford, CA during the week of July 9-14, 2006. It is hosted by Stanford University and Stanford Synchrotron Radiation Laboratory. The conference venue will be on Stanford University campus in the Frances C. Arrillaga Alumni Center. The XAFS Conference constitutes an international series held every three years. The latest two XAFS conferences took place in Malmö, Sweden (2003) and Ako, Japan (2000). The scope of the conference is X-ray Absorption Fine Structure and related techniques and topics. Many techniques and the theory focusing on XAFS-related phenomena will be covered, as will applications to a wide range of scientific areas. A web site: http://www-ssrl.slac.stanford.edu/xafs13 will be continuously updated as information becomes available. Queries can be sent to the email address xafs13@ssrl.slac.stanford.edu. We look forward to your participation in this conference and seeing you here at Stanford in 2006!

8.   Photon Science Job Opportunities

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

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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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	Last Updated:	21 DEC 2005
	Content Owner:	L. Dunn
	Page Editor:	L. Dunn