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Contents of this Issue:
1. Science Highlight — Structural Genomics Identify Thymidylate Synthase Complementing Protein as a Novel Antibacterial Drug Target
(contacts: Irimpan Mathews; Ashley Deacon)
SSRL scientists have determined key binding sites in an enzyme family common to Anthrax, Botulism, Syphilis, Diarrhea and Lyme's disease. The protein x-ray crystallography data have already enabled the scientists to create a computer model of a molecule that could inhibit the enzyme's activity, which is essential for many single-celled organisms to replicate. The unique structure of the enzyme - thymidylate synthase complementing protein (TSCP) - and the recent discovery of TSCP in numerous pathogenic organisms provide an exciting opportunity for drug design. TSCP catalyzes the building of dTMP, the structure that contains "T", one of the four letters in the DNA alphabet. Cells need all four letters - A, C, G, and T - to copy themselves. TSCP is an especially attractive target for therapeutic intervention because the enzyme that performs the same task in humans is completely different, which reduces the chances of interfering with necessary cell activity in people being treated.
Research efforts centered at SSRL have elucidated the structural and functional relationship of TSCP in a high-temperature bacterium, and mapped out many of the principal binding configurations. The studies have also revealed novel features of the TSCP enzyme family. For example, a multipurpose molecule called FAD binds to TSCP differently than it does to other enzymes, making it a good spot to stop TSCP without affecting other cellular functions that use FAD in humans. A proposed design for a TSCP inhibitor has been derived from detailed analysis of the structural data [Structure, 11, 677 (2003); Editorial review: ibid, 607]. The development of specific and selective TSCP inhibitors could supply highly effective tools for therapeutic intervention with low cross reactivity against the mammalian counterpart enzyme, called thymidylate synthase (TS). This work was carried out in association with the NIH funded Joint Center for Structural Genomics (JCSG) whose structure determination core is located at SSRL.
For more information on this work see:
2. Critical Decision 2A: Approval of Long-Lead Procurement Budget for the LCLS
(contact: John Galayda)
The DOE Office of Science formalized their intent to provide $29.9M for long-lead procurements for the Linac Coherent Light Source (LCLS) in FY2005. The funds, if appropriated, will be used to procure the undulator modules, a measurement system for the undulators, a large fraction of the LCLS injector subsystems and several critical components for the linac. These funds are in addition to the Project Engineering Design and R&D allocations already planned for FY2005. Approval of CD-2A could not have been achieved without the outstanding work of the LCLS teams at ANL, LLNL and SLAC. With approval of CD-2A, LCLS remains on track for a start of x-ray laser commissioning early in FY2007 and completion of the construction project at the end of FY2008. The next major step in the DOE approval process is Critical Decision 2B, for which a review is planned in the first part of 2004. Approval of this milestone would constitute final approval of the proposed scope, cost and schedule of the entire LCLS Project. Prior to CD-2B, long-range DOE budget planning is based on a preliminary baseline range of $200M-$240M for the construction cost of the LCLS.
3. SSRL R&D Presented at the X-ray Physics Gordon Conference
(contacts: Sean Brennan; John Arthur)
Six SSRL scientists traveled to the Gordon Research Conference on X-ray Physics, held in Rhode Island during the third week of July. This biannual meeting explores the latest developments in science based on x-rays. The emphasis this year was on the use of spatially-coherent x-rays, and on the observation of ultra-fast processes with pulsed x-rays. Two SSRL scientists gave invited presentations at this conference: John Miao described his work using coherent x-rays to image micron-sized objects, including three-dimensional images of complex structures; and Jerry Hastings spoke on the use of linear accelerators as x-ray sources, with an emphasis on the new SPPS facility and the expected capabilities of the LCLS. There was much interest in the results Jerry presented from the first SPPS experimental run this past June. Several colleagues from other labs expressed surprise that an entire beam line had been built and was collecting data in less than 10 weeks.
Katharina Lüning and Sean Brennan presented a poster on work they had done in collaboration with Andy Singh, Piero Pianetta and others on both TXRF of copper-contaminated silicon wafers and on XANES of Interplanetary Dust Particles (IDPs). The poster engendered lots of lively discussion during the afternoon poster sessions.
It is clear from the many discussions with the other conference attendees that the LCLS is greatly anticipated and that the SPPS offers a unique capability in the physics of ultra-short x-ray pulses. All the participants are looking forward to the results to be presented at the next conference, to be held two years hence.
4. Senator Ted Stevens Visits SLAC and SSRL
(contact: Keith Hodgson)
On Saturday, July 19th, US Senator Ted Stevens (Alaska) visited SLAC and SSRL. Senator Stevens serves as Chairman of the Senate Appropriations Committee and of the Defense Appropriations Subcommittee and is also President Pro Tempore of the Senate. Upon his arrival, he was given an overview of the laboratory and its science programs by SLAC Director Jonathan Dorfan. Following a period of wide-ranging discussion that included new opportunities that will be enabled by DOE large facilities including LCLS, Senator Stevens visited several high energy physics experiments and facilities including the klystron gallery, PEPII and the BaBar experiment. His visit to SSRL highlighted how synchrotron radiation enables the study of many aspects of materials, illustrating the use of computer and robotic control of beam line instrumentation and sample manipulation. His visit ended with a look in three dimensions at the Anthrax lethal factor structure.
5. National Academy Committees at SLAC and SSRL
(contact: Keith Hodgson)
SLAC and SSRL recently hosted or interacted with two committees of the National Academies involved in studying facilities. On Friday, July 18, members of the Committee on Smaller Facilities visited SSRL to gather information as an aspect of its consideration of recommendations on the operations and effective utilization of small and midsize facilities. The work of this committee is charted by the National Science Foundation and DOE. The committee members met for several hours with Keith Hodgson, Jo Stöhr, Britt Hedman and Piero Pianetta. Keith gave an overview of SSRL, how it operates and its strategic vision. The committee, which had been provided written material in advance of the meeting by SSRL, asked a number of questions about how a "large facility like SSRL" operated effectively and served users in the most effective manner with the hope that some of this information might be valuable in their consideration of smaller to medium size facilities. On July 21-22, SLAC hosted a meeting of another committee of the National Academies that is developing a report on setting priorities for NSF's large scale research facility projects. Tours of SLAC and SSRL were also part of this visit and a dinner for committee members was hosted by SLAC Director Jonathan Dorfan.
6. SPEAR3 Project Continues on Track
(contact: Richard Boyce)
The SPEAR project is going well. Over 2,000 holes have been drilled and studs installed in the newly poured concrete floor. All mounting plates (~160) have been installed for the straight sections and magnet rafts with final alignment and grouting of these supports at 50% completion. Raft and straight section installation will start August 11 and cover a 3-week period followed by shielding installation. All four RF cavities have been processed and are now waiting installation. Progress in B118, SPEAR power supply room, is on schedule with all of the new motor control centers and power supply racks in place and conduit and AC distribution installation in process. Overall, the project remains on schedule thanks to a continuing effort to balance the whole schedule together with the good progress that has been made so far.
7. SRI 2003 — August 25-29, 2003
(contacts: Jo Stöhr; John Arthur)
There is still time to register to attend the 8th International Conference on Synchrotron Radiation Instrumentation (SRI 2003). SRI 2003, sponsored by SSRL and the ALS, will be held August 25-29, 2003, at the Yerba Buena Center for the Arts which is centrally located in downtown San Francisco. Visit the SRI 2003 website for the latest program information on this conference which is only held every three years. http://www.sri2003.lbl.gov/
A workshop on X-ray Science with Coherent Radiation will be held August 22-23,
2003, as a satellite meeting of SRI 2003. This 2-day workshop will explore
novel scientific applications of future coherent hard x-ray sources, including
both applications that make use of dc source properties and applications that
depend on pulsed sources.
8. SSRL Structural Molecular Biology Summer School — September 16-19, 2003
(contacts: Hiro Tsuruta; Serena George; Ana Gonzalez)
Space is still available for the lecture portion (Track 1) of the 2003 SSRL SMB
Summer School to be held here at SLAC on September 16-17 (Application deadline
is August 6). Track 1 will include presentations from experts in the fields
which will be aimed at the graduate student level, but will also be appropriate
for more experienced researchers entering the field. Sessions will focus on
the use and applications of three synchrotron x-ray techniques in studying
biological systems: Small Angle X-ray Scattering (SAXS), X-ray Absorption
Spectroscopy (XAS) and Macromolecular Crystallography (MC). In addition to the
lectures, participants in Track 2 will participate in practical rotations in
SAXS, XAS, and MC to learn data collection and analysis techniques first hand.
For more information or to apply for Track 1, visit the website.
9. 30th Annual SSRL Users' Meeting — October 9-10, 2003
(contact: Cathy Knotts)
Save the date and plan to attend the 30th Annual SSRL Users' Meeting on October
9-10, 2003. Preliminary information can be found on the meeting website:
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 S ciences. Additional information about SSRL and its operation and schedules is available from the SSRL WWW site.
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