**** **** **** * * * * * * **** **** **** * * * * * * **** **** * * **** HEADLINES - a digital monthly publication
Contents of this Issue:
1. Science Highlight — Protecting against Cocaine, Heroin, and Sarin Gas
(contact: Matthew Redinbo, University of North Carolina at Chapel Hill)
SSRL has played an important role in characterizing a family of enzymes that detoxify heroin and cocaine, and have the potential to metabolically eliminate the nerve poisons sarin, soman, and tabun, which have claimed thousands of lives. Using x-ray crystallographic data, the Redinbo group at the University of North Carolina at Chapel Hill has uncovered the specific and general ways the carboxylesterase enzymes bind to those dangerous substances. This new understanding of the structure-function relationships will be of very significant value in designing drugs to combat overdoses, terrorist attacks and chemical warfare. Redinbo's group is working on developing more specific and faster versions of the human form of the enzyme (hCE1) to inject into people who have overdosed on heroin and cocaine and into soldiers potentially facing nerve gas attacks.
Carboxylesterases in mammals are responsible for breaking down a wide variety of human-made drugs and foreign chemicals, and may have evolved to safely process the chemicals many plants use to protect themselves. The first crystallographic study of hCE1 bound to cocaine- and heroin-like compounds revealed important molecular details about how the drugs are metabolized and how the enzyme can recognize such structurally diverse compounds. Redinbo's group found that the hCE1 active site contains both a specific compartment (that binds with specific features of a compound, the way Lego pieces fit together), and a promiscuous compartment (that can bind with many shapes, the way gum sticks to many surfaces). These features enable the enzyme to act on structurally distinct chemicals like dangerous narcotics and weaponized nerve agents.
For more information on this work see:
2. X-ray Absorption Spectroscopy Catches the Chemical Form of Mercury in Fish - SSRL Scientists Reveal New Findings in Science Article
(contact: Graham George)
The presence of "methyl mercury" in fish is well-known, but until now the detailed chemical identity of the mercury has remained a mystery. In an x-ray absorption spectroscopy study published in the August 29 issue of Science (Science 301, 2003: 1203; http://sciencenow.sciencemag.org/cgi/content/full/2003/828/3), SSRL scientists report that the chemical form of mercury involves a sulfur atom (most likely in a so-called aliphatic form). The study presents significant new knowledge - because the toxic properties of mercury (or any element) are critically dependent upon its chemical form - and represents an important milestone in developing an understanding of how harmful mercury in fish might actually be. The study was carried out by SSRL staff scientists Ingrid Pickering and Graham George and postdoctoral fellow Hugh Harris using SSRL's structural molecular biology beam line 9-3. The very high flux, excellent beam stability and state-of-the-art detector technology allowed the team to measure samples of fish containing micromolar levels of mercury, much lower than had previously been possible. Funding for this research was provided by the U.S. Department of Energy, Office of Biological and Environmental Research and by the NIH National Center for Research Resources, Biomedical Technology Program. (Ingrid Pickering and Graham George have recently relocated to the University of Saskatchewan and Hugh Harris to the University of Sydney).
3. Final Phase of the SPEAR3 Installation on Schedule
(contact: Tom Elioff)
The final installation phase of the SPEAR3 project continues on schedule -- only 2 months remain for planned project completion. The final magnet/vacuum raft assembly was installed on August 27 at 15:30, completing the magnetic lattice for SPEAR3. Due to the hard work of many staff and external contract workers, the 54 raft assemblies (weighing more then 1,250,000 lbs) were successfully rolled into SPEAR and placed onto precision pins over a period of only 13 working days beginning August 11. In addition, the majority of the new power supplies have been tested and installed, the new beam line front-ends are in place (except for BL10), the RF klystron power supply, loads, and waveguides are installed, all 4 new RF cavities have been received and checked-out, the bellows and vacuum straight section components are nearing completion, and injection system components are complete. Remaining work in the coming months includes final low conductivity water (LCW) connections to the magnet rafts, LCW piping and connection to the RF system, AC power connections to power supplies, DC connections to power supplies and to magnet rafts in the tunnel, Klystron installation and check-out, RF cavity installation in the ring and installation and testing of remaining instrumentation and control system components. The work should be complete and the ring closed down by early November at which time accelerator and vacuum commissioning will commence. Those interested can view time lapsed video clips of the SPEAR3 installation process by visiting the SSRL home page at: http://www-ssrl.slac.stanford.edu/ and clicking on the video links. SPEAR3 is indeed on schedule to begin to deliver its significant benefits to users in early 2004.
4. Registration Extended for SSRL SMB Summer School
(contacts: Hiro Tsuruta; Serena George; Ana Gonzalez)
The application deadline for the lecture portion only of SSRL's 2003 Structural
Molecular Biology Summer School has been extended until September 3. This
track 1 of the Summer School, which will be held September 16-17, will include
presentations from experts 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 including: small angle x-ray scattering, x-ray
absorption spectroscopy, and macromolecular crystallography. For more
information visit the website:
5. Call for Nominations for 6th Annual Lytle Award
(contact: Cathy Knotts)
Users are encouraged to submit nominations for the 2003 Farrel W. Lytle Award, which consists of a $1,000 award and a plaque that is displayed in the User Research Administration Office at SSRL. This award was established by the SSRL Users' Organization Executive Committee (SSRLUO-EC) to promote technical or scientific accomplishments in synchrotron radiation-based science and to foster collaboration and efficient use of beam time among users and staff at SSRL. Previous awardees include: Farrel W. Lytle, Tom Hostetler, Roger Prince, Britt Hedman, and Paul Phizackerley. Nominations should be sent to Cathy Knotts, SSRL User Research Administration Manager, by September 8, 2003.
6. Nominations for the SSRLUO-EC
(contact: Cathy Knotts)
The September 15 deadline for nominating SSRL users for the 2004 Users' Organization Executive Committee is fast approaching. Nominations are needed for vacant positions in materials/chemistry, environmental/geosciences, structural molecular biology, and macromolecular crystallography. Nominations are also needed for a graduate student member of the committee (in any of the disciplines listed). The final voting will be held at SSRL's Annual Users' Meeting. http://www-ssrl.slac.stanford.edu/conferences/ssrl30/ ssrluoec_nominations.html
7. Several Workshops Planned for October 8, 2003
(contact: Cathy Knotts)
If you haven't already done so, register for SSRL's Annual Users' Meeting by
September 29 to take advantage of early registration discounts ($75 regular;
$25 students). Held on October 9-10, this meeting will focus on a variety of
synchrotron-based techniques of interest to the broad scientific community of
synchrotron users. Meeting sessions will focus on interdisciplinary
applications of small angle x-ray scattering, macromolecular crystallography,
microspectroscopy and diffraction, and surface spectroscopy. The Users'
Meeting provides a forum for the presentation and discussion of research
activities from SSRL and the synchrotron community. New data and developments
will be shared through invited talks and poster presentations. Find
registration and additional information on the meeting website:
Call for Posters and Graduate Student Poster Competition: Abstracts for the
poster session can be submitted through September 22 for inclusion in the
program material. Poster presentations will be displayed throughout the Users'
Meeting and will be highlighted during a poster session on October 9. Graduate
students are encouraged to submit posters of their work and are eligible to
compete for poster prizes. Graduate students who wish to participate in this
competition must be registered to attend the Users' Meeting, and must indicate
that they are participants in the graduate student poster competition on the
poster abstract submission form. Prizes include a monetary award and a ribbon.
Poster instructions are available on the website:
Special Session to Honor Iran Thomas: In tribute to the late Iran Thomas of the U.S. Department of Energy's Office of Science, a special session at the Users' Meeting has been organized to honor Thomas' interest in education and diversity. Thomas, who passed away on February 28, was a long-time director in the Office of Basic Energy Sciences who supported and enabled the development of new and innovative research programs, including the University of Texas El Paso (UTEP) and SSRL Gateway program. This special session, PERSPECTIVES ON THE UTEP-SSRL GATEWAY PROGRAM, will be held on Thursday, October 9, and will include several presentations from students in the Gateway program.
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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