ALSNews Vol. 228, august 20, 2003
ALSNews is a biweekly electronic newsletter to keep users and other interested parties informed about developments at the Advanced Light Source, a national user facility located at Lawrence Berkeley National Laboratory, University of California. To be placed on the mailing list, send your name and complete internet address to ALSNews@lbl.gov. We welcome suggestions for topics and content.
Previous Issues are available.
Table of Contents
- Protein Pump Reveals Secrets of Drug Resistance
- SIBYLS Beamline Taking Shape, Sees First Light
- SRI 2003 Sidelight: Saul Perlmutter on the Fate of the Universe
- UEC Corner: Notes from the Users' Executive Committee
- Submit Your Recommendations for UEC Nominees
- Who's in Town: A Sampling of ALS Users
- Operations Update
1. PROTEIN PUMP REVEALS SECRETS OF DRUG RESISTANCE
by Dan Krotz
(Contact: GMcDermott@lbl.gov)
In the race to stay one step ahead of drug-resistant bacteria, scientists from the University of California at Berkeley and Berkeley Lab obtained high-resolution structures of AcrB, a bacterial protein complex that repels a wide range of antibiotics. The structures offer new insight into how bacteria survive attacks from different antibiotics, a growing health problem called multidrug resistance. As the team learned, these robust defenses are rooted in the protein complex's remarkable ability to capture and pump out a spectrum of structurally diverse compounds. The research may inform the development of antibiotics that either evade or inhibit these pumps, allowing drugs to slip inside bacteria cells and kill them.
Read the full story at http://www-als.lbl.gov/als/science/sci_archive/64acrb.html.
Publication about this research: E.W. Yu, G. McDermott, H.I. Zgurskaya, H. Nikaido, and D. Koshland, Jr., "Structural Basis of Multiple Drug-Binding Capacity of the AcrB Multidrug Efflux Pump," Science 300, 976 (2003).
2. SYBILS BEAMLINE TAKING SHAPE, SEES FIRST LIGHT
(Contacts: SETsutakawa@lbl.gov, CBTrame@lbl.gov)
ALS Beamline 12.3.1, also called the Structurally Integrated Biology for Life Sciences (SIBYLS) beamline, achieved first light on June 27 and is currently undergoing commissioning. The new beamline, funded by the Department of Energy's Office of Biological and Environmental Research, is an essential component of a National Cancer Institute program ("Structural Cell Biology of DNA Repair Machines," or SBDR) aimed at understanding the function of dynamically assembled DNA repair machines. Understanding complex molecular machines requires an arsenal of techniques, and the SIBYLS beamline will have the unique ability to perform both protein crystallography (PX) of single crystals as well as small-angle x-ray scattering (SAXS) studies of proteins in solution. The PX capabilities will allow for the determination of protein structure using both high- and low-resolution diffraction data. SAXS can be used to identify discrete and stable complexes for crystallization trials, to provide low-resolution envelopes of their shapes, and to measure time-resolved conformational changes in proteins and macromolecular complexes in solution. Thus the combination of PX and SAXS capabilities will extend our understanding of proteins with time-resolved studies of the dynamic behavior of complex molecules.
The primary beam will be provided by the Sector 12 superconducting bend magnet. Two monochromators will be available: one for PX using high-resolution Si(111) crystals (5.5 - 17 keV) and another for SAXS using high-throughput multilayer mirrors (7 - 13 keV). The PX endstation will include an ADSC Q315 CCD detector, a gantry system for positioning of the detector relative to the sample, a beam diagnostics system, and many design features that have been successfully incorporated into other ALS beamlines. The SAXS endstation will include equipment allowing both static and time-resolved SAXS measurements: a Mar CCD165 detector, an Opotek VIBRANT 355 II tunable laser system, and a Unisoku mixing cell with 1.5-ms mixing times.
The interchange between the PX and SAXS endstations will be simple, and users will have the capability to do both types of experiments during one visit to the beamline. The inherent flexibility of the SIBYLS beamline design will allow for the maximization of the information collected from any individual sample, which is critical because sample preparation, not the speed of data collection, will be the limiting factor. This flexibility will allow researchers to bridge the gap between low-resolution studies of large protein complexes (using electron-microscope and SAXS techniques) and atomic-resolution single-crystal diffraction studies that advance the interpretive framework for molecular and cellular biology. The SIBYLS beamline will provide a critical facility for structural studies of macromolecular assemblies, not only for the SBDR project, but also for the greater scientific community.
John Tainer and Priscilla Cooper (Life Sciences Division) are the lead research scientists, aided by SAXS consultant Hiro Tsuruta (Stanford Univ.) and collaborator James Holton (Physical Biosciences Division). Beamline design and construction was done in collaboration with an ALS scientific and engineering team led by Alastair MacDowell (ALS Experimental Systems Group). The PX endstation will begin sample testing in October 2003, and the SAXS endstation is scheduled to begin first test data collection in September 2003. Additional information about SIBYLS can be found online at http://www.sibyls.org/ and http://www.sbdr.lbl.gov/.
3. SRI 2003 SIDELIGHT: SAUL PERLMUTTER ON THE
FATE OF THE UNIVERSE
(Contact: EJMoxon@lbl.gov)
Will the universe last forever, or will it someday come to an end? Attendees of SRI 2003 looking for a little diversion will have the opportunity to hear Berkeley Lab astrophysicist Saul Perlmutter, leader of the Supernova Cosmology Project (SCP), speak on "Supernovae, Dark Energy, and the Accelerating Universe" at 7:00 P.M. on Wednesday, August 27, at the Yerba Buena Center for the Arts Theater (where SRI 2003 plenary sessions will be held). The talk is free and open to the public.
Surprisingly, the apparently philosophical question about the fate of the universe can be answered empirically. Light from the cataclysmic explosions of distant stars—supernovae—provides us with natural mile markers that can be used to track the past expansion of the universe and extrapolate its fate. The most recent results are unsettling, at least to physicists. It appears that the universe will last forever, and that its expansion will speed up indefinitely. If so, some fundamental physics concepts may need to be revised, and some mysterious "dark energy"—perhaps Einstein's "cosmological constant"—may pervade the universe. This is the first decade in which we can begin to answer such cosmological questions with a variety of measurement techniques. Science magazine named SCP measurements of the accelerating universe the 1998 "Breakthrough of the Year." For more about the speaker and venue, go to http://www.sri2003.lbl.gov/html/publicscience.html.
4. UEC CORNER: NOTES FROM THE USERS' EXECUTIVE
COMMITTEE
by Jennifer Doudna
(Contact: doudna@uclink.berkeley.edu)
Greetings from the UEC. At our meeting on July 16, we discussed several topics of current interest to users. Greg Denbeaux reported that the users' lobbying trip to Washington in April was highly successful, raising awareness among our Congressional reps of the exciting science carried out at synchrotrons around the country. It was suggested that a letter-writing campaign in support of increased funding for synchrotron research could be coordinated through the UEC, and this will be discussed further at our upcoming Users' Meeting in October. Progress on the planned ALS upgrades include a two-step schedule, beginning with an increase in the time-averaged curent by a factor of three and a move to "top-off" mode injection of the ring. Following these changes, new insertion devices and beamlines will be phased in. The UEC agreed that these changes will benefit the entire user community and will also discuss the changes at our upcoming October meeting. Finally, planning for the new user building and housing are under way, and the UEC reviewed current drafts of the user building layout.
Users are encouraged to check out the Web site for the upcoming Users' Meeting October 6-8 (http://www-als.lbl.gov/als/usermtg/) and plan to attend. Five exciting workshops will focus on recent advances in microscopy, molecular environmental sciences, x-ray crystallography, materials science, and inelastic x-ray scattering. We'll see you there!
5. SUBMIT YOUR RECOMMENDATIONS FOR UEC NOMINEES
(Contact: AMGreiner@lbl.gov)
The UEC is currently seeking recommendations from ALS users for nominees to be placed on the ballot for this fall's UEC election. Note that these are not direct nominations; a UEC committee will consider these recommendations in drawing up a candidate list. Direct nominations from members of the ALS Users' Association may also be made by petition on an official nomination form. These require the signed endorsement of five Users' Association members and must be mailed or turned in at the upcoming Users' Meeting in October. A simple online form for recommendations as well as a downloadable nomination form (in PDF format) can be found at the UEC election Web site (http://www-als.lbl.gov/als/uec/vote/).
The deadline for submitting recommendations is September 22, and the deadline for submitting signed nomination forms is October 8. The final slate of candidates will be announced on the election Web site on October 14. Voting will take place online from October 14 to November 14, and the results will be posted on November 18. The newly elected UEC members will take office for a three-year term beginning in January 2004 and ending in January 2007.
6. WHO'S IN TOWN: A SAMPLING OF ALS USERS
Following are some of the experimenters who will be collecting data during the next two weeks at the ALS. (The ALS will be running in two-bunch mode August 12 through 24.)
Beamline 1.4.3
John Bradley (Lawrence Livermore National Laboratory)
Dan Fried (Univ. of California, San Francisco)
Beamline 4.0.2
Nora Berrah (Western Michigan Univ.)
Jo Stohr (Stanford Synchrotron Radiation Laboratory)
Boris Sinkovic (Univ. of Connecticut)
Beamline 5.3.2
Adam Hitchcock (McMaster Univ., Canada)
Harald Ade (North Carolina State Univ.)
Beamline 7.0.1
James Allen (Univ. of Michigan)
M. Zahid Hasan (Princeton Univ.)
Sergei Butorin (Uppsala Univ., Sweden)
Beamline 7.3.3
Ersan Ustundag (California Institute of Technology)
Beamline 8.0.1
Dennis Lindle (Univ. of Nevada, Las Vegas)
David Sherman (Univ. of Bristol, UK)
Beamline 9.0.2
Tomas Baer (Univ. of North Carolina)
Beamline 9.3.2
Suntharampillai Thevuthasan (Pacific Northwest National Laboratory)
Beamline 10.0.1
David Pegg (Univ. of Tennessee)
Beamline 10.3.1
Eleanor Blakely (Berkeley Lab)
Beamline 10.3.2
Andrei Istratov (Berkeley Lab)
7. OPERATIONS UPDATE
(Contact: Lampo@lbl.gov)
For the user runs of August 5 - 10 and 12 - 18 (two-bunch mode), the beam reliability (time delivered/time scheduled) was 99%. Of the scheduled beam, 98% was delivered to completion without interruption. There were no significant outages.
Long-term and weekly operations schedules are available on the Web (http://www-als.lbl.gov/als/schedules/index.html). Requests for special operations use of the "scrubbing" shift should be sent to Bruce Samuelson (ALS-CR@lbl.gov, x4738) by 1:00 p.m. Friday. The Accelerator Status Hotline at (510) 486-6766 (ext. 6766 from Lab phones) features a recorded message giving up-to-date information on the operational status of the accelerator. A Web page showing the ring status in real time can be found at http://www-als.lbl.gov/als/status/.
ALSNews is a biweekly electronic newsletter to keep users informed about developments at the Advanced Light Source, a national user facility located at Ernest Orlando Lawrence Berkeley National Laboratory, University of California. To be placed on the mailing list, send your email address to ALSNews@lbl.gov. We welcome suggestions for topics and content. Submissions are due the Friday before the issue date.
LBNL/PUB-875
Editors: lstamura@lbl.gov, alrobinson@lbl.gov, amgreiner@lbl.gov
This work was supported by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC03-76SF00098.