Contents of this Issue:
1. Science Highlight —
Two Negatives Make a Positive for Gene Therapy
(contact:
G.C.L. Wong, gclwong@uiuc.edu)
Gene therapy can potentially cure many hereditary and acquired diseases, such as cancer, hemophilia and cystic fibrosis, by delivering a healthy copy of a gene to the cells that need it. Researchers have been working on ways to deliver genes safely and effectively to the right locations. One promising approach is to use negatively charged lipids that reside in cell membranes of mammals. The idea is to pack a gene, made of DNA, into a lipid pocket, which then fuses with a cell membrane and empties the gene into the cell. The advantage of these anionic lipids (AL) is they do not evoke an immune response. The disadvantage is they do not attach well to DNA because both are negatively charged.
Researchers from the University of Illinois at Urbana-Champaign and the National Institutes of Health used x-ray techniques at BL4-2 at Stanford Synchrotron Radiation Laboratory and at the Advanced Photon Source at Argonne to investigate how to stick AL and DNA together. They made AL-DNA complexes using different kinds of positively charged ions to act as the glue. DNA could be packed into or expelled from a lipid pocket depending on the concentrations of the ions being used and the density of negative charge on the lipid. The researchers found that these different AL-DNA structures can be understood in terms of a simple theoretical model, which can serve as a recipe book for the design of the next generation of gene delivery agents.
To learn more about this research see the full technical highlight at:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/AL-DNA.html
 | |
| Schematic pictures of (A) Condensed DNA-ion-membrane lamellar structure with alternating layers of DNA and anionic membranes 'glued' together by divalent cations; (B) Condensed ion-membrane lamellar structure in which charged membranes stacks are held together by divalent cations; and (C) 2-D inverted hexagonal structure in which hexagonal arrays of divalent cations coated DNA strands wrapped in the anionic membrane monolayer tubes. |
2. Science Highlight —
Complete Reaction Cycle of a Cocaine Antibody
(contact: I.A. Wilson, wilson@scripps.edu)
 | |
| Crystal structure of the 7A1 Fab' cocaine complex with the secondary structure of the antibody light (L) and heavy (H) chains colored in cyan. Substrate cocaine is also shown in spheres with yellow carbons, blue nitrogen, and red oxygens in the active site. |
3. Science Highlight —
Structure of a SARS Protein
(contact: P. Kuhn, pkuhn@scripps.edu)
 |
To learn more about this research see the full technical highlight at:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/nsp3.html
4.
Teamwork Restores Beam in SPEAR3
(contacts:
R. Hettel, hettel@slac.stanford.edu; E. Guerra, guerra@slac.stanford.edu)
Thanks to SLAC teamwork, a problem with a high voltage power supply for the SPEAR3 booster RF system earlier which occurred on Wednesday, March 8, was rapidly addressed. Although the exact nature and severity of the problem were not readily apparent at first, the SSRL Electrical Systems and Mechanical Services groups planned for various scenarios to make anticipated repairs. Once it was determined that the power supply needed to be replaced, activities were closely coordinated with the SLAC rigging crew (CEF) to extract the supply from its storage space in PEP region 12 and with the SSRL facilities group who quickly arranged for a contractor to take down a wall in building 140 in order to access the failed power supply. Removal work was temporarily halted when an unidentified odorous gas was detected upon opening an oil inspection access port for the supply. The Industrial Safety group (ES&H) analyzed the gas and found it to be flammable, so work recommenced only after the gas had safely dissipated. The spare supply was installed by Wednesday evening and was left overnight to allow bubbles in the newly added insulating oil to escape. Electrical testing commenced on Thursday morning, but only after a special effort was made to liberate the variable voltage transformer (VVT) test cart from behind the jammed roll-up door to the PEP region 2 storage area. With SSRL users anxiously waiting for beam, those responsible for the VVT, building and labor pool, including CEP, PEP II/Accelerator Systems and CEF, quickly agreed that the VVT needed to be extracted as soon as possible, even if it meant cutting a hole in the rolling door. As it turned out, the jammed door could be opened just enough with the aid of a forklift to liberate the VVT test cart, and the power supply testing was carried out successfully. After one last hurdle involving the update of a circuit breaker arc flash hazard label, which was quickly accommodated, the booster RF system was turned on and SPEAR3 beam was re-delivered to users on Thursday afternoon, March 9. SSRL is indebted to all who participated in the replacement of the RF power supply and is grateful for the close cooperation of the SLAC groups that facilitated the repair.
 |
5. SPPS Experiment Concludes in March
(contacts: J. Hastings, jbh@slac.stanford.edu; A. Lindenberg, aaronl@slac.stanford.edu) |
Great strides have been made in the design, procurement and fabrication of Beam
Line 12-2, the new macromolecular crystallography beam line at SSRL. The
$12.35 million project is funded by a generous contribution from the Gordon and
Betty Moore Foundation through the California Institute of Technology. The
beam line is designed to allow the analysis of very small macromolecular
crystals by providing a high brightness x-ray source, superior focusing optics
and advanced crystal positioning and visualization hardware. To achieve high
brightness, SSRL's first in-vacuum undulator will be installed in the SPEAR3
ring and will take full advantage of the upgraded storage ring capabilities. A
unique modification of the SPEAR3 lattice is also being implemented to create
two independent insertion device positions in a single long straight section in
the ring. Most of the mechanical design work for the beam line is complete and
much of the hardware is being fabricated and assembled at this time. The
conventional construction project to provide a shield wall alcove is complete,
while further facility modifications needed to install the beam line are
planned for early spring. Experimental equipment to allow manipulation of very
small samples has been specified which will allow much of the current
macromolecular crystallography infrastructure to be used in the new
experimental end station. This will create a user-friendly facility capable of
advanced micro-crystal analyses as well as standard macromolecular
crystallography experiments. The beam line will be installed this summer and
is on schedule for commissioning to begin in the fall.
The SSRL Users' Organization Executive Committee (SSRLUOEC) meets throughout
the year to discuss issues of interest to the user community. Users are invited
to participate in the next meeting, which will be held on April 17. Topics for
discussion include recent user advocacy activities as well as plans for the
33rd Annual SSRL Users' Meeting (SSRL33), scheduled for October 12-13. Aaron
Lindenberg (SSRL) and Chris Kim (Chapman University), co-chairs for SSRL33,
solicit your suggestions for speakers or workshop topics--these could cover
areas of current activity at SSRL as well as exciting fields on the horizon.
Workshops on areas of mutual interest could also be conducted jointly with the
Advanced Light Source in Berkeley. Please contact anyone on the SSRLUOEC with
your suggestions or questions - we welcome your input!
Berkeley-Stanford Summer School on Synchrotron Radiation and Its Applications,
June 26-30, 2006, Berkeley, CA: The 2006 Summer School Program will be taking
place this year on the UC Berkeley campus. Detailed program and registration
information on the 2006 Summer School will be forthcoming at:
http://www.unex.berkeley.edu/eng/synchrotron/
The next deadline for new Macromolecular Crystallography proposals is April 1;
new X-ray and VUV proposals are due by May 1. For more information on the
proposal submittal, review and scheduling process, visit: http://www-ssrl.slac.stanford.edu/users/user_admin/guide.html
A number of positions are currently available at LCLS, LUSI and SSRL. Please
refer to the Photon Science Job Openings page at for more information about
these job opportunities.
__________________________________________________________________________
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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6. Progress on New Beam Line for Advanced
Micro-crystal Analysis
(contact: D. Harrington, harring@slac.stanford.edu)
7.
Using X-ray Fluorescence to Reveal Archimedes' Buried Text
(contact: U. Bergmann, bergmann@slac.stanford.edu)
The "Archimedes" experiment was online again at SSRL earlier this month.
Following upon the success of their first attempt last spring in using x-ray
fluorescence to detect traces of iron in the ink from a 10th century copy of
Archimedes' treatises (buried under medieval prayer book writings and 20th
century painting forgeries), a preservation team from The Walters Art Museum in
Baltimore brought seven additional manuscript pages to BL6-2 for more
experiments. For this data collection SSRL staff scientist Uwe Bergmann and
the team from Walters measured fluorescence from zinc and barium in an effort
to isolate the paint pigment from the ink. For more information see:
Archimedes' text and a fragment of a diagram depicting a hand.
http://today.slac.stanford.edu/feature/archimedes.asp
8.
DOE Officials Visit SLAC
(from left) Under Secretary David Garman with Doug Schwartz and
Keith Hodgson.
U.S. Department of Energy Under Secretary David Garman visited SLAC on March
22. His visit included a meeting with the DOE Site Office, discussions on the
ILC and the LCLS project, and a tour of BaBar, GLAST and SSRL. Specific tour
stops at SSRL included BLs 5, 6-2, 9-1 and 11-2 where users and staff briefly
discussed the objectives of their synchrotron-based research at SSRL.
Dr. Julie Carruthers, a science advisor in the DOE Office of Science, visited
SLAC and SSRL later that afternoon.
9. SSRL Users' Organization Executive Committee
to Meet April 17
(contacts:
J. Andrews, andrews@csueastbay.edu; C. Kim, cskim@chapman.edu;
A. Lindenberg, aaronl@slac.stanford.edu)
http://www-ssrl.slac.stanford.edu/users/ssrluo/ssrluoec-mtgs.html
Workshop on Synchrotron X-ray Scattering Techniques in Materials and
Environmental Sciences: Theory and Application, May 16-17, 2006, SSRL/SLAC,
Menlo Park, CA:
This workshop will provide a guide to planning and conducting scattering
measurements at several SSRL beam lines. Note that registration for the
practical session on the beam lines for the second day is full, but there is
still space available for the classroom discussion. Register at:
http://www-ssrl.slac.stanford.edu/conferences/workshops/scatter2006/index.php
XAFS13, July 9-14, 2006, Stanford, CA:
The 13th International Conference on X-ray Absorption Fine Structure (XAFS13)
will be held at Stanford on July 9-14. Many techniques and the theory focusing
on XAFS-related phenomena will be covered, as will applications to a wide range
of scientific areas. Register before May 1 for the early registration discount.
http://www-ssrl.slac.stanford.edu/xafs13
11. User Administration Update
(contacts:
C. Knotts, knotts@slac.stanford.edu;
L. Dunn, lisa@slac.stanford.edu)
http://www-ssrl.slac.stanford.edu/photonscience/jobs.html
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