Contents of this Issue:
1. Science Highlight - Towards a Better
Understanding of the Platelet Activation Mechanism
(contact: Kottayil I. Varughese)
When a blood vessel is cut, the body activates a repair mechanism that eventually seals the cut and prevents further blood loss. This life saving process becomes life threatening when clots form inside a functional blood vessel. Arrest of bleeding works through platelet adhesion and thrombin-induced fibrin formation at the site of injury. In order for the platelets to stick to the injured tissues and to each other, they need to be activated. Thrombin is an essential protease (a type of enzyme) that activates platelets and forms blood clots in response to vascular injury.
Researchers at The Scripps Research Institute have successfully crystallized a-thrombin with a portion of the platelet receptor GpIba, and determined the structure to a resolution of 2.3 Å. Their structural analysis shows that the thrombin uses two of its active regions, exosite I and exosite II, to bind to GpIba. There were conflicting reports in the literature favoring the binding of exosite I or exosite II to GpIba. The dual binding interaction observed in the current structure has the potential to stimulate receptor clustering on the platelet surface, thus promoting platelet signaling and activation. In addition to this, the dual mode interaction with GpIba may be an important factor in not exceeding the proper amount of clotting after a-thrombin generation at sites of vascular injury. When GpIba is bound to exosite I, it limits the pro-thrombotic function of a-thrombin by reducing its fibrinogen clotting activity.
For more information on this work see:
http://www-ssrl.slac.stanford.edu/research/highlights_archive/thrombin.html
or http://www-ssrl.slac.stanford.edu/research/highlights_archive/thrombin.pdf
2. SPEAR3 Kicks Off with Dedication Event
(contact: Keith Hodgson)
SPEAR3 is off to a tremendous start as stored current reached 100 mA on Thursday, January 22 - a major milestone in commissioning this new third generation light source. A celebratory event was held on Thursday, January 29, to recognize the contributions that hundreds of people made towards the success of the project and to dedicate the new source to the users and many staff who built the new machine. The event included introductory remarks by SLAC Director Jonathan Dorfan and presentations by Stanford President John Hennessy, Patrica Dehmer from the DOE, Amy Swain and John Norvell from the National Institutes of Health, Palo Alto Mayor Bern Beecham and SSRL Director Keith Hodgson. At the conclusion of the presentations these special guests participated in a simulation event by "loading electrons" into a hopper that together with sound, light and video simulated starting SPEAR3 and delivering beam to users. A special SPEAR3 movie featuring archival footage and interviews was created for the event. Staff and visitors also took advantage of the rare opportunity to take a guided tour inside a new accelerator. "SPEAR3 is a remarkable resource that will produce state-of-the-art science in numerous fields," says SSRL Director Keith Hodgson. "On this special occasion we recognize the people whose extraordinary teamwork made the project successful."
See also: http://www-ssrl.slac.stanford.edu/spear3/dedication.HTML
3. New Tool for Reading a Molecule's Blueprints
Announced
(contacts: Keith Hodgson;
Doug Rees)
The California Institute of Technology has received a $14,206,289 gift from the Gordon and Betty Moore Foundation to fund the building of a Molecular Observatory for Structural Molecular Biology at SSRL, or in synchrotron light source terms, a high-intensity, state-of-the-art beam line. Another separate component of this initiative is a gift to create an on-campus center at Caltech. Caltech professor Doug Rees, one of the principal investigators of the project, is excited about the observatory because "it will allow us to push the boundary of structural biology to define the atomic-scale blueprints of macromolecules that are responsible for critical cellular functions." Dr. Raymond L. Orbach, Director of the DOE's Office of Science, expressed his thanks to the Gordon and Betty Moore Foundation stating "This grant will advance the frontiers of biological science in very important and exciting ways. It also launches a dynamic collaboration between two great universities, Caltech and Stanford at a Department of Energy research facility, thereby enhancing the investment of the federal government."
The Gordon and Betty Moore foundation was established in November 2000 and funds outcome-based projects that will measurably improve the quality of life by creating positive outcomes for future generations, primarily in the areas of environmental conservation, science, higher education, and the San Francisco Bay Area.
See press release at: http://www.moore.org/news/2004/news_pr_012704microobservatory.asp or http://pr.caltech.edu/media/Press_Releases/PR12484.html
4. SPPS Progress Report
(contact: Jerry Hastings)
The Sub-Picosecond Pulse Source is in the midst of its second running period (November 18, 2003-February 18, 2004). The focus of the present period has been on measurements of the timing jitter (variation on a pulse-to-pulse basis) of the ultrafast Ti:Saph laser with respect to the electron beam and x-ray beam. The laser-electron beam jitter is measured by looking for changes in the optical behavior of a thin crystal placed near the electron beam just before the x-ray undulator. The passage of the electron beam creates a very large electric field and a laser beam from the SPPS experiment in Bldg 113, transported through a 100 m optical fiber, measures the perturbation of the thin crystal created by this pulsed electric field. The laser-x-ray jitter is measured by using a streak camera that uses a photocathode that is sensitive to both the 800 nm laser light and the 9.4 keV x-rays. Both measurements have sensitivities of order 100 fs and measure rms jitter in the 300 fs range. There is much work ongoing to cross correlate these two measurements and refine the jitter measurements.
At the same time we have, through collaboration with the European Synchrotron Radiation Facility, commissioned a Kirkpatrick-Baez (KB) double focusing mirror system. The KB focus is 1.0 x 0.5 microns2 with 2 x 106 photons per pulse. If one assumes 200 fs pulse duration this corresponds to a peak power exceeding 3 x 1012 watts/cm2 at 9.4 keV.
5. SSRL Proposal Review Panel and NIH SMB
Advisory Committee Meet
(contacts: Keith Hodgson;
Britt Hedman)
The SSRL Proposal Review Panel (PRP) held its 55th meeting on January 23-24, 2004. The PRP plays a critical role in the peer-reviewed proposal process as well as provides strategic advice and guidance on SSRL's programs and long-range planning. Several presentations were made during this meeting including: SSRL Director's Report (Keith Hodgson), SSRLUO Executive Committee Report (Benjamin Bostick), User Administration (Cathy Knotts), SPEAR3 Project and Status of Commissioning (Bob Hettel), Beam Line Development (Tom Rabedeau), SPPS Experiment (Jerry Hastings), LCLS (John Galayda), and the Materials and Chemical Science Initiative (Jo Stöhr). The PRP reviewed 59 new proposals and considered a number of proposal extension requests. Taking into consideration the transition to SPEAR3 and the short user operations run in 2004, the PRP also recommended a one-year extension for active proposals. At the closing session on Saturday, PRP Chair Russ Chianelli (UTEP) recognized the outstanding progress related to SPEAR3 and beam line development. On behalf of the PRP, Russ applauded everyone for their efforts towards the success of these projects.
The SSRL NIH Structural Molecular Biology Advisory Committee also met on Saturday to review activities and discuss strategies for the future.
6. SSRLUOEC Update
(contact: Benjamin Bostick)
The SSRL Users' Organization Executive Committee (SSRLUOEC) met on Friday, January 23, 2004. SSRLUOEC Chair Benjamin Bostick opened the meeting by summarizing recent activities of the users' organization including the annual meeting in October and updates to the user activism website (http://www.dartmouth.edu/~ssrluo/). Other presentations included an update on SSRL, SPEAR3 Commissioning Status and User Operations; Beam Line Development; and User Administration. Uwe Bergmann summarized plans for a public seminar series at SLAC and other joint activities between SSRL and SLAC users' organizations. Since SSRL users represent numerous scientific disciplines, the names of these categories were discussed and revised by the committee to more clearly reflect the breadth of user science at SSRL. The current composition of the Executive Committee includes: 3 Materials/Chemistry users; 2 Environmental/Geosciences users; 2 Molecular Biophysics users (formerly referred to as Structural Molecular Biology); 3 Macromolecular Crystallography users; 1 Ultrafast Science user (formerly referred to as LCLS); and 1 student user in any scientific discipline.
SSRLUOEC Vice-Chair Richard Brennan, OHSU, and Mike Toney, SSRL, will co-organize the 31st Annual SSRL Users' Meeting to be held on October 21-22, 2004. Users are encouraged to forward their suggestions for workshop topics, scientific sessions, or specific speakers to Dick or Mike. Mark your calendar now and plan to attend this and informative event!
(for more information see http://www-ssrl.slac.stanford.edu/users/ssrluo/)
7. User Administration Update
(contact: Cathy Knotts)
Thank you for your patience as we work through the issues related to resuming user scheduling post SPEAR3 installation. The good news is that SPEAR3 commissioning continues to progress very well; see link http://www-ssrl.slac.stanford.edu/spear3/. We expect to resume operations on many beam lines in March, paced by radiation physics approval. We have hesitated to distribute the March-April schedule until this final process has been completed, but anticipate that this will happen shortly. Our estimates of beam line availability can be found at: http://www-ssrl.slac.stanford.edu/beamlines/spear3_bl_availability.html
Because distribution of the X-ray/VUV schedule has been delayed, we postponed the deadline to submit beam time requests for the second scheduling period (May-August) until March 5, 2004. Please note that these projections remain dependent upon completion of start up and commissioning activities, and that beam stability early in the run may be difficult to predict.
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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 S ciences. Additional information about SSRL and its operation and schedules is available from the SSRL WWW site.
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