Your protein doesn't crystallize, and your best postdocs can't concentrate it greater than ~1 mg/mL. Structural details are key to unlocking the protein's complex role in human biology. What do you do? Like thousands of other biology researchers have each year, you turn to Small Angle X-ray Scattering (SAXS). Unfortunately, 1 mg/mL is too dilute to achieve a reasonable level of detail from SAXS experiments. Fortunately, new zero-background pixel array photon- counting X-ray detectors are pushing these boundaries lower. If such a detector were available at the SIBYLS beamline, an accessible synchrotron SAXS facility, your troublesome protein could fuel your next manuscript, grant, or presentation. The SIBYLS beamline is a world class synchrotron resource for thousands of structural biologists located at the Advanced Light Source (ALS), Lawrence Berkeley National Lab. The beamline consists of two interchangeable endstations that enable researchers to perform both conventional macromolecular crystallography and SAXS experiments. SIBYLS has the only biological SAXS endstation at the ALS and is heavily subscribed, supporting a wide variety of scientists who study DNA repair, cancer, aging, immunology, virology, photosynthesis, and structural genomics. Scientists and staff at SIBYLS have implemented high throughput capabilities for SAXS data collection that have greatly impacted productivity (as measured by publication number and quality). The scientists and staff of SIBYLS have successfully provided not only a top-notch SAXS facility, but also developed new software and methods to improve SAXS data collection, processing, and analysis. As those achievements prove, our original MarCCD 165 detector (Rayonix) has performed admirably over the past seven years, but it is no longer under a service contract and is ineligible for renewal. Repairs are difficult as Rayonix no longer manufactures spare parts. Moreover, our current CCD-based detector has been rendered obsolete with the advent of modern zero- background photon counting detector technology that is better suited for SAXS data collection. We therefore propose to replace our current system with a PILATUS3 2M detector manufactured by DECTRIS. This proposal justifies our choice of detector, its integration with the existing data collection software, and the importance of the NIH-funded science that it will support. A modern detector for the SIBYLS SAXS endstation will leverage the significant investment already made in biological solution scattering at the ALS and, as a result, will rejuvenate this valuable resource for all NIH-funded researchers for years to come.

Public Health Relevance

X-ray detectors are vital to public health because they are eyes that enable scientists to calculate the shape, motion, and other details of the molecules of life (proteins, DNA, and RNA), that in turn illuminate the underlying mechanisms of cancer, aging, virology, photosynthesis, immunology, and structural genomics. At the SIBYLS beamline, a user facility providing intense X-rays and the equipment and staff needed for researchers to study these molecules, the current X-ray detector is obsolete - no longer supported by the manufacturer and exhibiting background noise properties that are detrimental to accurate experimental measurements. The pixel array detector requested, with its large area, zero background noise, high dynamic range, and rapid readout, will be invaluable to the experimental research of the hundreds of NIHfunded scientists who use the SAXS endstation at the SIBYLS beamline.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Biomedical Research Support Shared Instrumentation Grants (S10)
Project #
1S10OD018483-01
Application #
8734887
Study Section
Special Emphasis Panel (ZRG1-BCMB-U (30))
Program Officer
Levy, Abraham
Project Start
2014-09-18
Project End
2015-09-17
Budget Start
2014-09-18
Budget End
2015-09-17
Support Year
1
Fiscal Year
2014
Total Cost
$997,587
Indirect Cost
Name
Lawrence Berkeley National Laboratory
Department
Type
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720