Thursday, May 1, 2025
5/1/2025
Upgrade of a Core Laboratory Macromolecular X-ray Diffraction System - Project Summary The aim of this Shared Instrumentation Grant proposal is to enhance capabilities for macromolecular X- ray crystallography at the University of Texas Health Science Center at San Antonio (UT Health) X-ray Crystallography Core Laboratory (XRC), located in the Department of Biochemistry & Structural Biology within the Joe R. and Teresa Lozano Long School of Medicine. The XRC has a 20-year history and is an Institutional Research Core under the Office of the Vice President for Research and part of the Drug Discovery & Structural Biology Shared Resource under the NCI-designated Mays Cancer Center. It provides crystallization, X- ray diffraction data collection and macromolecular structure determination services for a wide variety of projects throughout the institution, its centers and the San Antonio area. Users for the instrumentation are investigators for topics such as cancer biology, DNA damage and repair, innate immunity, infectious disease, and drug design to name a few. Current resources in the XRC include a MicroMax 007HF X-ray generator driving two ports with VariMax-HR and HF confocal optics aimed at two mounted R-AXIS HTC imaging plate detectors. The 007HF rotating anode generator has faithfully served XRC users and will be functional and supported for years to come by the manufacturer Rigaku (in business since 1951). However, the imaging plate detectors have been phased out by Rigaku and are no longer eligible for parts support beginning this year. To both continue and enhance XRC operation, we propose to upgrade/replace the two detectors and optics with a single HyPix- 6000HE photon counting detector mounted on a Universal Kappa Goniometer and a VariMax VHF confocal microfocus optic with a continuously adjustable divergence slit assembly. The new instrumentation will be mounted on the existing X-ray generator, taking the place of both obsolete imaging plate systems, and will also use the existing Oxford Cryostream 800 cooling system. The imaging plate technology is two generations behind in technology, superseded by charge coupled device (CCD) detectors and now photon counting detectors. The HyPix-6000HE significantly outperforms imaging plate technology and improves upon CCD technology in that photon counting detectors have high sensitivity and dynamic range while eliminating error due to readout noise and dark current. Additional major advantages are the speed and volume of data that can be acquired by photon counting detectors over our imaging plates. The HyPix-6000HE can acquire full datasets in the timescale of minutes to hours while the image plates require hours to days. Overall, the requested upgrade to the XRC will benefit investigators with rapid, high quality, high resolution data collection to accomplish structure determinations of macromolecules relevant to human health in short order.
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