The goal of the X-ray Crystallography Shared Facility is to provide CCC members support for research into the fine structural details of proteins, and the functional consequences of protein structures. The facility accomplishes this by providing access to critical biophysical facilities including;1) X-ray crystallographic data collection (via in-house X-ray systems and dedicated access to two synchrotron beamlines via membership in the Southeastern Collaborative Access Team (SERCAT) at Argonne Synchrotron Facility;2) highthroughput nano-crystallization for aqueous and membrane proteins;3) a novel technology (developed by the Shared Facility Director) that rapidly optimizes protein solubility and stability;4)BIAcore;5) high-throughput differential scanning and isothermal calorimetry;and 6) circular dichroism (CD). During the past funding period, the facility supported fundamental and translational research by40 CCC members, resulting in over 40 three-dimensional structures for proteins, 12 of which are cancer therapeutic targets. These investigators published 96 research articles in top peer-reviewed journals. CCC members who used the shared facility in the past five years are associated with four CCC programs: Cancer Chemoprevention, Virology, Experimental Therapeutics and Cancer Cell Biology. An example of the value added of this shared facility involves the X-ray structure of the retinoid X receptor, RXR, a protein implicated in breast cancer. The high-resolution protein structure plus complex structures of RXR bound to 14 different inhibitors directly supported the Breast SPORE program grant. This work aided the development of a lead inhibitor (UAB30) of RXR, currently in phase I human clinical trials and is continuing to support the development of second-generation inhibitors.
Specific aims of the X-ray Crystallography Shared Facility include: a) Continue to upgrade existing technologies to maintain a state-of-the-art facility and continue to incorporate novel technologies that support structural and biophysical protein characterization, b) Provide Cancer Center members with cost-effective access to several different biophysical characterization techniques to enhance basic and/or translational cancer research, c) Provide a state-of-the-art training facility to support the next generation of cancer research scientists, including graduate students and post-doctoral fellows as well as CCC faculty members, d) Continue to provide pilot/seed grants (via other non-CCC discretionary funds) to stimulate new cancer-related research. Projects are funded through competitive NIH-style peer review of proposals.
The understanding of protein structure is critical in both discovering fundamental mechanisms of cancer biology, and in developing therapeutics. The X-ray Crystallography Shared Facility supports gathering of structural and other biophysical information for CCC investigators engaged in fundamental and translational research mechanisms, prevention, and therapeutic development for cancer.
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