X-Ray Crystallography

X射线晶体学

• 批准号: 8732234
• 负责人: EDWARD E. PARTRIDGE
• 金额: $ 17.54万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-28 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8732234
• 关键词: Binding; Biological; Breast; Calorimetry; Cancer Biology; Cancer Center; Cellular biology; Circular Dichroism; Clinical Trials; Complex; Comprehensive Cancer Center; Crystallization; Data Analyses; Data Collection; Development; Equipment; Faculty; Funding; Generations; Goals; Grant; Health Services Accessibility; Housing; Human; Journals; Knowledge; Lead; Malignant Neoplasms; Membrane Proteins; Methods; Molecular; Peer Review; Phase; Postdoctoral Fellow; Preparation; Prevention; Proteins; Publishing; RXR; Research; Research Personnel; Research Support; Resolution; Roentgen Rays; Role; Sampling; Scanning; Scientist; Seeds; Site; Solubility; Structure; Synchrotrons; System; Techniques; Technology; Therapeutic; Three-dimensional analysis; Training; Translational Research; United States National Institutes of Health; Work; X-Ray Crystallography; anticancer research; aqueous; base; beamline; cancer cell; cancer chemoprevention; cost effective; fundamental research; graduate student; improved; inhibitor/antagonist; macromolecule; malignant breast neoplasm; member; nano; new technology; next generation; programs; protein structure; protein structure function; therapeutic development; therapeutic target; three dimensional structure; tool; virology

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.

X 射线晶体学共享设施的目标是为 CCC 成员的研究提供支持 蛋白质的精细结构细节，以及蛋白质结构的功能后果。设施 通过提供关键生物物理设施的使用来实现这一目标，包括： 1) X射线晶体学数据 收集（通过内部 X 射线系统和通过会员资格专用于两条同步加速器光束线的访问 在阿贡同步加速器设施的东南协作访问团队 (SERCAT) 中； 2）高通量 水蛋白和膜蛋白的纳米结晶； 3）一项新技术（由 共享设施总监），快速优化蛋白质溶解度和稳定性； 4）BIA核心； 5）高通量 差示扫描和等温量热法； 6)圆二色性(CD)。过去期间 资助期间，该设施支持 40 个 CCC 成员的基础和转化研究，结果 超过 40 种蛋白质三维结构，其中 12 种是癌症治疗靶点。这些 研究人员在顶级同行评审期刊上发表了 96 篇研究文章。使用过的 CCC 会员 过去五年的共享设施与四个 CCC 项目相关：癌症化学预防、 病毒学、实验治疗学和癌细胞生物学。此共享的附加值示例 该设施涉及类视黄醇 X 受体 RXR 的 X 射线结构，RXR 是一种与乳腺癌有关的蛋白质。这 高分辨率蛋白质结构以及直接与 14 种不同抑制剂结合的 RXR 复杂结构 支持乳房孢子计划拨款。这项工作有助于开发一种先导抑制剂 (UAB30) RXR，目前正在进行一期人体临床试验，并继续支持第二代的开发 抑制剂。 X 射线晶体学共享设施的具体目标包括： 升级现有技术以维持最先进的设施并继续融入新颖的技术 支持结构和生物物理蛋白质表征的技术，b) 提供癌症中心 成员可以经济有效地获得几种不同的生物物理表征技术，以增强 基础和/或转化癌症研究，c) 提供最先进的培训设施以支持下一步 一代癌症研究科学家，包括研究生和博士后研究员以及 CCC 教职人员，d) 继续提供试点/种子补助金（通过其他非 CCC 可自由支配资金） 刺激新的癌症相关研究。项目通过 NIH 式的竞争性同行评审获得资助 提案。