X-Ray Diffractometer

描述（由申请人提供）：本提案旨在为索尔克研究所结构生物学实验室的X射线衍射仪获得资金。自1994年以来，30 cm成像板（MacScience）和MacScience衍射仪一直是不断使用的工作力量。经过近13年的时间，该系统的维护成本已经很高。此外，X射线技术也取得了显著进步。我们已经完成了对理学MicroMax 007系统的测试，并将其与MacScience系统的数据质量进行了比较。新系统的效率至少是原来的10倍，我们必须尽快更换和升级该系统。X射线系统一直是索尔克研究所许多实验室的强大研究工具，通过了解生物大分子的原子结构来发展和扩大他们的前沿研究。有11个PI，包括五个主要用户，他们的研究活动需要不断访问衍射仪系统。从1994年到2006年，我们在索尔克发表了150多篇与结构相关的论文，其中包括10篇在《自然》杂志上，7篇在《科学》杂志上，2篇在《细胞》杂志上。这些研究为各个领域的进步奠定了基础，并通过完成膜受体、配体和DNA结合蛋白、代谢和工程酶、离子通道和参与信号转导的蛋白质的结构-功能研究周期，取得了开创性的发现。研究活动涉及广泛的问题。构成近70%的治疗靶点的膜蛋白的结构是最重要的（W. Kwiatkowski）。通过工程酶代谢途径设计新的治疗方法为医学提供了新的前景（J.诺埃尔，L.Wang）。β聚糖和cripto复合物的结构在开发癌症治疗中是重要的（W. Vale）。离子通道在神经系统疾病中起着重要作用（S。Choe，P. Slesinger），参与基因表达的酶也是如此（S. Pfaff）。淀粉样蛋白形成肽的结构对于理解和治疗阿尔茨海默病或帕金森病至关重要（R。Riek），最后，核激素受体的结构可用于设计肥胖治疗的激活剂（R。Evans）。检测点蛋白激酶Chk 1（T. Hunter）、氨基转移酶和油菜素类固醇结合蛋白（J. Chory）进行了研究，以了解它们的信号传导机制。

DESCRIPTION (provided by applicant): This proposal is to acquire funds for X-ray diffractometer for the structural biology laboratory at The Salk Institute. The 30 cm imaging plates (MacScience) with MacScience diffractometer have been the work force in constant use since 1994. After nearly 13 years, the system has become costly to maintain. Furthermore, the X-ray technology has advanced significantly. We have completed a test run on Rigaku's MicroMax 007 system and compared it to the data quality achievable with our MacScience system. The new system is at least 10 times efficient and it is critical for us to replace and upgrade the system as soon as we can. X-ray system has been powerful tool for research in many laboratories at the Salk Institute to develop and expand their frontier research through the understanding of the atomic structures of biological macromolecules. There are 11 PIs, including five main users, whose research activities require constant access to the diffractometer system. From 1994 to 2006, we at Salk have produced over 150 structure-related publications in leading journals including 10 in Nature, 7 in Science, 2 in Cell. These studies laid foundations for advancement in various areas and made seminal discoveries by completing the cycle of structure-function studies of membrane receptors, ligand- and DNA-binding proteins, metabolic and engineered enzymes, ion channels, and proteins involved in signal transduction. The research activities cover a wide range of questions. Structures of integral membrane proteins which constitute nearly 70% of therapeutic targets are of outmost importance (W. Kwiatkowski). Designing new therapeutics by engineering enzyme metabolic pathways gives a new prospect for medicine (J. Noel, L.Wang). The structures of betaglycan and cripto complexes are important in developing cancer therapeutics (W. Vale). Ion channels play a significant role in neurological diseases (S. Choe, P. Slesinger) as do enzymes involved in gene expression (S. Pfaff). Structures of amyloid-forming peptide are crucial to understand and treat Altzheimer's or Parkinson's disease (R. Riek) and finally structures of nuclear hormone receptors can be used to design activators for obesity treatment (R. Evans). Checkpoint protein kinase, Chk1 (T. Hunter), aminotransferase and brassinosteroid binding proteins (J. Chory) are studied to understand their signaling mechanisms.