X-Ray Diffractometer

描述(申请人提供)：本提案旨在为索尔克研究所的结构生物学实验室获得X射线衍射仪的资金。带有MacScience衍射仪的30厘米成像板(MacScience)自1994年以来一直在使用。近13年后，该系统的维护成本变得很高。此外，X射线技术也有了很大的进步。我们已经在Rigaku的MicroMax 007系统上完成了测试运行，并将其与我们的MacScience系统所能达到的数据质量进行了比较。新系统的效率至少提高了10倍，对我们来说，尽快更换和升级系统至关重要。X射线系统已经成为索尔克研究所许多实验室通过了解生物大分子的原子结构来发展和扩大其前沿研究的有力工具。有11个个人投资机构，包括5个主要用户，其研究活动需要经常使用衍射仪系统。从1994年到2006年，我们索尔克在领先期刊上发表了150多篇与结构相关的文章，其中10篇发表在《自然》杂志上，7篇发表在《科学》杂志上，2篇发表在《细胞》杂志上。这些研究为各个领域的发展奠定了基础，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。研究活动涵盖了广泛的问题。构成近70%治疗靶点的完整膜蛋白的结构是最重要的(W.Kwiatkowski)。通过设计酶代谢途径来设计新的治疗方法为医学提供了新的前景(J.Noel，L.Wang)。Betaglycan和Cripto复合体的结构在开发癌症治疗药物中很重要(W.Vale)。离子通道在神经系统疾病(S.Choe，P.Slesinger)和参与基因表达的酶(S.Pfaff)中发挥着重要作用。淀粉样蛋白形成肽的结构对于理解和治疗阿尔茨海默氏症或帕金森氏病至关重要(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)。对Checkpoint蛋白激酶、Chk1(T.Hunter)、转氨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.