THE DEVELOPMENT AND APPLICATION OF COMPLEMENTARY STRUCTURAL TECHNIQUES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在豪普特曼-伍德沃德医学研究所（HWI），我们在结构动力学，蛋白质复合物和病毒研究方面的研究领域不断发展。在本提案中，我们要求HWI工作人员和SSRL工作人员之间进行合作研究，以开发生物结构研究的三个互补领域。具体来说，我们已经使用互补结晶和SAXS方法来解决动态方面的tRNA识别复合物。我们将使用类似的跨学科SAXS和晶体学方法来确定不同的伴侣如何与相同的蛋白质复合以及对生物活性的影响。该项目需要同步辐射来扩展衍射分辨率，并需要SSRL的探测器设施来科普大型单元。我们有一个关于大脑和肺部氧化应激引起的健康相关问题的研究计划。由X射线照射引起的结构扰动是这些研究的重要组成部分。我们正在开发标记辐射引起的结构变化的方法，以推断出天然结构。我们需要使用同步辐射来确定高分辨率的细节，以发展我们的辐射模型。最后，我们正在研究病毒与核输入途径的相互作用，并开发用于全病毒高通量研究的技术。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. At the Hauptman-Woodward Medical Research Institute (HWI) we have growing research areas in structural dynamics, protein complexes, and virus studies. In this proposal we request beamtime for collaborative studies between HWI staff and SSRL staff to develop three complementary areas of biological structural research. Specifically we have used complementary crystallographic and SAXS approaches to resolve dynamical aspects in tRNA recognition complexes. We will use a similar interdisciplinary SAXS and crystallographic approach to determine how different partners complex with the same protein and the affect on biological activity. This project requires synchrotron radiation to extend diffraction resolution and the detector facilities at SSRL to cope with large unit cells. We have a program of research on health-related issues caused by oxidative stress in the brain and lungs. Structural perturbations caused by x-ray irradiation are an important part of these studies. We are developing methods to flag radiation-induced structural changes to extrapolate back to the native structure. We require the use of synchrotron radiation to determine high-resolution detail to develop our radiation model. Finally, we are investigating viral interactions with the nuclear import pathway and developing technologies for high-throughput studies of whole viruses.