CRYSTAL FARM IMAGING SYSTEM: PROTEIN STRUCTURE

该子项目是利用由NIH/NCRR资助的共享仪器补助金提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是资助机构，不一定是研究者的机构。描述（申请人提供）：加州大学旧金山分校需要最先进的晶体管理自动化仪器。我们目前的x光设备由14个独立实验室和70多名员工使用；它的用户群在两年内翻了一番，我们预计需求会增加。2004年，大约有140种蛋白质进行了结晶试验。利用网络计算实现晶体存储、检索和结果评估的自动化至关重要。随着使用该设施的科学家数量的增加，有效利用空间和仔细监测和组织实验已成为一个紧迫的目标。DPI CF-400是一种400板存储孵化系统，可为用户提供预定的高分辨率晶体盘查看、成像、评分以及图像存储和跟踪。晶体的图像可以拍摄和存档，所有这些都没有容易出错的人工操作晶体托盘。随着越来越多的用户争夺有限的空间，使用CF-400这样的设备，处理错误的可能性降低了。随着晶体托盘的预定查看和成像，访问任何板存储在培养箱是可用的，当用户需要它。自动晶体成像系统将允许用户远程确定应该对条件进行轻微调整的位置，从而提供更快的晶体生长条件优化，并最终加速所有研究项目。条形码板跟踪允许集成和可扩展性，以适应未来增加的上游自动化系统，如纳升液滴设置器。将受益于该仪器的研究包括离子通道的结构、功能和调节；运动蛋白和肌凝蛋白及其调节蛋白，以了解分子如何运输细胞成分；寻找新的Eg5（一种纺锤体相关的运动蛋白）抑制剂，以开发可能的抗癌药物；Hsp90，已知在细胞内信号传导的一系列蛋白调控中发挥关键作用，包括核类固醇受体，如雌激素和糖皮质激素受体；以及基于结构的新型耐药酶-内酰胺酶抑制剂设计。与公共卫生相关：本申请涉及的研究重点是抗癌剂的开发；了解包括大脑在内的身体各部位离子通道的作用和功能障碍；类固醇蛋白学：对协助类固醇受体折叠的蛋白质的研究；以及抗抗生素酶抑制剂的设计。

This subproject is one of many research subprojects utilizing the resources provided by a Shared Instrumentation Grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the grant, which is not necessarily the institution for the investigator. DESCRIPTION (provided by applicant): UCSF is in need of state-of-the-art automated instrumentation for crystal management. Our current X-ray facility is used by fourteen independent labs and over seventy people; its user group has doubled over two years, and we anticipate increased demand. About one hundred forty proteins were subjected to crystallization trials in 2004. Automation of crystal storage and retrieval and evaluation of results using network computing is vital. As the number of scientists using the facility increases, efficient use of space and careful monitoring and organization of experiments has become an urgent goal. The DPI CF-400 is a 400- plate storage incubation system that provides users scheduled, high-resolution crystal tray viewing, imaging, scoring, and image storage and tracking. Images of crystals can be taken and archived, all without error- prone human manipulation of crystal trays. As more users vie for limited space, the probability of handling errors is reduced with a device such as the CF-400. Along with scheduled viewing and imaging of crystal trays, access to any plate stored in the incubator is available when a user demands it. The automated crystal imaging system will allow users to remotely determine where slight adjustments to conditions should be made, thus providing faster optimization of crystal-growth conditions and ultimately accelerating all research projects. Barcode plate tracking allows for integration and expandability to accommodate future addition of upstream automated systems, such as nanoliter drop setters. Studies that will benefit from this instrument include ion-channel structure, function, and regulation; kinesins and myosins and their regulatory proteins to learn how molecules transport cellular components; search for novel inhibitors of Eg5, a spindle- associated kinesin, for possible development of anti-cancer agents; Hsp90, known to play a critical role in the regulation of a broad array of proteins involved in intracellular signaling including nuclear steroid receptors such as the estrogen and glucocorticoid receptors; and structure-based design of novel inhibitors of the antibiotic-resistant enzyme beta-lactamase. Relevance to public health: The research involved in this application is focused on the development of anti-cancer agents; understanding the roles and malfunctions of ion channels in areas of the body including the brain; the study of proteins that assist in the folding of steroid receptors; and the design of inhibitors to antibiotic-resistant enzymes.