CRYSTAL FARM IMAGING SYSTEM: PROTEIN STRUCTURE

这个子项目是利用由NIH/NCRR资助的共享仪器赠款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是用于拨款的，而不一定是用于调查人员的机构。描述(由申请人提供)：加州大学旧金山分校需要最先进的自动化仪器来进行晶体管理。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；其用户群在两年内翻了一番，我们预计需求将会增加。2004年，大约有140种蛋白质进行了结晶试验。使用网络计算实现晶体存储、检索和结果评估的自动化是至关重要的。随着使用该设施的科学家人数的增加，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片存储孵化系统，为用户提供预定的高分辨率水晶托盘查看、成像、评分以及图像存储和跟踪。水晶的图像可以被拍摄和存档，所有这些都不需要容易出错的人为操作水晶托盘。随着越来越多的用户争夺有限的空间，使用CF-400等设备处理错误的可能性会降低。除了预定的查看和成像水晶托盘外，当用户需要时，可以访问存储在孵化器中的任何平板。自动化晶体成像系统将允许用户远程确定应该在哪里对条件进行轻微调整，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。条码板跟踪允许集成和扩展，以适应未来增加的上游自动化系统，如纳升滴定仪。将受益于该仪器的研究包括：离子通道结构、功能和调节；运动蛋白和肌球蛋白及其调节蛋白，以了解分子如何运输细胞成分；寻找新型EG5抑制剂，一种纺锤体相关的运动蛋白，用于可能的抗癌药物开发；Hsp90，已知在调节一系列参与细胞内信号传递的蛋白质中发挥关键作用，包括核类固醇受体，如雌激素和糖皮质激素受体；以及基于结构的设计，新型抗生素耐药酶β-内酰胺酶抑制剂。与公众健康相关：这项应用涉及的研究集中在抗癌药物的开发；了解离子通道在包括大脑在内的身体区域的作用和功能；帮助类固醇受体折叠的蛋白质的研究；以及抗生素耐药酶抑制剂的设计。

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.