LIQUID HANDLING SYSTEM FOR HTP CRYSTALLIZATION

描述(由申请人提供)： 该提案的目标是升级Hauptman-Wooodward医学研究所(HWL)的高通量(HTP)结晶实验室。结构基因组学和结构生物学都朝着三维X射线晶体结构测定的HTP方法发展。这些结构被用作了解分子相互作用的结构和功能之间的关系的工具，并为合理的药物设计提供宝贵的信息。结晶条件的确定是成功的先决条件。在广泛的溶液条件下快速执行和分析大量实验的能力增加了成功结晶的可能性。HTP结晶实验室有能力建立和记录在1536孔微量分析板中进行的微批结晶实验的结果。所要求的升级是为了设置这些实验所用的关键设备：液体处理系统(LHS)。Apogent Discovery(前身为Robbins Science)Hydra 96和Hydra 384 LHS目前用于向1536孔HTP结晶微量分析板输送油、结晶鸡尾酒解决方案和蛋白质解决方案。此次升级是为了购买一台Apogent Disfinies Tango LHS。Tango在设计和操作上与九头蛇非常相似，它将有效地整合到实验室的结构中。它提供了一个全自动化的板材输送平台和更快的输送速度。这将减少结晶装置的技术监督所需的时间；增加设施的能力；使我们能够每天建立更多的样品。在样品供应有限的情况下，Tango将建立结晶板，使用的蛋白质减少42%。我们已经确定了一个内部咨询委员会，以帮助首席调查员处理与高通量实验室的科学管理有关的事项。委员会将确保以下用户群体得到公平的服务：结构生物学-900/年，结构基因组-800/年，以及制药-300/年

DESCRIPTION (provided by applicant): The goal of this proposal is to upgrade the High Throughput (HTP) Crystallization Laboratory at the Hauptman-Wooodward Medical Research Institute (HWl). Structural genomics and structural biology have both moved toward HTP methods for three-dimensional X-ray crystal structure determination. These structures are used as tools for understanding the relationship between the structure and function of molecular interactions and provide invaluable information for rational drug design. The identification of crystallization conditions is a prerequisite for success. The capacity to rapidly execute and analyze a large number of experiments under a wide range of solution conditions increases the likelihood of successful crystallization. The HTP Crystallization Lab has the capacity to set up and record results for microbatch crystallization experiments held in 1536-well microassay plates. The requested upgrade is for a key piece of equipment used to set up these experiments: the liquid handling system (LHS). Apogent Discoveries (formerly Robbins Scientific) Hydra 96 and Hydra 384 LHSs are currently in use to deliver oil, crystallization cocktail solutions, and protein solutions to 1536-well microassay plates for HTP crystallization. The upgrade is for the purchase of an Apogent Discoveries Tango LHS. The Tango is sufficiently similar in design and operation to the Hydra that it will efficiently integrate into the structure of the lab. It offers a fully automated platform for plate delivery and much faster deliveries. This will reduce the time required for technical oversight of the crystallization setups; increase the capacity of the facility; allow us to set up more samples/day. In cases where the sample is in limited supply, the Tango will set up crystallization plates using 42% less protein. We have identified an internal advisory committee to help the principal investigator with matters relevant to the scientific administration of the High Throughput Laboratory. The committee will insure the following user groups are equitably served: structural biology-900/yr, structural genomics-800/yr, and pharma-300/yr