A High Throughput, High Content Screening System for Northwestern University

描述（由申请人提供）：当代生命科学研究已经看到了允许高度并行分析的方法的日益集成。随着全基因组 RNAi 集合的出现，基因组序列的完成驱动了基因功能的表征，其重要性已达到新的水平，该集合允许大规模消除后生动物基因功能。表型的微观评估通常代表这些方法的一个令人衰弱的限速步骤，因此高通量研究通常以简单的光度测量结束。由于生物学的大部分依赖于对细胞的直接观察，因此开发允许对细胞形态进行定量高通量分析的方法引起了相当大的兴趣。西北大学新建立的高通量分析设施是一个共享资源中心，使学术研究人员能够开展涉及大规模自动化的项目。我们最近与 Open Biosystems 达成了一项协议，允许西北大学的研究人员在本地完全访问先进的 RNAi 集合，这些集合可以敲除几乎所有小鼠和人类基因。这将作为核心资源通过 HTA 实验室运营。我们显然需要扩展该设施的分析能力。一组由美国国立卫生研究院 (NIH) 资助的研究人员正在开展或已经设计了各种项目，这些项目既需要高通量显微镜，又需要对所得图像数据进行复杂的形态测量分析。我们缺乏这种能力，并且该地区没有合适的共享仪器。因此，我们请求资金购买 Zeiss/Cellomics ArrayScan 成像系统，以便这些项目和其他项目能够向前推进。该系统独特地将出色的光学元件与行业领先的软件和应用程序开发支持相结合。该系统的总体好处将是推进许多由 NIH 资助的与人类健康相关的特定项目，例如癌症和与年龄相关的错误折叠蛋白质聚集体的积累。将该系统放置在开放获取的 HTA 实验室中还将为芝加哥地区、西北大学和其他地区机构的研究人员提供独特的分析工具。

DESCRIPTION (provided by applicant): Contemporary life science research has seen increasing integration of approaches that allow highly parallel analysis. The characterization of gene function, driven by completion of genome sequence, has reached a new level of importance with the advent of whole genome RNAi collections that allow large-scale abrogation of metazoan gene function. Microscopic evaluation of phenotype often represents a debilitating rate-limiting step to these approaches, and as a result high-throughput studies most often culminate with simple photometric measurements. Since much of biology rests on direct observation of cells, development of approaches allowing quantitative high-throughput analysis of cell morphology has therefore commanded considerable interest. Northwestern University's newly established High Throughput Analysis facility is a shared resource center that makes it possible for academic researchers to pursue projects that involve large-scale automation. We have recently entered into an agreement with Open Biosystems that allows researchers at Northwestern complete local access to advanced RNAi collections that allow knockdown of virtually all mouse and human genes. This will be operated as a core resource through the HTA lab. We clearly need to expand the analytical capabilities of this facility. A group of NIH-funded researchers are undertaking or have designed diverse projects that require both high- throughput microscopy and sophisticated morphometric analyses of resulting image data. We lack this capability, and no suitable shared instrument is available in the area. We are therefore requesting funds are requested for purchase of a Zeiss/Cellomics ArrayScan imaging system to allow these and other projects to move forward. This system uniquely combines outstanding optical components with industry-leading software and applications development support. The overall benefit of this system will be to advance a number of specific NIH-funded projects relevant to human health, such as cancer and age-related accumulation of misfolded protein aggregates. Placement of this system in the open access HTA Lab will also provide a unique analytical tool for Chicago-area researchers, at Northwestern and other area institutions.