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越来越多的方法集成，允许高度并行分析。基因功能的表征，由基因组序列完成驱动，随着全基因组RNAi集合的出现，允许大规模废除后生动物基因功能，基因功能的表征已经达到了一个新的重要水平。显微镜下的表型评估通常代表了这些方法的削弱率限制步骤，因此高通量研究通常以简单的光度测量告终。由于生物学的大部分工作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从事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当地完全访问先进的RNAi集合，这些集合可以敲低几乎所有的小鼠和人类基因。这将通过HTA实验室作为核心资源进行操作。我们显然需要扩大这个设施的分析能力。一组美国国立卫生研究院资助的研究人员正在进行或已经设计了不同的项目，这些项目既需要高通量显微镜，也需要对产生的图像数据进行复杂的形态计量学分析。我们缺乏这种能力，在该地区也没有合适的共享仪器。因此，我们请求资金用于购买蔡司/Cellomics ArrayScan成像系统，以使这些和其他项目向前推进。该系统独特地将优秀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。该系统的总体效益将是推进一些由nih资助的与人类健康相关的特定项目，如癌症和与年龄相关的错误折叠蛋白质聚集体积累。在开放获取的HTA实验室中放置该系统还将为芝加哥地区的研究人员、西北大学和其他地区机构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.