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允许高度平行分析的方法的日益整合。随着能够大规模去除后生动物基因功能的全基因组RNAi收集的出现，基因功能的表征已经达到了一个新的重要水平。对表型的微观评估通常代表着这些方法的一个削弱速度限制的步骤，因此，高通量研究通常以简单的光度测量达到顶峰。由于生物学在很大程度上依赖于对细胞的直接观察，因此，开发能够对细胞形态进行定量的高通量分析的方法引起了人们的极大兴趣。西北大学新成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 BiosSystems达成了一项协议，允许西北大学的研究人员完全在本地访问先进的RNAi收集，从而可以敲除几乎所有的老鼠和人类基因。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一设施的分析能力。一组由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各种项目，这些项目需要高通量显微镜和对结果图像数据进行复杂的形态测量分析。我们缺乏这种能力，该地区也没有合适的共享仪器。因此，我们请求提供资金，用于购买蔡司/细胞组学ArrayScan成像系统，以使这些项目和其他项目得以推进。该系统独一无二地将出色的光学元件与业界领先的软件和应用程序开发支持相结合。这一系统的总体好处将是推进一些由美国国立卫生研究院资助的与人类健康相关的具体项目，例如癌症和与年龄相关的错误折叠蛋白质聚集体的积累。将该系统放在开放获取的HTA实验室中，也将为芝加哥地区的研究人员、西北大学和其他地区的机构提供一个独特的分析工具。

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.