Cluster B: 7 High Throughput Screening

UI高通量筛查核心(HTS)是一个新的霍尔登综合癌症中心(HCCC) 共享研究资源，提供集成机器人、检测系统、 化学/生物药物库、数据管理和专业知识。HTS为HCCC成员提供可扩展的 治疗学的早期、临床前开发，包括小分子治疗学、抗体、siRNA、 反义寡核苷酸和其他生物制品，包括患者衍生的细胞疗法。它还支持HIGH 为探索癌症生物学的研究进行吞吐量筛查。 自动化、小型化和并行的高通量方法促进了药物的成功和领先 通过筛选系统的、无偏见的大型化学/生物制品文库来发现和开发。 这些策略也促进了化学作用机理(MOA)研究的分子探针发现 通过筛选有重点的、经过智力设计的化合物集合来进行生物学研究。此外，这些高- 吞吐量方法有助于对细胞的询问，特别是那些来自患者的细胞。 HTS是由包括HCCC和NIH S10共享的大学赞助商于2012年建立的 仪器设备赠款资金。HTS配备了在96、384和1536年中执行高通量筛选的能力 良好的格式，带有平板阅读器检测(Perkin-Elmer enVision)，使用吸光度、荧光和 发光，包括先进的FRET和BRET技术。HTS还可以进行高含量筛选 (Perkin-Elmer opetta共焦成像系统)检测和量化表型变化，即细胞 分化、细胞迁移、突起生长和靶标运输；或通过靶标的荧光强度 蛋白质表达、转录因子或信号通路分析。HTS中提供的系统包括 与机器人集成，用于平板处理和化验执行，适用于小型或大型化合物 图书馆的屏幕具有“轻松”的自动化水平。HTS目前拥有五个“小分子”文库 含有大约140,000种化合物。此外，HTS正在确定需要和 获得生物制品文库的可行性，即全基因组siRNA、抗体和不同的细胞系。 总体而言，HTS是一个共享的研究资源，专注于可扩展的药物发现和筛选方法 开发和发现分子探针，用于癌症研究人员的作用机制研究 校园和更远的地方。

The UI High Throughput Screening Core (HTS) is a new Holden Comprehensive Cancer Center (HCCC) shared research resource that provides a high-throughput platform integrating robotics, detection systems, chemical /biologics libraries, data management, and expertise. HTS provides HCCC members with scalable early, pre-clinical development of therapeutics, including small molecule therapeutics, antibodies, siRNAs, antisense oligonucleotides and other biologics including patient-derived cell therapeutics. It also supports high throughput screening for studies exploring the biology of cancer. The automatic, miniaturized and parallel high-throughput approaches foster hit and lead generation for drug discovery and development through screening of systematic, unbiased large chemical/biologics libraries. These strategies also facilitate molecular probe discovery for mechanism-of-action (MOA) studies of chemical biology through screening of focused intellectually designed compound collections. In addition, these high- throughput approaches aid the interrogation of cells, especially those derived from patients. The HTS was established in 2012 by university sponsors including the HCCC and an NIH S10 Shared Instrumentation grant funding. HTS is equipped to perform high-throughput screening in 96-, 384- and 1536- well formats, with plate reader detection (Perkin-Elmer EnVision) using absorbance, fluorescence and luminescence, including advanced FRET and BRET techniques. HTS can also perform high content screening (HCS, Perkin-Elmer Operetta Confocal Imaging System) to detect and quantify phenotypic changes, i.e. cell differentiation, cell migration, neurite outgrowth, and target trafficking; or by fluorescence intensities for target protein expression, transcription factor or signaling pathway analysis. Systems available in the HTS are integrated with robotics for plate handling and assay execution, suitable for small- or large-scale compound library screens with “walk-away” levels of automation. HTS currently holds five “small molecule” libraries containing approximately 140,000 compounds. In addition, HTS is in the process of determining the need and feasibility of obtaining a biologics library, i.e. genome-wide siRNA, antibodies, and diverse cell lines. Overall, HTS is a shared research resource focused on scalable screening approaches for drug discovery and development, and molecular probe discovery for mechanism-of-action studies for cancer investigators across campus and beyond.