Cluster B: 7 High Throughput Screening

点击翻译按钮获取中文摘要

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.