The University of Iowa High Throughput Screening Facility (UIHTS) is a high throughput platform that integrates robotics, detection systems and chemical /biologics libraries. UIHTS enables scalable screening approaches, not only to foster hit and lead generation for drug discovery and development though screening of large chemical/biologics libraries; but also to facilitate molecular probe discovery for mechanism of action (MOA) studies of chemical biology through screening of focused intellectually-designed compound collections. As a university core facility, UIHTS provides highly flexible screening services, project management, and assay/technology development for investigators across campus as well as off-campus.
UIHTS is equipped to perform high throughput screening (HTS) 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. UIHTS is also equipped to 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. HTS and HCS systems 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.
UIHTS holds two “small molecule” libraries. The Spectrum Library from MicroSource consists of 2320 structurally diverse compounds including marketed and experimental drugs as well as natural products. This array of test compounds provides a rigorous platform for assay validation and testing. The larger collection is from Chembridge, the Diverset, a collection of 50,000 small molecules representing a wide swath of chemical space, optimized to be “drug like,” considering factors such as partition coefficient and Lipinski-like rules. We are also building a UI legacy library with pure natural products and medicinal chemistry-focused compounds. In addition, we are also in the process of determining the need and feasibility of obtain a biologics library, i.e. genome-wide siRNA.
Overall, UIHTS is a laboratory core focused on scalable screening approaches for drug discovery and development and molecular probe discovery for mechanism of action (MOA) studies of chemical biology for investigators across campus and beyond.