PROJECT SUMMARY The Bioscience Screening Shared Resource (BS-SR) provides SCI members with the ability to conduct high- throughput chemical, siRNA, cDNA, and high-content screens for the purpose of drug discovery and target identification. The BS-SR incorporates instrumentation (purchased with NCRR NIH Instrumentation grants S10RR019513, S10RR026338, S10OD025004, and S10OD026899), databases, and compound and molecular libraries to allow SCI members to discover novel molecular targets and identify small molecules that modulate them. The BS-SR provides access to a fully automated confocal High-Content fluorescent microplate imager with live cell, fluidics, and phase contrast options, advanced microplate 96- and 384-well head pipetting liquid handlers, and fluorescence, luminescence, and absorbance multimode microplate readers. The BS-SR has over 130,000 small molecules for compound screens, 15,000 human cDNAs for genomic screens, and whole-genome siRNA libraries targeting the human genome (the siARRAY whole human genome siRNA library from Dharmacon targeting 21,000 human genes) and the mouse genome (Qiagen mouse whole-genome siRNA set V1 against 22,000 genes). Access to the equipment and services are provided efficiently and cost-effectively through the BS-SR. The BS-SR provides access to new technologies, such as high-throughput organoid screens and other services to meet the evolving needs of SCI members. Members of all programs use the BS-SR, with the heaviest use coming from the Cancer Biology and Cancer Stem Cells and Cancer Therapeutics programs. The BS-SR participated in nine cancer-focused publications (2 high-impact). The BS-SR will become part of the new University-led Innovative Medicine Accelerator. Some major investments have already been made (e.g., 2500 FDA-approved drugs or drugs in clinical trials library) to ensure outstanding support for SCI members in the future. The annual budget of the BS-SR is $404,790, yet the CCSG request is $104,174. Accordingly, the BS-SR leverages institutional support and seeks 26% from CCSG funds, which is anticipated to decrease once BS-SR merges with the new Innovative Medicine Accelerator High-Throughput Screening Knowledge Center. The BS-SR is focused on three major scientific aims: (1) to allow access to state-of-the-art screening technologies, (2) to provide data analysis and consultation for high-throughput screens, and (3) to provide cost- effective and expeditious screening services.