Research Services Core (RSC)staff provide support to the NCATS activities in high-throughput screening, assay development, and optimization as well as follow-up and dose-response library-plating services for NCATS screening activities. The Compound Management team works in conjunction with the Automation team to provide follow-up and dose-response library-plating services for NCATS screening activities. Systems supported by the Automation team include primary screening system, Tox21 screening system, RNAi screening system, the RNAi hit picking system for assay follow ups, and multiple LabCyte Access acoustic plating systems. In the past year, we have also installed and begun to operate a LabCyte Access system to perform high throughput screens in Building 33 in a collaboration with NIAID. Together, all these systems combined provide a wide variety of automation and compound plating tasks used to enable all facets of the NCATS intramural scientific program. The primary screening system utilizes three robotic arms for plate transportation, a storage capacity of more than 3 million compound wells (approximately 2,000 1,536-well compound plates), and more than 1.5 million assay wells (approximately 1,100 1,536-well assay plates) to achieve a world-class screening productivity while maintaining the high level of data quality required by researchers. It also can run multiple assays in parallel. Center experts have developed custom software to monitor and control the system, in addition to archiving the complete process history for every screen in real time. The Tox21 screening system uses a single robotic arm for plate transportation and a storage capacity of nearly 1 million compound or assay wells (about 600 1,536-well compound or assay plates) to screen smaller scale compound libraries not present on the primary screening system and the Tox21 compound library. This platform is designed to complement the primary system, and it is easily customizable, allowing for the rapid integration of additional screening technologies. The RSC team additionally provides screening system services to intramural programs within NCATS. The Tox21 screening system contains a single robotic arm for plate transportation and a storage capacity of about 1.5 million compound wells (about 1,000 1,536-well compound plates) and more than 1.5 million assay wells (approximately 1,100 1,536-well assay plates). With a pin tool and two acoustic dispensers for compound addition, four low-volume dispensers for reagent addition, and three plate readers enabling a variety of assay detection methods, this system can rapidly screen, in triplicate, the Toxicology in the 21st Century (Tox21) library of 10,000 compounds. NCATS experts monitor and control this system with the same custom software used for the primary screening system. The RNAi screening system has two robotic arms for plate transportation with incubators for assay plate storage and plate stackers to facilitate continuous system operation. A multichannel pipettor, low volume dispensers, an aspirator for plate washing, and two different plate readers support a wide variety of detection methods for this RNAi-focused system. RSC staff also continue to support the Stem Cell Translation Laboratory (SCTL). Various team members have provided a large amount of support with a vast array of equipment including automated tissue culture systems, flow cytometers, cell sorters, and high content imagers. Special mention should be given to the automated tissue culture platform which has established itself as a core capability for all NCATS researchers now with the demand becoming so great that another system is most likely on order. These resources require a tremendous amount of expertise to operate and maintain. In the past year, RSC has begun to act as a core facility for these technologies, enabling different biology groups to increase their capabilities. Related to the high content imagers, more high content assays were run in the past year due to the increased capabilities as compared to the previous four years combined. In the past year, we added a 3rd automated tissue culture device to further increase our capacity in this space, and have configured a 4th, more automation friendly instrument from CellTrio, that is on schedule to be delivered and installed later next year. This year also finally saw our new Compound Management space setup after construction and renovations were complete. The Compound Management group moved from their previous B2 location to C1, which was a huge effort given the sheer volume of equipment, all the while ensuring that there was continued operation. In addition to the move, several critical pieces of equipment that had been ordered years prior were finally delivered and installed, including 2 Brooks Sample Store II -20C storage systems, which can be integrated with sample handling and LabCyte Echo plating systems to provide fully automated assay plate generation. This gives NCATS incredible capacity for both compound storage and flexibility to ship assay ready plates with custom plated libraries to collaborators around the world if required. The NCATS intramural program is heavily involved in COVID-19 relief efforts across the NIH. RSC is directly involved in several of these key initiatives, providing project management, scientific and technical support across several programs. Below are a list of some of the COVID-19 projects RSC has worked on: Antiviral Prevention Program (APP) laboratory standup: NCATS received a substantial amount of funding as part of the APP, with many or responsibilities related to high throughput screening, compound management (including anti-viral library design and compound acquisition), assay development and design, and data sharing. RSC was involved in all these activities, helping to fit out an entire lab worth of equipment including instrument selection, ordering, setup, and operation. This was a huge amount of work given the sheer volume of equipment, and in working closely with NCATS building services stood up an entire lab to initiate work for APP in a matter of months.