The Broad Institute performs high-throughput large scale biology with academic collaborators from across the country, investigating a wide variety of biological systems. In this proposal the Broad Institute core small molecule screening group is requesting funding for an automated tissue culture system to enhance our large scale biology capabilities. The instrument would be managed and maintained by the Chemical Biology platform screening group. The screening group is a team of professional scientists that has extensive industrial experience and expertise in developing and executing high-throughput cell-based assays for small molecule probe discovery. Large scale tissue culture is already performed by this team to support more than 30 MLPCN and Broad screening projects per year. Cell supply can become a limiting factor in terms of the quality and quantity of cells required. Automated tissue culture would expand our capabilities to support more projects, increase our screening throughput, improve assay quality, and free up scientists to carry out more research. The automated tissue culture platform, CompacT SelecT, grows and maintains cells from multiple cell lines in T-flasks and delivers them into microtitre plates. It is designed to generate assay-ready plates on demand for cell based screening and assay development. A CompacT SelecT would enable unattended operation, up to 24 hours a day, 7 days a week to maintain 130 T-175 tissue culture flasks and deliver 210 384 assay ready plates per day with a 3- fold reduction in manpower. The rate of progress of the large scale biology projects described in this proposal are limited by the researchers ability to scale-up cell culture, propagate multiple cell lines and maintain cell quality. We are in a unique position to offer access to this high throughput cell culture capability to many members of the scientific community. This proposal describes five projects currently funded by the NIH that would greatly benefit from the increased scale, and cell quality automated tissue culture provides. These projects are of significant interest to the biomedical research community, focusing on disease areas in metabolism, cellular differentiation, cancer, and functional regulation. Beyond these projects, the screening group has established various pathways for outreach, forming collaborations, and providing industrial-scale HTS capabilities to academic groups, including numerous NIH-funded investigators. The Broad Institute is a Comprehensive Screening Center in the NIH Molecular Libraries Probe Production Center Network (MLPCN). Automated cell culture would enable us to support many more projects without increasing our headcount.