The Research Animal Facility (RAF) is central to the research conducted at The Jackson Laboratory (JAX). JAX principal investigators currently hold 138 awards totaling over $47.9 million annually for research using mice. The oldest portion of the RAF dates from 1947, and has been modified ever since as research needs changed, mouse husbandry practices evolved and the importance of defined health status was recognized. In the past 10 years, JAX has made nearly $6 million in improvements to the RAF to accommodate these changes. Emerging trends in mammalian genetics/genomics continue to drive change in patterns of mouse use at JAX. First, new mouse models for modeling human genomic variation have been developed at JAX, and are maintained in core resource colonies supported by large center grants. Researchers use these colonies to identify loci participating in a variety of complex traits, and then maintain smaller, individual colonies to refine map positions, identify and validate candidate genes. Second, many JAX investigators are using smaller colonies of specialty mutant strains of mice to conduct functional analyses on a variety of biological and molecular processes. Third, functional assessments and potential therapeutic interventions for human disease must be verified in human tissues. Advances in immunocompromised mouse hosts pioneered at JAX enable long-term engraftment of a variety of human tissues. All of these research applications require 1) high barrier animal holding rooms where the health status of experimental mice can be consistently maintained, and 2) flexible procedure space where phenotypes can be assessed, experimental manipulations performed, and tissues collected. A cross-institutional planning committee has developed a long-range plan for the RAF to meet these and other anticipated needs. This proposal requests partial funding for the first step in this plan. JAX will commit institutional funds, expected to total over $950,000, to complete the project. As the average size of individual mouse colonies maintained in the RAF decreases, JAX can reconfigure space to provide more flexible procedure space and modify existing animal holding rooms to allow operation as high barriers. To meet this objective, we propose to: 1) upgrade rooms 2845 and 2835 in Building 20 to high barriers, by purchasing and outfitting them with positively individually ventilated (PIV) caging system and ventilated changing stations. A dedicated clean corridor accessed via an existing air shower-equipped personnel entry/exit lock will service these rooms. 2) expand procedure room space by creating and equipping three procedure rooms totaling 455 ft2. The rooms are designed to offer maximum flexibility of use to accommodate increasingly complex and specialized research procedures. Two rooms will be equipped with Baker NCB-D4 Vertical Flow Biological Safety Cabinets. One will be furnished with mobile workstations to maximize flexible configuration. The project will be overseen by John Fitzpatrick, P.E., Senior Director of Facilities Services, who will serve as Facilities Person/Project Manager.