The human microbiome project initiated in 2008 has led to important discoveries regarding the regulation of human disease and gene interaction with the host microbiome. At the University of California, Davis (UCD), there are currently 22 active grants, 16 pending grants and 26 investigators that require access to genetically-altered mice maintained in gnotobiotic vivarium facilities in order to model disease relationships between the host microbiome and genome. However, UCD does not currently have the animal housing infrastructure to house, maintain, or provide mice maintained under gnotobiotic conditions necessary to conduct these research activities. The NIH G20 mechanism enables institutions to upgrade animal facilities, including alterations and purchase of animal care equipment to support the conduct of biomedical and/or behavioral research. Therefore, the goal of this application is to upgrade and renovate a portion of the UCD animal care infrastructure in the Cole B vivarium and to purchase flexible film isolators, cages, and accessories to create gnotobiotic conditions enabling the importation, care and use of genetically-altered mice with defined flora for biomedical research. The proposed renovations include the allocation of three dedicated rooms to the proposed Gnotobiotic Mouse Research Center (GMRC) 1) Gnotobiotic Preparation Room 2) Gnotobiotic Rederivation Room and 3) Gnotobiotic Experimental Room. Current methods of evaluating host-microbiome interaction are centered around the use of mildly pathogenic bacteria as well as viral challenges to evaluate the effects on host mucosal immunity and metabolism. In order to perform challenges under these potential ABSL2 conditions, the gnotobiotic experimental room will require renovations, including the addition of a sink within the room, to comply with the BMBL requirements for hand washing prior to exit of an area where infectious animals are challenged. Additional requirements for this room will include the addition of a combination Class II Type A2 Biosafety cabinet / Animal Transfer station in which animals can be manipulated if needed and materials can be staged prior to entry into an experimental isolator for animal challenge experiments. In order to support the additional electrical load of the flexible film isolator equipment required for housing gnotobiotic animals, electrical renovation is needed to supply additional outlets in the gnotobiotic rederivation room and the gnotobiotic experimental room. Additional specialty equipment will also be requested as part of this project including flexible film surgical isolators to facilitate the IVF rederivation f (germ-free) axenic animals with defined genetic mutations. The renovated facility will become the campus' centralized animal care resource and service component known as the UC Davis Gnotobiotic Mouse Research Center (UCD-GMRC) with the goal of enabling the use of mutant mouse models to explore the pathobiological integration of the microbiome in health and disease.
