Our human bodies harbor vast ecosystems of microorganisms in our skin, gut and throughout our bodies, and laboratory animals do the same. While this complexity in animals can model the complexity in humans, there are times when the ability to reduce this complexity, to focus on the interactions between host and a small defined population of microorganisms, is a powerful research tool. How do yeast infections outcompeted bacteria and cause disease in immunocompromised patients? Do intestinal microorganisms contribute to the nervous system inflammation of Multiple Sclerosis? How does the immune system fend off harmful bacteria while living in harmony with commensal beneficial microorganisms? Biomedical research scientists in a range of disciplines seek to expand their use of mouse models in immunology, neurology, metabolism, and infectious disease though the use of defined-flora and "germ-free2" gnotobiotic animals. In these animals, microorganisms may be totally excluded, or introduced one-by-one so their individual effects and interactions can be precisely investigated. While simple microorganism-cell interactions may be examined in culture, these in vitro systems cannot presently replace live animals with their complex immune systems in operation. "Germ-free," axenic, and defined-flora animals can only be maintained in special isolators, breathing filtered air, consuming sterile food and water, handled only with gloves embedded in the isolator wall. Any contact with other animals, or even with the microorganisms in the room air or on gloves or counter tops would introduce a host of unknown variables into the science. We seek funding to purchase isolators and associated equipment to establish a shared-user gnotobiotic facility at UCSF. This equipment will allow multidisciplinary teams of medical scientists to conduct research that they currently cannot pursue in human subjects, in culture, or in commonly available animals. If funded, rodent isolators will be installd within the "super barrier" facility operated by the UCSF Laboratory Animal Resource Center (LARC) under the direction of laboratory animal veterinarians.