Sterile Isolators and Associated Equipment to Establish a Gnotobiotic Facility

描述（由申请人提供）：我们的人体在我们的皮肤，肠道和整个身体中拥有庞大的微生物生态系统，实验室动物也是如此。虽然动物的这种复杂性可以模拟人类的复杂性，但有时降低这种复杂性的能力，专注于宿主和一小部分特定微生物之间的相互作用，是一种强大的研究工具。酵母菌感染是如何战胜细菌并导致免疫功能低下患者患病的？肠道微生物是否会导致多发性硬化的神经系统炎症？免疫系统如何抵御有害细菌，同时与有益微生物和谐相处？生物医学研究科学家在一系列学科寻求扩大他们的使用小鼠模型在免疫学，神经学，代谢和传染病，通过使用确定的菌群和“无菌2”gnotobiotic动物。在这些动物中，微生物可能被完全排除在外，或一个接一个地引入，因此可以精确地研究它们的个体效应和相互作用。虽然简单的微生物-细胞相互作用可以在培养物中检测，但这些体外系统目前无法取代具有复杂免疫系统的活体动物。“无菌”、无菌和确定菌群的动物只能在特殊的隔离器中饲养，呼吸过滤空气，食用无菌食物和水，只能戴着嵌在隔离器墙上的手套处理。与其他动物的任何接触，甚至是与室内空气中、手套上或台面上的微生物的接触，都会给科学带来许多未知的变量。我们寻求资金购买隔离器和相关设备，以建立一个共享用户的gnotobiotic设施在加州大学旧金山分校。该设备将使多学科医学科学家团队能够进行他们目前无法在人类受试者、培养物或常用动物中进行的研究。如果获得资助，啮齿动物隔离器将在实验动物兽医的指导下安装在UCSF实验动物资源中心（LARC）运营的“超级屏障”设施内。

DESCRIPTION (provided by applicant): 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.