Sterile Isolators and Associated Equipment to Establish a Gnotobiotic Facility

描述(申请人提供)：我们的人体在我们的皮肤、肠道和全身都有巨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确定的微生物群体之间的相互作用，是一个强大的研究工具。酵母菌感染如何胜过细菌，并在免疫功能低下的患者中导致疾病？肠道微生物对多发性硬化症的神经系统炎症有贡献吗？免疫系统如何在与共生有益微生物和谐共生的同时抵御有害细菌？一系列学科的生物医学研究科学家试图通过使用确定的菌群和无菌灵知菌动物来扩大他们在免疫学、神经学、新陈代谢和传染病方面对小鼠模型的使用。在这些动物中，微生物可能被完全排除，或逐一引入，以便准确地研究它们的个体效应和相互作用。虽然可以在培养中检查简单的微生物-细胞相互作用，但这些体外系统目前还不能用它们复杂的免疫系统来取代活的动物。“无菌”、无菌、有明确菌群的动物只能保存在特殊的隔离器中，呼吸过滤后的空气，消耗无菌的食物和水，只能用嵌在隔离器壁上的手套处理。与其他动物的任何接触，甚至与房间空气、手套或台面上的微生物的接触，都会给这项科学带来一系列未知的变量。我们寻求资金购买隔离器和相关设备，以在加州大学旧金山分校建立一个共享用户灵知生菌设施。这种设备将使医学科学家的多学科团队能够进行他们目前无法在人类受试者、培养物或常见动物身上进行的研究。如果获得资金，啮齿动物隔离器将安装在由加州大学旧金山分校实验动物资源中心(LARC)在实验动物兽医指导下运营的“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.