Developing and Improving the UAB Gnotobiotic Facility.

描述(申请人提供)：人类微生物学的一场革命正在进行，这将对健康产生深远的影响。人体中的微生物细胞(微生物区系)的数量比人体本身的细胞多一个数量级，它们的集体基因组(微生物组)中的基因数量比人类基因的数量多两个数量级。将人类及其微生物和病毒成分视为一个紧密交织在一起的超级有机体具有广泛的意义；正如一位免疫学家所描述的那样，这种思维转变“在哲学上与地球不是太阳系中心的认识没有什么不同。”使用已知微生物区系的小鼠(灵生小鼠)进行的研究为许多疾病的发病机制提供了基本的、以前无法获得的见解，包括炎症性肠病(炎症性肠病；克罗恩病和溃疡性结肠炎)和结肠癌。此外，很明显，肠道微生物区系影响能量代谢，因此 在营养、肥胖和“代谢综合征”以及继而发展成2型糖尿病、高血压和动脉粥样硬化方面具有重要的潜在作用。最近，有证据表明，微生物区系也影响哮喘等过敏性疾病的发展。为了支持19名UAB调查人员的微生物组研究进展，我们获得了1250万美元的积极外部资金和约1090万美元的未决申请，我们请求提供资金来扩大UAB GnotoBiotic设施的能力。UAB GnotoBiotic设施成立于十年前，现在需要更多的空间和设备来满足研究人员日益增长的需求，他们的研究依赖于这些重要的动物模型。为了满足研究人员的需要，我们提议翻新1,734 NSF的动物设施空间，目前用于储存、动物收容所和程序空间，以容纳最先进的半刚性隔离器，适合用于灵知菌啮齿类动物的研究；购买40个半刚性隔离器(6排)用于灵知菌动物收容所；购买专用散装高压灭菌器，购买移动液压人工升降机，以安全访问堆叠的隔离器，并购买厌氧室用于培养细菌接种剂和实验样本。此次翻修和设备采购将1)通过衍生、安置和提供灵媒啮齿动物用于UAB调查人员的研究，从而加强生物医学研究；2)更新现有的环境(暖通空调、照明)控制和监测设备，以维持动物的健康；升级应急电源，以确保隔离器的连续运行；并获取和安装高压灭菌器和半刚性、HEPA过滤隔离器，以确保宝贵的灵生动物品系的生物安全；3)促进健康的人体工程学做法，防止人体伤害和暴露在生物危害中。

DESCRIPTION (provided by applicant): A revolution in human microbiology is in progress that will have profound health implications. The microbial cells that populate the human body (the microbiota) outnumber the cells of the body itself by an order of magnitude, and the number of genes in their collective genome (the microbiome) exceeds that of human genes by two orders of magnitude. Viewing the human and its microbial and viral components as intimately intertwined as a superorganism has broad implications; as one immunologist described this shift in thinking, "is not dissimilar philosophically from the recognition that the Earth is not the centr of the solar system." Research using mice colonized with known microbiota (gnotobiotic mice) has provided fundamental, and previously unobtainable, insights into the pathogenesis of many diseases including inflammatory bowel diseases (IBD; Crohn's disease and ulcerative colitis) and colon cancer. In addition, it is clear the intestinal microbiota affect energy metabolism, thus having a substantial potential role in nutrition, obesity, and "metabolic syndrome," and in turn development of type 2 diabetes, hypertension, and atherosclerosis. Most recently, evidence has begun to appear that microbiota also affect development of hypersensitivity diseases such as asthma. In order to support the progress of microbiome studies for 19 UAB investigators with >$12.5M in active extramural funding and about $10.9M in pending applications, we request funds to expand the capacity of the UAB Gnotobiotic Facility. The UAB Gnotobiotic Facility was established a decade ago and is now in need of additional space and equipment to accommodate the increased needs of investigators whose research is dependent on these important animal models. To meet investigators needs we propose to renovate 1,734 nsf of animal facility space currently used for storage, animal housing and procedure space to accommodate state-of-the-art, semi-rigid isolators appropriate for research using gnotobiotic rodents; purchase 40 semi-rigid isolators (6 banks) for gnotobiotic animal housing; purchase a dedicated bulk autoclave, purchase a mobile, hydraulic man lift for safe access to stacked isolators, and purchase an anaerobic chamber for the culture of bacterial inocula and experimental samples. The renovation and equipment acquisition will 1) enhance biomedical research by deriving, housing, and providing the gnotobiotic rodents for use in studies by UAB investigators whose efforts are focused on understanding microbial-host interactions; 2) Maintain healthy animals by updating the existing environmental (HVAC, lighting) control and monitoring equipment; upgrading emergency power to ensure continuous isolator operation; and acquiring and installing an autoclave and semi-rigid, HEPA- filtered isolators for the biosecurity of valuable gnotobiotic mouse strains; and 3) promote healthy ergonomic practices, prevent human injuries and prevent exposure to biological hazards.