Developing and Improving the UAB Gnotobiotic Facility.

描述（由申请人提供）：人类微生物学的一场革命正在进行中，这将对健康产生深远的影响。构成人体的微生物细胞（微生物群）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（微生物群）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超级有机体，有着广泛的意义；正如一位免疫学家对这种思维转变的描述，“从哲学上讲，这与认识到地球不是太阳系的中心并没有什么不同。”使用已知微生物群定植的小鼠（非生物小鼠）进行的研究为许多疾病的发病机制提供了基础的，以前无法获得的见解，包括炎症性肠病（IBD；克罗恩病和溃疡性结肠炎）和结肠癌。此外，肠道菌群明显影响能量代谢，因此

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.