Developing and Improving the UAB Gnotobiotic Facility.

开发和改进 UAB 知生设施。

• 批准号: 8525682
• 负责人: SAMUEL Corbin CARTNER
• 金额: $ 49.63万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-26 至 2015-09-25
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8525682
• 关键词: Affect; Animal Housing; Animal Model; Animals; Asthma; Atherosclerosis; Awareness; Bacteria; Behavior; Biological; Biomedical Research; Cells; Colitis; Colon Carcinoma; Communities; Crohn' s disease; Development; Disease; Emergency Situation; Energy Metabolism; Ensure; Epithelial; Equipment; Exposure to; Extramural Activities; Funding; Genes; Genome; Germ-Free; Gnotobiotic; Goals; Health; Height; Hepatic; Housing; Human; Human Microbiome; Human Resources; Human body; Hypersensitivity; Hypertension; Immune; Immunologist; Induced Mutation; Inflammatory; Inflammatory Bowel Diseases; Injury; Intestines; Investigation; Lifting; Lighting; Maintenance; Metabolic Pathway; Metabolic syndrome; Metabolism; Microbe; Microbiology; Modeling; Monitor; Mouse Strains; Mus; Neurologic; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organism; Pathogenesis; Procedures; Proteins; Publications; Request for Applications; Research; Research Design; Research Personnel; Resources; Rodent; Role; Sampling; Science; Solar System; Technology; Thinking; Ulcerative Colitis; United States National Institutes of Health; Update; Viral; Xenobiotic Metabolism; animal facility; biosecurity; commensal microbes; computerized tools; ergonomics; hazard; improved; insight; man; medical schools; meetings; microbial; microbial host; microbiome; microorganism; neuronal cell body; novel; nutrition; operation; pathogen; prevent; reconstitution

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.

描述（由申请人提供）：人类微生物学的革命正在进行中，这将对健康产生深远的影响。在人体内繁殖的微生物细胞（微生物群）的数量超过了身体本身的细胞数量级，而它们的集体基因组（微生物组）中的基因数量超过了人类基因的两个数量级。将人类及其微生物和病毒成分视为一个紧密交织的超级有机体具有广泛的含义;正如一位免疫学家所描述的那样，这种思维转变“与认识到地球不是太阳系的中心没有什么不同。“使用已知微生物群（gnotobiotic小鼠）定植的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（IBD;克罗恩病和溃疡性结肠炎）和结肠癌。此外，很明显，肠道微生物群影响能量代谢， 在营养、肥胖和“代谢综合征”中具有实质性的潜在作用，进而发展为2型糖尿病、高血压和动脉粥样硬化。最近，有证据表明，微生物群也会影响过敏性疾病如哮喘的发展。为了支持19名UAB研究人员的微生物组研究的进展，超过1250万美元的积极校外资金和约1090万美元的待申请资金，我们要求资金扩大UAB Gnotobiotic设施的能力。UAB Gnotobiotic设施成立于十年前，现在需要额外的空间和设备，以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。为了满足研究者的需要，我们建议翻新1,734个国家科学基金的动物设施空间，目前用于储存、动物饲养和手术空间，以容纳最先进的、适合使用非生物啮齿动物进行研究的半刚性隔离器;购买40个半刚性隔离器（6个库）用于非生物动物饲养;购买一个专用的散装高压灭菌器，购买一个移动的液压升降机，以便安全地进入堆叠的隔离器，并购买一个厌氧室，用于细菌接种物和实验样品的培养。翻新和设备购置将1）通过衍生，住房和提供非生物啮齿动物用于UAB研究人员的研究来加强生物医学研究，UAB研究人员的工作重点是了解微生物-宿主相互作用; 2）通过更新现有的环境，（暖通空调、照明）控制和监测设备;升级应急电源，确保隔离器连续运行;以及获取和安装高压灭菌器和半刚性、HEPA过滤隔离器，用于有价值的无菌小鼠品系的生物安全;以及3）促进健康的人体工程学实践，防止人类受伤并防止暴露于生物危害。