National Gnotobiotic Rodent Resource Center

国家知生啮齿动物资源中心

基本信息

批准号：
7925576
负责人：
Ryan B Sartor
金额：
$ 53.41万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-07-30 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7925576
关键词：
1-Phosphatidylinositol 3-Kinase Acetylmuramyl-Alanyl-Isoglutamine Adjuvant Administrative Supplement Advisory Committees Aerobic Bacteria Affect Affinity Age Alabama Alcoholic Liver Diseases American Anaerobic Bacteria Animal Technicians Animals Antibiotic Therapy Antigens Applications Grants Arthritis Asthma Atherosclerosis Autopsy Back Bacteria Bacterial Genes Bacteroides Binding Biological Assay Biological Models Biology Biotechnology Blood Vessels Breeding Budgets CD14 Antigen Cell Line Cells Censuses Charge Choline Chronic Chronic Disease Colitis Colon Carcinoma Communities Complex Core Facility Country Crohn&apos s disease Cryopreservation Custom Cystic Fibrosis DNA Sequencing Facility Data Defensins Degenerative Disorder Derivation procedure Detection Development Diabetes Mellitus Differentiation and Growth Direct Costs Disease Dissection Doctor of Medicine Doctor of Philosophy Embryo Embryo Transfer Endotoxins Engineering Ensure Enteral Enterobacteriaceae Enterococcus faecalis Environmental Risk Factor Epithelial Epithelial Cells Equilibrium Equipment Escherichia Escherichia coli Europe Evaluation Exhibits Faculty Feces Film Funding Gene Expression Gene Mutation Genes Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetically Engineered Mouse Genital system Genomics Germ-Free Glycoproteins Gnotobiotic Goals Grant Growth and Development function HIV Harvest Health Helicobacter hepaticus Hepatic Histopathology Housing Human Human Resources Hypoxia Immune Immune Tolerance Immune response Immunization Immunologics Immunology Inbred NOD Mice Incidence Individual Infection Infection prevention Inflammation Inflammatory Inflammatory Response Inflammatory disease of the intestine Institutes Institution Interleukin-10 International Intestines Invaded Investigation Ions Joints Knock-out Laboratories Laboratory Animal Medicine Laboratory Animals Lactobacillus Lactobacillus plantarum Lead Leadership Life Link Lipopolysaccharides Liver Liver diseases Maintenance Mammalian Oviducts Mediating Medicine Mesenchymal Metabolic Methods Microbiology Modeling Molds Molecular Mouse Models of Human Cancer Consortium Mouse Strains Mucins Mucous body substance Mus Mutant Strains Mice Mutate Mutation NF-kappa B National Center for Research Resources National Institute of Diabetes and Digestive and Kidney Diseases Nature Neoplasms North Carolina Obesity Oral Organ Organism Pancreas Parasites Pathogenesis Pathologist Patients Pattern recognition receptor Pennsylvania Performance Periodontal Diseases Phagocytosis Phenotype Phosphorylation Physiological Physiological Processes Physiology Pilot Projects Postdoctoral Fellow Principal Investigator Probiotics Process Production Protein Isoforms Proteins Proteomics Protozoa Publishing Quality Control Rat Strains Rattus Recombinant Proteins Recombinants Recording of previous events Regulation Research Research Personnel Research Support Resistance Resources Response Elements Retroviridae Rodent Role SECTM1 gene Sclerosing Cholangitis Series Services Sexually Transmitted Agents Shipping Ships Signal Transduction Signaling Molecule Skin Societies Specialist Specific Pathogen Frees Specificity Sprague-Dawley Rats Sterility Stimulus Supervision Surface Surveillance Program T-Cell Activation T-Lymphocyte Techniques Technology Texas Therapeutic Tight Junctions Time Tissue Banking Tissue Banks Tissues Toxin Training Transgenic Mice Transgenic Organisms Transplantation Travel United States United States Department of Veterans Affairs United States National Institutes of Health Universities Vasectomy Veterinary Medicine Viral Virginia Virulence Virus Washington Wisconsin Work Writing Yeasts Zebrafish antimicrobial peptide bacterial vector base biological adaptation to stress body system college commensal microbes comparative cost cytokine design dietary supplements disease phenotype enteric pathogen experience flexibility gastrointestinal germ free condition immune function improved in vivo innovation interest investigator training killings macrophage medical schools member metabolomics microbial microbial host microbiome microorganism interaction mouse model multidisciplinary neoplastic non-alcoholic novel novel strategies operation pathogen prebiotics prevent professor programs public health relevance repaired respiratory response sex sperm cell success transmission process

项目摘要

DESCRIPTION (provided by applicant): Environmental factors modify genetic susceptibility to many chronic diseases. Commensal microbiota profoundly influence physiologic responses in a number of organs and heavily contribute to inflammatory, neoplastic and possibly degenerative diseases. The NGRRC provides a resource for local, regional, national and international multidisciplinary investigators to explore the hypothesis that commensal bacteria fundamentally Influence normal physiologic processes in normal hosts and pathogenic inflammatory and neoplastic responses in genetically susceptible hosts. This unit provides a resource for broadly based investigators to examine physiologic and pathophysiologic differences in germ-free (sterile) vs. gnotobiotic (known life) vs. specific pathogen-free rodents of different genetic backgrounds, and to define the physiologic and pathophysiologic relevance of bacterial genes. The microbiota can be precisely manipulated by colonizing germ-free rodents with single or multiple commensal or pathogenic bacterial or fungal species, using isogenic wild type or genetically engineered bacterial strains. Specific aims: 1. Provide germ-free or selectively colonized wild type and mutant mice and rats or their tissues and cells to NIH-funded investigators. 2. Develop innovative techniques to efficiently derive germ-free breeding colonies of new strains of mice and rats for requesting investigators and for the molecular detection and identification of contaminating bacteria. 3. Support pilot studies for investigators with novel hypotheses to generate preliminary data for NIH grant applications. We provide a unique and essential resource for a large, diverse group of NIH-funded investigators to study the physiologic and pathophysiologic consequences of colonization by commensal bacteria, with particular emphasis on gene/environmental interactions in genetically altered mice (transgenic, knockout or spontaneously mutated) with altered physiology and disease phenotypes. In our initial 4 years of funding, the NGRRC has provided 4621 gnotobiotic mice and rats to 61 investigators in 35 institutions. 39 funded and 11 submitted grants by 32 investigators depend on gnotobiotic animals from the NGRRC. Unique features of our facility are 1) interaction with the UNC Mutant Mouse Regional Resource Center (MMRRC), 2) the experience of the applicant team, 3) innovation in embryo transfer and cryopreservation, 4) The option for onsite tissue collection by external investigators, 5) highly trained technical staff to collect tissues or isolate cells for requesting investigators. PUBLIC HEALTH RELEVANCE (provided by applicant): The NGRRC provides a local, regional, national and international resource for NIH-funded investigators to explore the role of commensal bacteria on normal physiologic and pathophysiologic processes in wild type and genetically engineered rodents and trains investigators and staff in other facilities in gnotobiotic technology. The research component of this application explores novel ways of deriving gnotobiotic mice and using molecular techniques to detect and identify contaminating organisms. In addition, it permits investigators to obtain preliminary data to submit competitive grant applications. In the past funding cycle these preliminary data and access to our facility resulted in 6 new funded grants.

描述（由申请人提供）：环境因素会改变对许多慢性疾病的遗传易感性。共生微生物群深刻影响许多器官的生理反应，并在很大程度上导致炎症、肿瘤和可能的退行性疾病。 NGRRC 为地方、区域、国家和国际多学科研究人员提供了资源，以探索共生细菌从根本上影响正常宿主的正常生理过程以及遗传易感宿主的致病性炎症和肿瘤反应的假设。该单元为广泛的研究人员提供了资源，以检查无菌（无菌）与无菌（已知生命）与不同遗传背景的特定无病原体啮齿动物之间的生理和病理生理差异，并定义生理和病理生理相关性细菌基因。通过使用同基因野生型或基因工程细菌菌株，用单个或多个共生或致病细菌或真菌物种定殖无菌啮齿动物，可以精确地操纵微生物群。具体目标： 1. 向 NIH 资助的研究人员提供无菌或选择性定植的野生型和突变型小鼠和大鼠或其组织和细胞。 2. 开发创新技术，有效地获得新小鼠和大鼠品系的无菌繁殖群体，以供研究人员以及污染细菌的分子检测和鉴定。 3. 支持研究人员进行新假设的试点研究，为 NIH 拨款申请生成初步数据。我们为 NIH 资助的大型、多样化的研究人员提供了独特且重要的资源，以研究共生细菌定植的生理和病理生理后果，特别强调基因改变小鼠（转基因、敲除或自发突变）的基因/环境相互作用）具有改变的生理学和疾病表型。在最初 4 年的资助中，NGRRC 已向 35 个机构的 61 名研究人员提供了 4621 只无菌小鼠和大鼠。 32 名研究人员有 39 项资助和 11 项提交资助依赖于 NGRRC 的限生动物。我们设施的独特之处在于 1) 与北卡罗来纳大学突变小鼠区域资源中心 (MMRRC) 的互动，2) 申请团队的经验，3) 胚胎移植和冷冻保存方面的创新，4) 外部研究人员可以进行现场组织采集，5）训练有素的技术人员为有要求的研究者收集组织或分离细胞。公共健康相关性（由申请人提供）：NGRRC 为 NIH 资助的研究人员提供地方、区域、国家和国际资源，以探索共生细菌对野生型和基因工程啮齿动物正常生理和病理生理过程的作用，并培训研究人员和其他生殖技术设施的工作人员。该应用程序的研究部分探索了培育无菌小鼠并使用分子技术检测和识别污染生物体的新方法。此外，它还允许研究人员获得初步数据以提交竞争性资助申请。在过去的资助周期中，这些初步数据和对我们设施的访问导致了 6 项新的资助。