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

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.

Agency
National Institute of Health (NIH)
Institute
Office of The Director, National Institutes of Health (OD)
Type
Animal (Mammalian and Nonmammalian) Model, and Animal and Biological Material Resource Grants (P40)
Project #
5P40OD010995-10
Application #
8474856
Study Section
Special Emphasis Panel (ZRR1-CM-5 (01))
Program Officer
Mirochnitchenko, Oleg
Project Start
2003-07-01
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
10
Fiscal Year
2013
Total Cost
$510,018
Indirect Cost
$179,558
Name
University of North Carolina Chapel Hill
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Harley, Isaac T W; Stankiewicz, Traci E; Giles, Daniel A et al. (2014) IL-17 signaling accelerates the progression of nonalcoholic fatty liver disease in mice. Hepatology 59:1830-9
Arthur, Janelle C; Gharaibeh, Raad Z; Mühlbauer, Marcus et al. (2014) Microbial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer. Nat Commun 5:4724
Ooi, Jot Hui; Waddell, Amanda; Lin, Yang-Ding et al. (2014) Dominant effects of the diet on the microbiome and the local and systemic immune response in mice. PLoS One 9:e86366
Camp, J Gray; Frank, Christopher L; Lickwar, Colin R et al. (2014) Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape. Genome Res 24:1504-16
Oh, Jason Z; Ravindran, Rajesh; Chassaing, Benoit et al. (2014) TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity 41:478-92
Lindenstrauss, Angela G; Ehrmann, Matthias A; Behr, Jürgen et al. (2014) Transcriptome analysis of Enterococcus faecalis toward its adaption to surviving in the mouse intestinal tract. Arch Microbiol 196:423-33
Shanahan, Michael T; Carroll, Ian M; Grossniklaus, Emily et al. (2014) Mouse Paneth cell antimicrobial function is independent of Nod2. Gut 63:903-10
Maharshak, Nitsan; Packey, Christopher D; Ellermann, Melissa et al. (2013) Altered enteric microbiota ecology in interleukin 10-deficient mice during development and progression of intestinal inflammation. Gut Microbes 4:316-24
Tchaptchet, Sandrine; Fan, Ting-Jia; Goeser, Laura et al. (2013) Inflammation-induced acid tolerance genes gadAB in luminal commensal Escherichia coli attenuate experimental colitis. Infect Immun 81:3662-71