PAMOC The overarching mission of the WU-DDRCC is to promote collaborative, multidisciplinary research focused on interactions between host and environment in digestive disease. The Precision Animal Models and Organoids Core (PAMOC) evolved over the previous funding period in response to changes in members' needs, and with the establishment of a new institutional gnotobiotic facility. These changes, along with guidance from our External Advisory Board, encouraged us to modify the services and objectives of this Core. Accordingly, our current objectives are to 1) assist investigators in the efficient and cost-effective development and propagation of genetically altered mouse models to elucidate the pathogenesis of digestive diseases; and 2) assist investigators in the culture of human and mouse gastrointestinal epithelial cell organoids to address cell biological questions relevant to digestive diseases and host-environment interactions. Both human and mouse gastrointestinal epithelial cells and the required media are available to DDRCC investigators for growth and differentiation of organoids. These novel models will serve as important avenues for pre-clinical studies and enable translation of basic research advances into clinical practice. KEY ACCOMPLISHMENTS since 2013 include: completed 24 nucleic acid injection projects (both conventional DNA transgenes and CRISPR/Cas9/targeting vector injections) for 7 members; 3 embryonic stem cell injection projects for 2 members; and 11 withdrawals of transgenic/knockin mice from the Mouse Bank by 9 members. Gnotobiotic services (provision of germ-free mice, rederivation to germ-free status, and gnotobiotic conventionalization) were provided to 6 members. Related to the proposed Organoid component, we have already distributed human cell lines as well as wild type and reporter mouse cell lines to 13 members. We also provided L-WRN conditioned media to 9 members. Since 2013, 22 members used the Core, resulting in 57 publications citing the WU-DDRCC.
Our SPECIFIC AIMS i nclude: (1) To assist investigators in the generation and propagation of transgenic, knockout, and knockin mice for the study of digestive diseases. This includes injections of nucleic acids, including CRISPR/Cas9 and TALEN reagents, into zygotes, assistance with rederivation of lines as specific pathogen free, and in vitro fertilization. (2) To maintain a ?Mouse Bank? containing transgenic strains of use to DDRCC investigators and to provide these mice on demand for digestive disease-relevant projects. (3) To provide banked human and mouse gastrointestinal epithelial cell lines and the culture media required for successful growth of organoids and for growth of epithelial cell monolayers. Support for monitoring cell growth and for imaging organoids will also be provided. (4) To provide assistance with the derivation of new gastrointestinal epithelial cell lines from mice and humans.
Aims 1 and 2 will continue to leverage the outstanding facilities, personnel, and expertise of the Washington University Institutional Mouse Genetics Core.
Aims 3 and 4 will benefit from infrastructure and expertise developed by Dr. Ciorba and his collaborators here at Washington University.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK052574-22
Application #
10129355
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
Budget Start
2020-12-01
Budget End
2021-11-30
Support Year
22
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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Smith, Gordon I; Commean, Paul K; Reeds, Dominic N et al. (2018) Effect of Protein Supplementation During Diet-Induced Weight Loss on Muscle Mass and Strength: A Randomized Controlled Study. Obesity (Silver Spring) 26:854-861
Rubin, Deborah C (2018) CFTR and the Regulation of Crypt Cell Proliferation. Cell Mol Gastroenterol Hepatol 5:418-419
Porter, Lane C; Franczyk, Michael P; Pietka, Terri et al. (2018) NAD+-dependent deacetylase SIRT3 in adipocytes is dispensable for maintaining normal adipose tissue mitochondrial function and whole body metabolism. Am J Physiol Endocrinol Metab 315:E520-E530
Azar, Christopher; Valentine, Mark; Trausch-Azar, Julie et al. (2018) RNA-Seq identifies genes whose proteins are transformative in the differentiation of cytotrophoblast to syncytiotrophoblast, in human primary villous and BeWo trophoblasts. Sci Rep 8:5142
Hoshi, Masato; Reginensi, Antoine; Joens, Matthew S et al. (2018) Reciprocal Spatiotemporally Controlled Apoptosis Regulates Wolffian Duct Cloaca Fusion. J Am Soc Nephrol 29:775-783
Lin, Jianguo; Zheng, Shizhong; Attie, Alan D et al. (2018) Perilipin 5 and liver fatty acid binding protein function to restore quiescence in mouse hepatic stellate cells. J Lipid Res 59:416-428
Radyk, Megan D; Burclaff, Joseph; Willet, Spencer G et al. (2018) Metaplastic Cells in the Stomach Arise, Independently of Stem Cells, via Dedifferentiation or Transdifferentiation of Chief Cells. Gastroenterology 154:839-843.e2
Funk, Steven D; Bayer, Raymond H; Malone, Andrew F et al. (2018) Pathogenicity of a Human Laminin ?2 Mutation Revealed in Models of Alport Syndrome. J Am Soc Nephrol 29:949-960
Schnadower, David; Tarr, Phillip I; Casper, T Charles et al. (2018) Lactobacillus rhamnosus GG versus Placebo for Acute Gastroenteritis in Children. N Engl J Med 379:2002-2014

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