Vertebrates have evolved within a world dominated by microorganisms, and the vertebrate microflora consequently plays important roles in gut development and physiology. However, the mechanisms that underlie these host-microbial interactions remain almost entirely unknown. The zebrafish provides new opportunities to investigate these processes using forward genetic analysis, and in vivo observation of the developing gut and its inhabitants. The goal of this proposal is to reveal the impact of microbes on zebrafish gut biology. First, zebrafish will be reared free of any microbes (germ-free or gnotobiotic zebrafish), and the morphology of germ-free and conventionally-raised zebrafish intestines will be compared. Second, the range of host processes affected by the microflora will be revealed through a functional genomic comparison of gene expression in the intestines of germ-free and conventionally-raised zebrafish. Third, host responsiveness to microbial colonization will be assayed by similarly analyzing the response of germ-free zebrafish to selected microbial species. This proposed research would provide a foundation for future analysis of the host and microbial mechanisms that regulate the rich ecosystem within the vertebrate digestive tract.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK062675-01
Application #
6552906
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Podskalny, Judith M,
Project Start
2002-12-01
Project End
2005-11-30
Budget Start
2002-12-01
Budget End
2003-11-30
Support Year
1
Fiscal Year
2002
Total Cost
$38,320
Indirect Cost
Name
Washington University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Volkman, Hannah E; Pozos, Tamara C; Zheng, John et al. (2010) Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium. Science 327:466-9
Flynn 3rd, Edward J; Trent, Chad M; Rawls, John F (2009) Ontogeny and nutritional control of adipogenesis in zebrafish (Danio rerio). J Lipid Res 50:1641-52
Rawls, John F; Mahowald, Michael A; Goodman, Andrew L et al. (2007) In vivo imaging and genetic analysis link bacterial motility and symbiosis in the zebrafish gut. Proc Natl Acad Sci U S A 104:7622-7
Rawls, John F; Mahowald, Michael A; Ley, Ruth E et al. (2006) Reciprocal gut microbiota transplants from zebrafish and mice to germ-free recipients reveal host habitat selection. Cell 127:423-33
Rawls, John F; Samuel, Buck S; Gordon, Jeffrey I (2004) Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota. Proc Natl Acad Sci U S A 101:4596-601