18. GOALS FOR FELLOWSHIP TRAINING AND CAREER I intend to pursue a career in academic research, investigating the mechanisms that regulate the interactions between the vertebrate digestive tract and its microflora. I plan to use zebrafish as a host model to exploit its two principle advantages over mammalian models: the developing zebrafish gut is observable in vivo, and forward genetic analysis in the host is possible. This proposed research will reveal the effects of microorganisms on the zebrafish gut, and will identify bacterial species capable of colonizing the zebrafish gut. Iwill subsequently use genetic and molecular analyses to identify mechanisms underlying specific host responses to microbes, and those factors that control the composition and behavior of the microflora. Under this fellowship, I will gain new expertise in the biology of the vertebrate digestive tract, microbiology, gnotobiology and functional genomic techniques. These new skills, combined with my current expertise in zebrafish development and genetics, will prepare me to fulfill my career goals. 19. NAME AND DEGREEW Jeffrev I. Gordon, M.D. 20. POSITION/RANK Professor and Head I21. RMESoEuAsReCHgIuNTtEdReEvSeTSloIApRmEAeSnt; gut epithelial biology; host-microbial interactions in the mouse gut 22. DESCRIPTION (Do not exceed space provided) 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 investigatethese 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 microflorawill be revealedthrough a functional genomic comparison of gene expression in the intestines of germ-free and conventionally-raised zebrafish. Third, host responsivenessto 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. PHS416-1 (Rev.12/98) Form Page 2 BB NAME (Last,first, middle initial) IndividualNRSA Application Table of Contents ========================================Section End===========================================
| 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 |
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| 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 |
