John F. Rawls, PhD
Assistant Professor

Education:

BS, Emory University 1996
PhD, Washington University 2001

Molecular and genetic analysis of host-microbial interactions in the vertebrate digestive tract

The intestine harbors a large and diverse community of microorganisms, collectively known as the microbiota. The host and its microbiota form a complex relationship, the foundations of which have been forged over the course of animal evolution. Experiments using germ-free vertebrate models have shown that the gut microbiota impacts many aspects of host biology, including modulation of host nutrient metabolism, immune system development, and epithelial cell renewal. These findings indicate that the microbiota serves as a microbial 'organ', playing an integral role in host development and physiology. The characterization of factors that help establish and sustain host-microbial relationships in the digestive tract should lead to new ways of manipulating our biology to promote health, and to treat diseases such as inflammatory bowel disease and obesity. Despite the importance of the microbiota in host biology, many of the host and microbial factors that mediate these interactions are not yet understood.

We are using the zebrafish (Danio rerio) to investigate the mechanisms underlying host-microbial interactions in the vertebrate gut. The zebrafish is optically transparent from organogenesis through the onset of adulthood, facilitating in vivo real-time observations of the digestive tract and its microbial inhabitants. Furthermore, the small size of the zebrafish facilitates high-throughput genetic and chemical screens. We have developed methods for rearing germ-free zebrafish, and used those techniques to identify host responses to the gut microbiota that have been evolutionarily conserved between fish and mammals. To generate simplified experimental platforms, we have also identified individual bacterial members of the gut microbiota that elicit conserved host responses upon colonization of germ-free zebrafish. Our results indicate that different host responses are caused by distinct bacterial signals, and that these host-microbial interactions are regulated by dietary composition. Current research projects are focused on the following areas:

Microbial regulation of host nutrient metabolism: Members of the gut microbiota are able to process otherwise indigestible nutrients in the diet, leading to increased nutrient absorption and energy storage by the host. We are employing genetic methods in selected members of the gut microbiota to identify and characterize the bacterial factors that mediate this process. Molecular and biochemical approaches are also being taken to understand how the host interprets and responds to these bacterial signals.

Innate immune responses to the gut microbiota: The gut microbiota stimulates a range of innate immune responses in the host, including production of acute phase proteins, improved epithelial barrier function, and recruitment of granulocytes. We are combining genetic methods in zebrafish with genetic and biochemical analyses in bacteria, to understand the microbial signals and host signal transduction pathways that facilitate this process.

Selected Publications:
(link to all PubMed publications)

Rawls, J.F., Mahowald, M.A., Goodman, A.L., Trent, C.M., and Gordon, J.I. (2007) In vivo imaging and genetic analysis link bacterial motility and symbiosis in the zebrafish gut. Proc. Natl. Acad. Sci. U.S.A. 104(18): 7622-7627.

Rawls, J.F., Mahowald, M.A., Ley, R.E., and Gordon, J.I. (2006) Reciprocal gut microbiota transplants from zebrafish and mice to germ-free recipients reveal host habitat selection. Cell 127(2): 423-433.

Rawls, J.F., Samuel, B.S., and Gordon, J.I. (2004) Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota. Proc. Natl. Acad. Sci. U.S.A. 101(13): 4596-4601.

Rawls, J.F., Frieda, M.R., McAdow, A.R., Gross, J.P., Clayton, C.M., Heyen, C.K., and Johnson, S.L. (2003) Coupled mutagenesis screens and genetic mapping in zebrafish. Genetics 163(3): 997-1009.

Rawls, J.F., and Johnson, S.L. (2003) Temporal and molecular separation of the kit receptor tyrosine kinase's roles in melanocyte migration and survival. Dev. Biol. 262(1): 152-161.

Rawls, J.F., and Johnson, S.L. (2001) Requirements for the kit receptor tyrosine kinase during regeneration of zebrafish fin melanocytes. Development 128(11): 1943-1949.

Rawls, J.F., Mellgren, E.M., and Johnson, S.L. (2001) How the zebrafish gets its stripes. Dev. Biol. 240(2): 301-314.

Rawls, J.F., and Johnson, S.L. (2000) Zebrafish kit mutation reveals primary and secondary regulation of melanocyte development during fin stripe regeneration. Development 127(17): 3715-3724.