Overview
Our laboratory focuses on the study of host-microbe interactions and innate immunity in the nematode Caenorhabditis elegans. In recent years there has been an emerging appreciation of the complex interactions between host organisms and both pathogenic as well as beneficial microbes. Bacteria represent both a source of nutrients and a potential cause of lethal infection to the C. elegans host.  We focus on the genetic analysis of how C. elegans navigates its microbial environment and responds with evolutionarily conserved innate immune responses.

Research Summary
Innate immunity in C. elegans. We have used a genetic approach to identify genes required for immunity in C. elegans. We have identified a p38 mitogen-activated protein kinase pathway that functions downstream of a conserved module comprised of the Toll-Interleukin-1 Receptor domain protein TIR-1, MAPKKK NSY-1, and MAPKK SEK-1. The TIR-1-NSY-1-SEK-1 signaling module is orthologous to mammalian SARM-ASK1-MKK3. The C. elegans p38 MAPK pathway regulates a set of pathogen-induced effectors that include putative antimicrobial peptides and C-type lectin domain proteins. We have been using a combination of genetic and biochemical approaches to define both upstream inputs into this pathway that may mediate pathogen recognition processes, as well as downstream effector mechanisms and their transcriptional regulation. We have also been exploring links between innate immune signaling in C. elegans and potentially related physiological processes including aging and cellular responses to stress. We anticipate that the genetic dissection of innate immunity in the worm will provide insights into evolutionarily conserved mechanisms of microbial recognition and response that govern host defense in phylogenetically diverse species.

Neuroendocrine responses to pathogens. C. elegans responds to pathogenic bacteria not only with innate immune responses, but also with behavioral avoidance and aversive learning responses as shown by Bargmann and colleagues. The relatively simple and well-characterized 302 neuron nervous system of the adult hermaphrodite provides a genetically tractable system in which to investigate neuronal responses to microbial infection. We have recently demonstrated a key role for aerotaxis-dependent behavioral responses modulated by the npr-1 gene, encoding a G protein-coupled receptor, in promoting survival to pathogenic bacteria. We are currently investigating the host-microbe interactions that trigger the behavioral avoidance of C. elegans to pathogenic bacteria. We are also investigating the mechanisms by which neuroendocrine signaling can coordinate innate immunity in C. elegans.

Selected Publications
Reddy, K.C., Andersen, E.C., Kruglyak, L., Kim, D.H. (2009) A polymorphism in npr-1 is a behavioral determinant of pathogen susceptibility in C. elegans. Science 323, 382-4.

Powell, J.R., Kim, D.H., Ausubel, F.M. (2009) The G protein-coupled receptor FSHR-1 is required for the Caenorhabditis elegans innate immune response. Proc. Natl. Acad. Sci. USA 106, 2782-7.

Kim, D. (2008) Studying host-pathogen interactions and innate immunity in Caenorhabditis elegans. Disease Models and Mechanisms 1, 205-8.

Shivers,R.P., Youngman,M.J., Kim,D.H. (2008) Transcriptional responses to pathogens in C. elegans. Current Opinion in Microbiology 11, 251-256.

Troemel, E.R., Chu, S.W., Reinke, V., Lee, S.S., Ausubel, F.M., Kim, D.H. (2006)
p38 MAPK regulates immune response genes and contributes to longevity in C. elegans. PLoS Genetics 2(11) e183, 1725-1739.

Kim, D.H., Ausubel, F.M. (2005) Evolutionary perspectives on innate immunity from the study of Caenorhabditis elegans. Current Opinion in Immunology 17(1), 404-410.

Kim, D.H.*, Feinbaum, R.*, Alloing, G., Emerson, F.E., Garsin, D.A., Inoue, H., Tanaka-Hino, T., Hisamoto, N., Matsumoto, K., Tan, M.-W., Ausubel, F.M. (2002) A Conserved p38 MAP Kinase Pathway in Caenorhabditis elegans Innate Immunity. Science 297, 623-626. (*equal contributors).

See Google Scholar for Kim publications.

Intestinal infection of C. elegans with Pseudomonas aeruginosa expressing GFP, visualized under differential interference contrast microscopy (top) and fluorescence microscopy (bottom).