Principal Investigator Dennis Kim
C. elegans exhibits diverse behaviors in response to bacteria provided as a nutrient source, such as feeding, reproductive egg-laying, and changes in locomotion. Remarkably, the Avery and Bargmann groups have shown that C. elegans can discriminate between nutritional, beneficial bacteria, and bacteria that represent poor nutritional sources or are pathogenic. With a relatively simple, defined nervous system of 302 neurons, C. elegans represents a tractable experimental system in which to define how the nervous system processes environmental, immune, and metabolic cues to promote protective behavioral responses.
We have shown that the aforementioned TIR-1 protein acts in a MAPK-activating module in distinct tissue-specific pathways to modulate responses to bacteria. TIR-1 acts in the intestinal cells to mediate cell autonomous innate immune responses to infection, as well as in the chemosensory nervous system to mediate serotonin-dependent aversive learning responses to infection with pathogenic bacteria (Shivers et. al., 2009). These data suggest the co-option of ancestral immune signaling pathways in the evolution of physiological responses to microbes.
In addition, we have shown that a polymorphism in the npr-1 gene, encoding a neuronally-expressed G protein-coupled receptor, is a critical determinant of C. elegans survival during infection with pathogenic bacteria. Bacteria induce NPR-1-dependent behaviors that result in enhanced avoidance of pathogenic bacteria, accounting for the role of NPR-1 in modulating pathogen resistance (Reddy et al., 2009). We continue to investigate natural variation in strains of C. elegans to define polymorphisms involved in influencing behavioral avoidance responses.
We are also investigating the genetic determinants of the human opportunistic pathogen, Pseudomonas aeruginosa, that are recognized by the C. elegans host, as well as the mechanisms that P. aeruginosa utilizes to evade host recognition.