Yoder Lab: Research Interest
Stategies for identifying novel innate immune response genes
The vertebrate immune response is comprised of multiple molecular and cellular components that must interface to provide the host species with an adequate defense against pathogens. Although much information is available on how individual molecules or cells respond to infection, a complete understanding of the whole-organism response to pathogen exposure remains unresolved, due to the dynamic complexity of the immune system and its interdependent innate and adaptive functionality. The zebrafish larva provides a unique model for overcoming this obstacle as the larva successfully defends itself from pathogens while lacking a functional adaptive immune system for the first 4-6 weeks of life, making it possible to examine exclusively the innate immune response in a whole-organism context. In transcriptional profiling studies it was found that novel genes that respond to pathogen associated molecular patterns in the zebrafish larva, also respond to infection stimuli in adult zebrafish and mice, underscoring the utility of this novel innate immune model for gene discovery.
We hypothesize that the transcriptional response of zebrafish larvae to infection stimuli will reveal novel genes that mediate innate immunity in mammals. In order to test this hypothesis, we are employing a novel zebrafish larvae assay to determine the whole-organism transcriptional response to pathogen stimuli in the absence of adaptive immunity, and validating the role of functionally uncharacterized pathogen-responsive “target” genes in zebrafish, mouse and human innate immune response. The long range goal of the proposed research is to define and evaluate the role of these “target” genes during the immune response in the context of the whole organism. This and future research constitute a complementary, multi-organism paradigm for investigating, evaluating and modulating the vertebrate innate immune response.