Document Type

Honors Thesis

Publication Date

5-2013

Abstract

The innate immune system is highly conserved amongst all multicellular organisms. Yet a constant battle exists between host cells and pathogens due to the rapid evolution of immune system components. Functional genomics and in silico methods can be employed to elucidate the evolutionary patterns of vertebrate immunity to pathogenic fungi such as Candida albicans, an opportunistic fungal pathogen that can cause lethal candidiasis in the immunocompromised. Mammals such as humans and mice possess conserved C-type lectin receptors that recognize the C. albicans cell wall. However, these receptors have not been identified in fish. Here I describe how we identified potential zebrafish fungal recognition receptors in silico to elucidate the evolution of vertebrate immunity to fungi and to integrate cost-effective zebrafish into candidiasis research. Phylogenetic and synteny analyses identified three potential receptors with conserved motifs for fungal recognition. Cell lines secreting soluble versions of these potential receptors were generated, and the proteins were purified. These receptors are currently being analyzed for their microbial recognition characteristics through immunofluorescence microscopy. Determining the specificity of these proteins may enhance our understanding of how the innate immune system evolved in lower and higher vertebrates. Furthermore, understanding such dynamics is an initial step toward developing novel anti-fungal therapeutics for commercially valuable fish and uncovering the fundamental mechanisms of immunity to fungi.

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