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This project will produce the initial molecular and functional characterization of antimicrobial peptides in Crassostrea virginica, thus supplying unique insight into mechanisms of disease resistance. We hypothesize that antimicrobial peptides play a significant role as protective, cytotoxic effector molecules in oysters comparable to that documented for other invertebrate and vertebrate species,. The prominent role of antimicrobial defenses in other metazoans, as well as our recent demonstration of several antimicrobial peptides in C. virginica serum, provides the rationale for this proposed study. The activity of the peptides will be tested against a panel of bacteria, yeasts and protists, including the oyster pathogens Vibrio anguillarum and Perkinsus marinus. Reduced expression of antimicrobial peptides resulting from exposure to environmental stressors, such as aquatic contaminants and hypoxia, will be measured; some of these stressors are known to exacerbate the severity and lethality of P. marinus infections. This study will help to establish a clear link between a specific manifestation of immunotoxicity and Dermo susceptibility. Antimicrobial peptides can be up-regulated in animals as diverse as insects and mammals; therefore, this phenomenon will be studied in C. virginica after administration of microbial compounds known as active immune stimulators. Knowledge gained from this project on novel mechanisms of host defense (the activity of which can be modulated by environmental conditions) may help identify specific molecules that can provide markers for developing disease resistant oysters by selective breeding or by gene transfer techniques.