Histones, abundant DNA packaging molecules, have recently been shown to possess antimicrobial activity in numerous vertebrates including humans. This activity has not been demonstrated in invertebrates where innate immunity is the sole system for antimicrobial defense. This project focuses on the fundamental mechanisms, at the cellular and molecular levels, of the innate immune system of the Pacific white shrimp, Litopenaeus vannamei. More specifically, the role of histones as potential antimicrobial defense molecules in shrimp will be investigated. The goals of the project are to determine the distribution and molecular structures of histone proteins in shrimp tissues and to measure their spectrum of activity against a variety of microbes. In addition, the distribution and expression levels of histones will be examined in response to bacterial and viral infection. State-of-the-art technology in protein structure determination and tissue imaging will be used. It is expected that important new information will be obtained on the regulation and mechanisms of innate defense systems of shrimp. The broader scientific implications of the work include a greater understanding of the innate defense systems in other species, including vertebrate species, as well as an increased understanding of the multiple roles of histones in animal physiology. This project will significantly contribute to the NSF-supported Marine Genomics Initiative in South Carolina and to the education of graduate and undergraduate students in the Marine Biomedicine Program.