Project Summary P01 Grant Title: Greater Caribbean Center for Ciguatera Research Project 3 title: Translation: Human mechanisms of genotoxicity and cellular metabolism Project 3 inter-relates with Projects 1 and 2 by providing details of human cellular response following exposure to the isolated Ciguatoxins. Discoveries herein will be shared with the Project leads and Administrative core to provide a comprehensive information flow to the Community Engagement Core for regular content distribution and awareness to the effected stakeholders. Guided by the modeling of Project 1 to understand Gambierdiscus population dynamics in the region, Project 2 will yield the isolated Gambierdiscus-derived toxins, including details on bioaccumulation throughout the foodweb. The Project 3 team will work closely with the Project 2 lead (Alison Robertson) to clarify and discover genotoxicity mechanisms of CTX exposure, how exposure varies (acute vs chronic) and if exposure impacts secondary exposure to other environmental agents. Finally, Project 3 will evaluate detailed mechanisms of subcellular crosstalk that may reveal novel biomarkers associated with exposure. This will be accomplished, as will be described in detail throughout the Research Plan, using novel, state-of-the-art technologies developed by and optimized in the Sobol lab, including a new genotoxin screening platform (CometChip) that provides greater than ~10,000-fold greater capacity and sensitivity than previous genotoxicity analytical approaches, novel high-resolution cellular imaging tools for Ca2+ signaling, metabolite (ATP, NAD+) quantification, cell death mechanisms, mitochondrial function and genomic signaling response.