Ciguatera fish poisoning (CFP) is the most common form of phycotoxin-borne seafood illness across the globe, affecting tens of thousands of people annually. CFP is caused by the consumption of seafood (primarily reef fish) contaminated with ciguatoxins. Gambiertoxins, precursors of ciguatoxins produced by the (sub)tropical benthic dinoflagellate genus Gambierdiscus, enter reef food webs when herbivores and detritivores consume Gambierdiscus directly or indirectly by grazing on macroalgae. These precursor molecules are transferred to higher trophic levels by bioaccumulation, bioconversion and biomagnification until they reach predatory finfish species that are targeted in many commercial and recreational fisheries. When people subsequently consume the contaminated fish, they are exposed to the toxins, thereby experiencing CFP. Historically, CFP outbreaks have been linked with warm water temperatures and coral reef impacts, both of which are expected to increase in the setting of climate change. Consequently, CFP is predicted to increase on geographic and temporal scales. For example, although CFP is endemic to the Caribbean, the Florida Keys, and South Florida, CFP appears to be expanding northwards into the Gulf of Mexico, highlighted by the recent identification of toxic fish in the Flower Garden Marine Sanctuary off of the Texas/Louisiana coast. Ciguatoxin is a novel type of voltage-gated ion channel toxin. In nerve tissues, ciguatoxin causes a tetrodotoxin-sensitive increase in sodium ion permeability and depolarization of the resting membrane. Depending on the magnitude of the depolarization, the consequence can be an increase in excitability of the neuronal membrane or a depolarizing type of conduction block at high concentrations. The onset of CFP is typically characterized by gastrointestinal and neurological symptoms and signs typically persist for days to weeks, with vomiting, diarrhea, nausea, abdominal pain, dysesthesia, pruritus, myalgia being common. Severe cases of ciguatera may involve hypotension and bradycardia, but fatalities are rare. Occasionally, neurological signs may persist for several months. Remarkably, the diagnosis of ciguatera is still largely dependent on the astuteness of the clinician. In the absence of a confirmatory laboratory test, a sizable proportion of cases still go undiagnosed and unreported. The enigmatic nature of CFP events, coupled with a lack of sustained scientific research on the environmental and physiological factors that contribute to outbreaks, has hindered progress in the development of management strategies to protect people against exposure to ciguatoxins. The purpose of this project, therefore, is to establish a Greater Caribbean Center for Ciguatera Research to 1) examine the role climate change may play in the geographic and temporal expansion of CFP into more temperate latitudes; 2) obtain a better understanding of the toxic metabolites produced by certain Gambierdiscus strains, and the subsequent transfer and biotransformation of these compounds into coastal/reef food webs; and 3) study the genotoxicity and impacts on cellular metabolism caused by these toxins upon exposure.