Mechanisms of nitrogen excretion, toxicity and tolerance in ancient and modern fishes

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The overarching aim of my research is to determine how fishes produce and excrete nitrogenous wastes (N-wastes) such as ammonia and urea, and how they cope with potentially toxic build-ups of these products. The breakdown of excess amino acids generates neurotoxic ammonia that must either be excreted or converted to less toxic wastes such as urea. Although ammonia targets the central nervous system (CNS), its precise mechanism of toxicity is unresolved. Blood and CNS ammonia may reach toxic concentrations due to liver failure in mammals. In fishes, internal ammonia increases following feeding, and when excretion by the gill is prevented by altered water chemistry (e.g. > water pH) or elevated water ammonia arising from natural (e.g. decomposition of organic material) or anthropogenic sources (e.g. sewage effluent, agricultural run-off). I propose to determine how N-waste excretion systems in fishes are influenced by feeding and life-stage, and to identify the underlying mechanisms of ammonia toxicity and tolerance. Sea lampreys will be the model for studying excretion. My previous work demonstrated that feeding profoundly stimulated ammonia and urea excretion in parasitic lampreys as they fed on the blood of sharks and trout, making them ideal for learning more about the mechanisms and evolution of N-waste excretion strategies in vertebrates. Goldfish and trout will be used to determine how the CNS of fishes copes with build-ups of ammonia when excretion is impaired or after feeding. My objectives for the next 5 years will be to: (i) determine how ammonia and urea transport systems are altered during the lamprey life-cycle and by feeding, (ii) identify the mechanisms of acute ammonia toxicity and tolerance in the CNS of goldfish and more ammonia-sensitive trout, and (iii) ascertain how feeding and prolonged sub-lethal ammonia exposure affect the ammonia-tolerance and CNS of goldfish and trout. The integrative approach I will use will include whole animal models, cultured brain cells, molecular techniques, and electrophysiology. This research will answer fundamental questions on the mechanisms and evolution of waste excretion in vertebrates, and it may identify novel mechanisms of ammonia tolerance in fish.