Grant: Discovery Grants Program - Individual

The overall goal of my research is to determine how fishes produce and excrete metabolic wastes such as ammonia and urea, and how they cope with potentially toxic build-ups of these products.  Highly toxic ammonia arises from the breakdown of protein, and must be excreted or converted to less toxic products such as urea. Ammonia accumulates in fishes following feeding, but also when excretion via the gill is blocked by altered water chemistry (e.g. > pH) or elevated water ammonia arising from natural (e.g. decomposition of organic material) or anthropogenic sources (e.g. sewage and industrial effluent, agricultural run-off). In mammals, elevated ammonia results from liver disease, and can cause brain damage or death. Although ammonia targets the central nervous system (CNS), its mechanism of toxicity is unresolved. My long-term goal is to determine how build-ups of ammonia and other metabolic wastes adversely affect physiological processes in fishes. Much of my work will focus upon sea lampreys, who spend the first part of their life as filter-feeding larvae before metamorphosing into parasites that feed on the blood of fishes. My previous research demonstrated that feeding profoundly stimulated ammonia and urea excretion in parasitic lampreys as they fed on the blood of sharks and trout. Building upon this work, my OBJECTIVES for the next 5 years are to:(i) Use simulated and actual feeding studies to determine how urea and other wastes are tolerated and excreted by lampreys after ingesting teleost blood or urea-rich shark blood, (ii) Identify the mechanisms of acute ammonia toxicity and tolerance in the CNS of ammonia-sensitive trout and ammonia-tolerant goldfish, and(iii) Determine how prolonged sub-lethal ammonia exposure affects the fish CNS. The integrative approach I will use to complete this research will include whole animal models, cultured brain cells, molecular techniques, and electrophysiological methods.  Since lampreys represent the original jawless fishes, my work will answer fundamental questions on the mechanisms and evolution of waste excretion in vertebrates. Novel mechanisms of ammonia tolerance may also be identified that allow some fishes to withstand high levels of this neurotoxin.