Mechanisms of nitrogen handling, toxicity and tolerance in fishes

我的研究的总体目标是确定鱼类如何产生和排泄氨和尿素等代谢废物，以及它们如何科普这些产品的潜在毒性积累。 高毒性氨来自蛋白质的分解，必须排出或转化为毒性较小的产品，如尿素。氨在摄食后在鱼体内积累，但当通过鳃的排泄物被改变的水化学（例如> pH）或由自然（例如有机材料的分解）或人为来源（例如污水和工业废水，农业径流）产生的高水氨阻断时也会积累。在哺乳动物中，氨升高是由肝脏疾病引起的，并可能导致脑损伤或死亡。虽然氨靶向中枢神经系统（CNS），但其毒性机制尚未解决。我的长期目标是确定氨和其他代谢废物的积累如何对鱼类的生理过程产生不利影响。我的大部分工作将集中在海七鳃鳗，谁花了第一部分，他们的生活作为滤食幼虫之前，蜕变成寄生虫，饲料的血液鱼类。我以前的研究表明，喂食深刻刺激氨和尿素排泄寄生七鳃鳗，因为他们吃鲨鱼和鳟鱼的血液。在这项工作的基础上，我在未来5年的目标是：（一）使用模拟和实际饲养研究，以确定如何尿素和其他废物的耐受性和排泄七鳃鳗后ingarteriosteleost血或富含尿素的鲨鱼血，（二）确定急性氨毒性和耐受性的机制，在中枢神经系统的氨敏感的鳟鱼和氨耐受金鱼，（三）确定如何长期亚致死氨暴露影响鱼类中枢神经系统。我将使用的综合方法来完成这项研究将包括整个动物模型，培养的脑细胞，分子技术和电生理学方法。 由于七鳃鳗代表了原始的无颌鱼类，我的工作将回答脊椎动物排泄废物的机制和进化的基本问题。新的氨耐受机制也可能被确定，使一些鱼类能够承受高水平的这种神经毒素。

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.