Transport and Metabolism in Fish

在一个拥有世界上最长的海岸线、拥有世界七分之一淡水的国家，以及一个渔业和渔业每年贡献超过170亿美元(体育渔业~100亿美元，商业渔业~60亿美元，水产养殖~10亿美元)的经济体，了解鱼类的基本生理和保护自然水域健康的重要性怎么强调都不为过。本申请开辟了一个长期研究计划的新领域，该计划旨在了解鱼类中营养物质、废物、离子、酸碱当量和呼吸气体的运输和代谢机制，以及这些过程是如何被环境条件和系统发育所改变的。这一基础研究项目是水生毒理学、水产养殖和环境管理的并行应用项目的基础。同时从分子、细胞、器官系统、整个动物和行为水平分析了发病机制。对物种(鲑鱼、剑鱼、鲨鱼、八角鳗、斑马鱼等)和应激源(氨、O2、二氧化碳、盐度、运动、摄食)采用比较方法。这四个主要领域是：(I)氨和尿素代谢的生理学；(Ii)“渗透呼吸折衷”，即离子/水与鳃上的O2交换之间的功能平衡；(Iii)摄食生理学；(Iv)溶解有机物(DOM，一种丰富、普遍但知之甚少的天然水体成分)在调节鳃生理学中的重要性。特别的项目集中在NH3作为一种呼吸气体在呼吸调节中的功能，它与O2和CO2的相互作用，在鳃和肾脏中氨转运Rh蛋白的基因表达的控制，以及它们在离子、酸碱状态和氮废物的动态平衡调节中的作用。在N-限制鲨鱼身上研究了N-清除机制。不同类型的渗透呼吸危害，跨细胞途径和细胞旁途径的贡献，以及它们的细胞/分子基础与盐度、栖息地和不同物种的行为有关。探讨了喂养生理学的多个方面，包括酸碱信号的重要性，与食物摄入相关的运输途径的上调，以及肠道本身的新陈代谢。量化了喂养的氧气成本及其与低氧和运动表现的相互作用。通过与化学家的合作，研究了不同类型DOM分子的物理化学及其对鳃离子调节功能的支持作用之间的关系。特别强调了DOM分子中金属结合部分的作用(S)，与DOM暴露相关的鳃结构变化，以及鱼类对自然生态系统的适应。总体而言，该项目将培训3名博士后研究员、5名博士和15名本科生在综合鱼类生理学的创新方面。

In a country with the longest coastline in the world, with 1/7 of the world's freshwater, & an economy where fish and fisheries contribute over $17B annually (sportfishing ~ $10B, commercial fishing ~ $6B, aquaculture ~ $1B), the importance of understanding the basic physiology of fish & protecting the health of natural waters cannot be overstated. The present application opens new frontiers in a long term research program aimed at understanding the mechanisms involved in the transport & metabolism of nutrients, wastes, ions, acid-base equivalents, & respiratory gases in fish, & how these processes are modified by environmental conditions & phylogeny. This basic research program underpins a parallel applied program in aquatic toxicology, aquaculture, & environmental management. Mechanisms are analyzed at molecular, cellular, organ system, whole animal, & behavioral levels simultaneously. A comparative approach is used with respect to species (trout, killifish, sharks, hagfish, zebrafish etc.) & stressors (ammonia, O2, CO2, salinity, exercise, feeding). The four main areas are: (i) the physiology of ammonia & urea metabolism; (ii) the “osmorespiratory compromise” which is the functional tradeoff between ion/water vs O2 exchange at the gills; (iii) the physiology of feeding; (iv) the importance of dissolved organic matter (DOM, an abundant, ubiquitous but poorly understood component of all natural waters) in regulating gill physiology. Particular projects focus on the functions of NH3 as a respiratory gas in the regulation of breathing, its interactions with O2 & CO2, the control of gene expression of ammonia-transporting Rh proteins in the gills & kidney, & their roles in the homeostatic regulation of ions, acid-base status, & N-wastes. The mechanisms of N-scavenging are examined in N-limited sharks. The different types of osmorespiratory compromise, the contributions of transcellular vs paracellular pathways, & their cellular/molecular bases are investigated in relation to salinity, habitat, & behaviour of different species. Multiple aspects of feeding physiology are explored, including the importance of acid-base signals, the upregulation of transport pathways associated with food ingestion, & the metabolism of the gut itself. The O2 costs of feeding & their interactions with hypoxia & exercise performance are quantified. Through collaboration with a chemist, the relationships between the physical chemistry of different types of DOM molecules & their supportive actions on gill ionoregulatory function are examined. Particular emphasis is placed on the role(s) of metal-binding moieties in DOM molecules, on structural changes in gills associated with DOM exposures, & on the adaptation of fish to native DOMs. Overall, this program will train 3 postdoctoral fellows, 5 PhDs, & 15 undergrads in innovative aspects of integrative fish physiology.