Integrating ionic regulation, acid-base balance and cardiorespiratory function in fish

我的研究旨在了解生理系统如何在不同的环境中促进最佳功能。总体方法是利用现代生物医学技术的力量来解决有关鱼类基本生理学的问题，这些问题越来越多地受到环境干扰。我认为有必要解决非常重要但简单的问题-动物如何感知周围环境，以及这种感官信息如何转化为适应性生理反应？短期目标建立在目前的研究基础上，集中在两个领域：1）化学感受和随后的心肺反应机制和2）离子和酸碱调节机制。联系这些领域的创新性新主题是稳态的代谢成本。1. * 化学感受，即生物体感知其外部或内部环境化学成分变化的能力，对可能经历环境条件大的空间和时间波动的鱼类特别重要。我的实验室主要集中在让鱼类感知周围氧气和二氧化碳水平变化的机制，以及由此引发的下游呼吸和心脏反射。最终，正是这些反射性心肺反应的生理益处（例如，当氧气水平下降时，呼吸频率增加）使鱼类能够在不稳定的环境中生存。目前的研究计划将解决与斑马鱼化学感受器，神经上皮细胞（NEC）功能相关的问题。实验设计为i）提供第一个明确的证据，即NEC有助于体内心肺反射，ii）确定涉及哪些神经递质，iii）研究化学感受器从皮肤过渡到鳃时化学感受的发展，以及iv）评估化学感受的代谢成本。2.离子（盐）和酸碱（pH）调节机制 * 淡水鱼必须不断利用能量从稀释的水中吸收盐，以补充因扩散而损失的盐。拟议的研究将解决斑马鱼通过幼虫皮肤和成虫鳃上的专门细胞（离子细胞）吸收盐的机制。具体项目将包括比较幼虫和成虫之间的离子细胞结构和功能，阐明盐吸收和细胞pH调节之间的关系，并确定盐运输的能量成本。预计拟议的研究将解决鱼类化学感觉和离子调节生理学中最重要的四个问题，同时为明天的研究领导者提供肥沃的培训基地。

My research seeks to understand how physiological systems promote optimal function in diverse environments. The overarching approach is to harness the power of modern biomedical techniques to address questions about the fundamental physiology of fish that, increasingly, are experiencing environmental perturbation. I see a need to address profoundly important but simple questions – how do animals sense their surroundings and how is this sensory information transformed into adaptive physiological responses? The short-term objectives build on current research and are centred on two areas; 1) mechanisms of chemoreception and ensuing cardiorespiratory responses and 2) mechanisms of ionic and acid-base regulation. The innovative new theme linking these areas is the metabolic cost of homeostasis.*******1. Mechanisms of chemoreception and ensuing cardiorespiratory responses****Chemoreception, the capacity of an organism to perceive changes in the chemical composition of its external or internal environment, is particularly important in fish that may experience large spatial and temporal fluctuations in environmental conditions. My laboratory has focused largely on the mechanisms allowing fish to sense changes in ambient oxygen and carbon dioxide levels and the downstream breathing and cardiac reflexes that are triggered. Ultimately, it is the physiological benefit of these reflex cardiorespiratory responses (e.g. increased breathing rates when oxygen levels fall) that enable fish to survive their labile environments. The current research proposal will address issues related to the functioning of the zebrafish chemoreceptor, the neuroepithelial cell (NEC). Experiments are designed to i) provide the first unequivocal evidence that NECs contribute to cardiorespiratory reflexes in vivo, ii) establish which neurotransmitters are involved, iii) investigate the development of chemoreception as chemoreceptors transition from the skin to the gill, and iv) assess the metabolic costs of chemoreception.*******2. Mechanisms of ionic (salt) and acid-base (pH) regulation****Freshwater fish must continually utilize energy to absorb salts from the dilute water to replenish those lost by diffusion. The proposed research will address the mechanisms whereby zebrafish absorb salts across specialized cells (ionocytes) on the skin of larvae and the gill of adults. Specific projects will include comparing ionocyte structure and function between larvae and adults, elucidating the relationships between salt uptake and cellular pH regulation, and determining the energetic costs of salt transport.*******It is anticipated that the proposed research will address four of the most important questions in fish chemosensory and ionoregulatory physiology while providing a fertile training ground for the research leaders of tomorrow.******