Integrative control of cardiorespiratory energetics during stress

在水生动物中，维持能量平衡和心肺功能涉及大量的调节过程，每一个过程都可能受到环境应激因素的独特影响。我的研究计划的长期目标是了解这些过程是如何控制的，以及它们如何让动物在压力环境中茁壮成长。在短期内，我将专注于了解控制心脏和代谢抑制的信号机制，在3个研究主题：主题1）牛磺酸对心脏功能和代谢的调节。牛磺酸大量存在于大多数动物的心肌中。已知它保护哺乳动物心脏免受应激相关损伤，影响收缩功能，并调节能量代谢，但这些功能在应激耐受性水生动物中很少受到关注。这个主题的实验将针对牛磺酸在鱼类和头足类动物中的调节功能，以确定它如何影响心脏功能和新陈代谢，以促进应激耐受性。主题2）循环性环境压力下的硬化机制。温度和氧气供应的波动在水生环境中是常见的，但我们对水生动物如何应对这种压力的理解主要是基于对单一急性压力暴露的研究。我们的初步工作表明，鱼类对周期性压力的反应不同，可能会激活新的能量保存机制，以促进生存。本主题将研究潜在的细胞和代谢过程，这些反应及其对心肺功能的影响，以确定鱼类如何在这种条件下茁壮成长。 主题3）统一工程纳米材料（ENM）毒性的机制。ENM的扩散增加了对其毒性的关注。在鱼类中，各种ENM触发代谢抑制和心肺功能障碍，使人想起对缺氧的反应，但其潜在机制尚未研究。ENM还引起炎症，其可以激活参与对缺氧的代谢和心肺反应的细胞途径。本主题将研究暴露于各种ENM的鱼类中的调节信号通路激活，以确定它们是否通过共同的受体或一组受体起作用。然后将应用药理学技术来证实阻断受体激活可以防止ENM暴露对心肺和代谢的影响。重要性：我的研究项目旨在提高我们对动物在压力环境中反应和茁壮成长的机制的理解。了解这些机制及其生理后果将使我们能够更好地预测环境变化和人类活动对水生动物的影响。

A plethora of regulatory processes are involved in the maintenance of energy balance and cardiorespiratory function in aquatic animals and each can be uniquely affected by environmental stressors. The long-term goal of my research program is to understand how these processes are controlled and how they allow animals to thrive in stressful environments. In the short term, I will focus on understanding the signalling mechanisms controlling cardiac and metabolic depression in 3 research themes: Theme 1) The regulation of cardiac function and metabolism by taurine. Taurine is present in significant quantities in the cardiac muscle of most animals. It is known to protect mammalian hearts from stress-associated damage, influence contractile function, and regulate energy metabolism but these functions have received little attention in stress-tolerant aquatic animals. Experiments in this theme will address taurine's regulatory functions in fish and cephalopods to determine how it influences heart function and metabolism to promote stress tolerance. Theme 2) Mechanisms underlying hardening in response to cyclic environmental stressors. Fluctuations in temperature and oxygen availability are common in aquatic environments but our understanding of how aquatic animals deal with such stresses are based largely on studies examining single acute stress exposures. Our initial work showed that fish respond differently to cyclic stressors and may activate novel energy conserving mechanisms to promote survival. This theme will examine potential cellular and metabolic processes underlying these responses and their impacts on cardiorespiratory function to determine how fish thrive under such conditions. Theme 3) Unifying mechanisms of engineered nanomaterial (ENM) toxicity. The proliferation of ENMs has increased concerns over their toxicity. In fish, a variety of ENMs trigger metabolic depression and cardiorespiratory dysfunction reminiscent of a response to oxygen deprivation but the underlying mechanisms have not been investigated. ENMs also cause inflammation, which can activate cellular pathways involved in the metabolic and cardiorespiratory responses to hypoxia. This theme will examine regulatory signaling pathway activation in fish exposed to a variety of ENMs to determine if they act through a common receptor or set of receptors. Pharmacological techniques will then be applied to confirm that blocking receptor activation prevents the cardiorespiratory and metabolic impacts of ENM exposure. Significance: My research program aims to improve our understanding of the mechanisms used by animals to respond to and thrive in stressful environments. Understanding these mechanisms and their physiological consequences will allow us to better predict the impacts of environmental change and anthropogenic activity on aquatic animals.