Use of multi-omic approaches to enable non-lethal biological effects monitoring of wild fish

我研究计划的长期愿景是促进对淡水鱼和其他脊椎动物血浆功能的了解，并建立血浆在环境影响监测计划中用作非致命性诊断工具的潜力。这项研究计划将开发和演示如何将高通量分子方法和生物信息学软件工具的使用纳入环境监测和评估计划的政策和程序。这些方法将能够确定暴露在改变脂肪代谢的水生污染物中，并将能够预测淡水鱼的长期健康结果。我的研究计划将解决三个相互关联的目标：1.开发新的蛋白质基因组生物信息学工具，利用蛋白质组学方法对目前未测序的野生鱼类进行有效的非致命性监测；2.了解应激条件下鱼类血浆中分子表达的生理原因，以及与代谢和生物能量功能相关的分子反应如何受到自然环境中的挑战的影响-目的是在现实的压力情景下建立分子的“正常”范围。3.从机械上表征污染物如何影响新陈代谢和生物能量学：通过检查化学物质，如调脂药物和全氟化化学品的分子效应，然后确定与污染物暴露有关的独特蛋白质和代谢物生物标志物。这项研究计划将增加我们对血浆在脊椎动物生理和功能中的作用的理解。这项研究还将有助于了解存在于体内的全氟污染物的影响北美的饮用水，已知在人类和野生动物体内积累。此外，这些信息将有助于减少在研究中使用动物，并将在保护加拿大濒危和受威胁物种方面特别有用。这项研究还将有助于培养11名环境科学、分子生物学和仪器分析方面的高素质人才。这项工作将提高社会与自然和野生动物互动的能力，同时享受诸如钓鱼、露营和在湖泊和河流中游泳等运动，从而使加拿大经济受益。

The long-term vision for my research program is to advance understanding of blood plasma function in freshwater fish and other vertebrate animals and to establish the potential for plasma to be used as a non-lethal diagnostic tool in environmental effects monitoring programs. This research program will develop and demonstrate how to incorporate the use of high throughput molecular methods and bioinformatic software tools into environmental monitoring and assessment program policies and procedures. These methods will be able to identify exposure to aquatic contaminants that alter lipid metabolism and will be capable of predicting long-term health outcomes in freshwater fish. My research program will address three inter-related objectives:  1. To develop novel proteogenomic bioinformatics tools that enable the efficient non-lethal monitoring of currently un-sequenced wild fish species using proteomic approaches 2.Understand the physiological causes of molecular expression in fish blood plasma under stress, and how molecular responses that are specifically related to metabolic and bioenergetic functions are affected by challenges in their natural environment - the purpose of this is to establish "normal" ranges of molecules under realistic stressful scenarios 3.Mechanistically characterize how contaminants affect metabolism and bioenergetics by examining the molecular effects of chemicals such as lipid regulating drugs and perfluorinated chemicals and then identifying unique sets of protein and metabolite biomarkers that are specific to contaminant exposure This research program will increase our understanding of the role of blood plasma in vertebrate physiology and function. This research will also contribute to the body of knowledge about the effects of perfluorinated contaminants that are present in North American drinking water and known to accumulate in humans and wildlife. Additionally, the information will help to reduce the use of animals in research and will be especially useful in protecting endangered and threatened species in Canada. This research will also help to train 11 highly qualified personnel in environmental science, molecular biology, and instrumental analysis. This body of work will benefit Canadian economically by increasing society's ability to interact with nature and wildlife while they enjoy activities such as sport-fishing, camping, and swimming in lakes and rivers.