RIG: Enzymatic Detoxifying Systems for Diet-derived Chemicals in Herbivorous Marine Fish

多种化合物在许多海洋生物的防御中起着关键作用，并能影响整个生态系统的群落结构。这种复杂性在热带珊瑚礁上达到顶峰，热带珊瑚礁是众所周知的生物医学试剂勘探目标。尽管许多海洋天然产物已被研究用于生物医学活性，获得了关于其生物化学作用和作用机制的重要信息，但对捕食者克服这些防御的能力知之甚少。重要的是要了解捕食者如何应对饮食中的毒素（来自猎物的生化防御），以及这些系统如何与人类清除日常生活中遇到的外来化学物质（药物，污染物，毒素等）的能力相提并论。本项目利用草食性珊瑚鱼来定义对富含化学物质的饮食的耐受机制，这将有助于填补重要的空白：在（并依赖于）富含化学物质的珊瑚礁环境中进化而来的鱼类应该是研究异种生物耐受机制的有价值的模型。这些知识将有助于开发海洋天然产品作为人类的生物医学资源；此外，草食性鱼类的外源耐药机制将为已经得到充分研究的陆生生物（如昆虫）的机制研究提供有趣的、潜在的深刻见解。绝大多数脊椎动物是鱼类，但目前对鱼类如何耐受猎物的生化防御知之甚少，特别是在热带海洋群落中，这些机制可以被认为是高度发达的。一种最先进的遗传方法将表征S. spinus（一种广泛代表耐化学抗性热带草食性鱼类的鱼类）肝脏中表达的所有基因。这些基因将用于构建微阵列芯片，以量化基因表达在不同环境条件下的变化。所有基因序列将提交给国家生物信息中心（可在http://www.ncbi.nlm.nih.gov/上获得）。这项工作将为首次定义热带草食性脊椎动物饮食驱动的适应机制提供机会，并增加对草食性攻击的理解。关岛的岛屿社区与海洋有着密切的联系，使海洋科学成为向公众介绍与当地有关的科学概念和方法的宝贵机会，对这些公众来说，科学往往是陌生的。公开演讲和带薪暑期高中研究实习，以及生物学专业本科生和研究生的参与，将有助于扩大这些机会。更好地了解热带鱼应对饮食中异种毒素的机制，有助于资源管理工作，以尽量减少“滋扰物种”藻类（例如蓝藻和其他“有害藻华”；雪卡毒素中毒）的影响。该项目也有可能启动额外的合作努力，以生态相关的代谢组学和蛋白质组学分析棘猴。对于那些依赖海洋获取食物的人来说，了解为什么一些天然产品会持续存在于海洋食物链中，就相当于了解他们最重要资源的大小和/或安全性。

Diverse chemical compounds play critical roles in the defenses of many marine organisms and can influence the community structure of entire ecosystems. This complexity reaches a peak on tropical coral reefs, which are well-known targets for prospecting biomedical agents. Although many marine natural products have been studied for biomedical activity, yielding important information about their biochemical effects and mechanisms of action, much less is known about predators' abilities to overcome these defenses. It is important to understand how predators cope with poisons in their diet (from prey biochemical defenses) and how these systems parallel human's ability to remove foreign chemicals that are encountered in their every day lives (drugs, pollutants, toxins, etc.) This project's use of herbivorous reef fish to define mechanisms of tolerance to chemically-rich diets will help fill important gaps: Fish that have evolved in (and depend on) chemically-rich coral-reef environments should be valuable models for studying mechanisms of xenobiotic tolerance. This knowledge will help to develop marine natural products as biomedical resources for humans; and, mechanisms of xenobiotic tolerance in herbivorous fish will provide fascinating and potentially insightful counterparts to mechanistic studies in well-studied terrestrial organisms such as insects. The vast majority of vertebrates are fishes, yet little is currently known about how fish tolerate their preys' biochemical defenses especially in tropical marine communities, where these mechanisms can be assumed to be highly developed. A state of the art genetic approach will characterize all genes expressed in the liver of S. spinus, a fish species that broadly represents chemically resistant tropical herbivorous fishes. These genes will be used to build a microarray chip to quantify changes in gene expression in response to differing environmental conditions. All gene sequences will be submitted to the National Center for Biological Information (available on http://www.ncbi.nlm.nih.gov/.) This work will provide an opportunity to define diet-driven adaptive mechanisms in tropical herbivorous vertebrates for the first time, and increase understanding of herbivore offense. Guam's island community has strong ties to the ocean, making marine science a valuable opportunity for presenting locally relevant scientific concepts and methods to a public to whom science often seems foreign. Public presentations and paid summer high-school research internships and the involvement of undergraduate and graduate biology majors will help to expand these opportunities. A better understanding of tropical fishes' mechanisms for coping with dietary xenotoxins can contribute to resource-management efforts to minimize impacts from nuisance species' of alga (e.g., cyanobacteria and other 'harmful algal blooms'; ciguatera poisoning). This project also has potential for initiating additional collaborative efforts towards ecologically relevant metabolomic and proteomic analyses of S. spinus. For people that depend on the ocean for food, understanding why some natural products persist in marine food chains can be equivalent to understanding the size and/or safety of their most important resource.