Research Project 2

研究项目2

• 批准号: 10207633
• 负责人: Michael Parsons
• 金额: $ 18.45万
• 依托单位: FLORIDA GULF COAST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10207633
• 关键词: Acute; Affect; Antioxidants; Biological Markers; Biological Models; Biosensor; Cardiovascular system; Caribbean region; Cell Line; Ciguatera Poisoning; Ciguatoxins; Communities; Consumption; Coupled; DNA Damage; Detection; Development; Diagnostic; Dinophyceae; Drug Metabolic Detoxication; Ecology; Ecosystem; Evaluation; Exposure to; Fisheries; Fishes; Food Webs; Gambierdiscus; Habitats; Harvest; Health; Health protection; Human; In Situ; In Vitro; Investigation; Island; Knowledge; Link; Metabolic Biotransformation; Metabolism; Methodology; Modeling; Monitor; Neurologic; Oxidative Stress; Pathway interactions; Planet Earth; Poisoning; Population; Prevalence; Process; Production; Proteins; Proxy; Public Health; Research; Research Project Grants; Resources; Risk; Seafood; Services; Severities; Source; Sulfur; Symptoms; Syndrome; Toxic effect; Toxicology; Toxin; Ursidae Family; Work; Zebrafish; advanced analytics; bioaccumulation; climate change; coral; detection method; exposed human population; gastrointestinal; innovation; insight; method development; novel; prognostic; protective effect; remote communities; response; socioeconomics; tool

Research Project 2 will bridge the gap between knowledge of the ecology of toxigenic Gambierdiscus on the reef (established in research project 1) and human exposure and toxicity (evaluated in research project 3). Specifically, Project 2 will evaluate the metabolites produced by the toxigenic Gambierdiscus and their flux and mechanisms of transfer into the marine food web to assess the rates of bioaccumulation, mechanisms of transport and biotransformation, and depuration. We will include ecophysiology studies of both toxin and the sulfur osmolyte, dimethylsulfoniopropionate (DMSP) production Gambierdiscus. We hypothesize that DMSP, which is produced at >100 mM intracellular concentrations in Gambierdiscus, may have protective effects (possibly via antioxidant activity) against the effects of the toxin in the producers and consumers as both metabolites move through the food web. The results from these investigations will be critical for the development of toxin flux models and in the assessment of human health risk. Project 2 will also be focused on determining processes/mechanisms that are upregulated in model fish species following acute and sub-lethal exposure, to identify metabolites and biomarkers that may provide insight into the toxicological effects of ciguatoxin. Accordingly, the proposed research will focus on the use of multiple model systems of finfish, exposed to CTX, and use an integrated “omics” approach, to identify and subsequently validate biomarkers of CTX exposure, as a proxy of likely bioaccumulation. With these results we will move toward development of methods for in situ toxin detection and potential diagnostic or prognostic methodologies. These studies will be coupled with targeted investigations to evaluate cellular CTX transport mechanisms, detoxification mechanisms, DNA damage, and oxidative stress (linked with DMSP production and transformation). The novel integrated approach of project 2, will bring advanced analytical methodologies to bear on a long-standing problem of trying to provide biomarkers and forecasting tools that will ultimately limit exposure of humans to CTX.

研究项目2将弥补珊瑚礁上产脂甘比盘菌生态学知识与 （在研究项目1中确定）和人类接触和毒性（在研究项目3中评价）。 具体而言，项目2将评估产毒甘比盘菌产生的代谢物及其通量， 转移到海洋食物网的机制，以评估生物累积率， 运输和生物转化以及净化。我们将包括生态生理学研究毒素和 硫渗透剂，二甲基磺基丙酸盐（DMSP）生产Gambierdiscus。我们假设DMSP， 其在冈比亚盘菌中以>100 mM的细胞内浓度产生，可能具有保护作用 （可能通过抗氧化活性）对抗毒素在生产者和消费者中的影响， 代谢物在食物网中移动。这些调查的结果将对发展至关重要 毒素通量模型和人类健康风险评估。项目2还将侧重于确定 在急性和亚致死暴露后， 确定代谢物和生物标志物，以深入了解雪卡毒素的毒理学效应。 因此，拟议的研究将集中在使用多个模型系统的鳍鱼，暴露于CTX， 并使用综合的“组学”方法，以确定并随后验证CTX暴露的生物标志物， 可能的生物累积性的代表。有了这些结果，我们将朝着原位毒素检测方法的发展迈进。 检测和潜在的诊断或预后方法。这些研究将与有针对性的 评估细胞CTX运输机制、解毒机制、DNA损伤和 氧化应激（与DMSP的产生和转化有关）。项目2的新综合办法， 将带来先进的分析方法来解决一个长期存在的问题，即试图提供生物标志物， 以及最终限制人类接触CTX的预测工具。