Research Project 2

研究项目2

• 批准号: 10443690
• 负责人: Michael Parsons
• 金额: $ 15.26万
• 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/10443690
• 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; Work; Zebrafish; advanced analytics; bioaccumulation; biomarker identification; biomarker validation; climate change; coral; detection method; exposed human population; gastrointestinal; innovation; insight; marine; 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 将弥合珊瑚礁上有毒 Gambierdiscus 生态学知识之间的差距 （在研究项目 1 中建立）和人体接触和毒性（在研究项目 3 中评估）。 具体来说，项目 2 将评估有毒 Gambierdiscus 产生的代谢物及其通量和 转移到海洋食物网以评估生物累积率的机制、 我们将包括毒素和毒素的生态生理学研究。 硫渗透剂，二甲基磺基丙酸（DMSP）生产Gambierdiscus，我们欺负DMSP， Gambierdiscus 中产生的细胞内浓度 >100 mM，可能具有保护作用 （可能通过抗氧化活性）对抗毒素对生产者和消费者的影响 代谢物通过食物网移动，这些研究的结果对于发展至关重要。 毒素通量模型和人类健康风险评估项目 2 也将重点确定。 模型鱼类在急性和亚致死暴露后上调的过程/机制， 识别代谢物和生物标志物，可以深入了解雪卡毒素的毒理学作用。 因此，拟议的研究将集中于使用暴露于 CTX 的有鳍鱼类的多个模型系统， 并使用综合“组学”方法来识别并随后验证 CTX 暴露的生物标志物，作为 有了这些结果，我们将致力于开发原位毒素的方法。 这些研究将与有针对性的方法相结合。 研究评估细胞 CTX 转运机制、解毒机制、DNA 损伤和 氧化应激（与 DMSP 生产和转化相关）。项目 2 的新颖综合方法， 将采用先进的分析方法来解决试图提供生物标志物这一长期存在的问题 最终将限制人类接触 CTX 的预测工具。