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将弥合礁石上毒素gambierdiscus生态学知识之间的差距 （在研究项目1中建立）以及人类暴露和毒性（研究项目3中评估）。 具体而言，项目2将评估Toxigenic Gambierdiscus及其通量和其助剂和其助剂的代谢产物 转移到海洋食品网的机制，以评估生物积累率 运输和生物转化和部署。我们将包括毒素和毒素的生态生理研究 硫渗透液，二甲基磺胺二丙酸酯（DMSP）生产GambierDiscus。我们假设DMSP， 在gambierdiscus中以> 100 mm的细胞内浓度产生的作用可能具有保护作用 （可能是通过抗氧化活性）反对毒素在生产者和消费者中的影响 代谢物通过食物网。这些调查的结果对发展至关重要 毒素通量模型和人类健康风险的评估。项目2还将重点放在确定 急性和亚致死暴露后，在模型鱼类中上调的过程/机制， 鉴定可能提供有关雪茄毒素毒理学作用的代谢物和生物标志物。 彼此之间，拟议的研究将集中于使用多种模型系统，这些模型系统暴露于CTX， 并使用综合的“ OMICS”方法来识别并随后验证CTX暴露的生物标志物作为一个 通过这些结果，我们将朝着开发原位毒素的方法 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传输机制，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的新颖综合方法， 将带来先进的分析方法，以解决试图提供生物标志物的长期存在的问题 并预测最终将限制人类接触CTX的工具。