Research Project 3

研究项目3

• 批准号: 10443691
• 负责人: Robert W Sobol
• 金额: $ 13.42万
• 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/10443691
• 关键词: Acute; Affect; Aging; Apoptosis; Autophagocytosis; Awareness; Biological; Caribbean region; Cell Death; Cell Survival; Cells; Chemicals; Chronic; Ciguatera Poisoning; Ciguatoxins; Collaborations; Communication; Complex; Cytotoxic agent; Cytotoxin; DNA Damage; DNA Repair Inhibition; DNA Repair Pathway; Dangerousness; Defect; Disease; Environment; Exposure to; Food Webs; Functional disorder; Gambierdiscus; Gene Mutation; Genes; Genome; Genomics; Grant; Health; Homeostasis; Human; Imaging Device; Lead; Malignant Neoplasms; Metabolic; Metabolism; Mitochondria; Modeling; Mutagens; Necrosis; Nerve Degeneration; Neurologic; Nuclear; Organism; Pathogenesis; Pathway interactions; Phenotype; Poisoning; Population; Population Dynamics; Process; Recovery; Research; Research Project Grants; Resolution; Signal Transduction; Source; Stress; Symptoms; Syndrome; System; Technology; Tissues; Toxin; Translations; Work; bioaccumulation; biomarker development; cellular imaging; community engagement; cytotoxic; environmental agent; exposed human population; foodborne; gastrointestinal; genome integrity; genotoxicity; harmful algal blooms; in vitro Model; mitochondrial dysfunction; novel; novel marker; remediation; response; screening; stem cells; tool

Project Summary P01 Grant Title: Greater Caribbean Center for Ciguatera Research Project 3 title: Translation: Human mechanisms of genotoxicity and cellular metabolism Project 3 inter-relates with Projects 1 and 2 by providing details of human cellular response following exposure to the isolated Ciguatoxins. Discoveries herein will be shared with the Project leads and Administrative core to provide a comprehensive information flow to the Community Engagement Core for regular content distribution and awareness to the effected stakeholders. Guided by the modeling of Project 1 to understand Gambierdiscus population dynamics in the region, Project 2 will yield the isolated Gambierdiscus-derived toxins, including details on bioaccumulation throughout the foodweb. The Project 3 team will work closely with the Project 2 lead (Alison Robertson) to clarify and discover genotoxicity mechanisms of CTX exposure, how exposure varies (acute vs chronic) and if exposure impacts secondary exposure to other environmental agents. Finally, Project 3 will evaluate detailed mechanisms of subcellular crosstalk that may reveal novel biomarkers associated with exposure. This will be accomplished, as will be described in detail throughout the Research Plan, using novel, state-of-the-art technologies developed by and optimized in the Sobol lab, including a new genotoxin screening platform (CometChip) that provides greater than ~10,000-fold greater capacity and sensitivity than previous genotoxicity analytical approaches, novel high-resolution cellular imaging tools for Ca2+ signaling, metabolite (ATP, NAD+) quantification, cell death mechanisms, mitochondrial function and genomic signaling response.

项目摘要 大加勒比雪卡毒研究中心（Greater Caribbean Center for Ciguatera Research） 项目3标题：翻译：人类遗传毒性和细胞代谢机制 项目3与项目1和项目2相互关联，提供了暴露于以下物质后人体细胞反应的详细情况： 分离的雪卡毒素此处的发现将与项目负责人和管理核心共享， 为社区参与核心提供全面的信息流，以定期发布内容 并向受影响的利益相关者宣传。以项目1的建模为指导， 项目2将产生分离的冈比亚盘鱼衍生毒素， 包括整个食物网中生物累积的详细情况。项目3团队将与项目 2铅（艾莉森罗伯逊），以澄清和发现CTX暴露的遗传毒性机制，暴露如何变化 （急性与慢性）以及接触是否影响到对其他环境因子的二次接触。最后，项目3 将评估亚细胞串扰的详细机制，这些机制可能揭示与 exposure.如整个研究计划中详细描述的那样，将使用新的， 由Sobol实验室开发并优化的最先进技术，包括新的遗传毒素筛选 平台（CometChip），容量和灵敏度比以前的产品高出约10，000倍 遗传毒性分析方法，用于Ca2+信号传导的新型高分辨率细胞成像工具，代谢产物 (ATP NAD+）定量、细胞死亡机制、线粒体功能和基因组信号传导应答。