Research Project 3

项目摘要 P01赠款标题：大加勒比雪卡特拉研究中心 项目3标题：翻译：人类遗传毒性和细胞代谢的机制 项目3与项目1和项目2相互联系，提供了人体细胞在暴露于 分离出的雪卡毒素。此处的发现将与项目负责人和管理核心共享，以 向社区参与核心提供全面的信息流，以便定期分发内容 以及对受影响的利益攸关方的认识。以项目1的建模为指导来理解 在该地区的冈比亚种群动态，项目2将产生分离的冈比亚衍生毒素， 包括整个食物网的生物积累的细节。项目3团队将与项目密切合作 2铅(艾莉森·罗伯逊)阐明并发现CTX暴露的遗传毒性机制，暴露如何变化 (急性与慢性)以及暴露是否会影响对其他环境因素的二次暴露。最后，项目3 将评估亚细胞串扰的详细机制，可能揭示与以下相关的新生物标记物 曝光。如将在整个研究计划中详细描述的那样，这将使用新颖的、 由Sobol实验室开发和优化的最先进技术，包括一种新的基因毒素筛选 平台(CometChip)提供的容量和灵敏度是以前的10,000倍以上 遗传毒性分析方法，钙信号和代谢物的新型高分辨率细胞成像工具 (ATP，NAD+)量化，细胞死亡机制，线粒体功能和基因组信号反应。

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.