Research Project 3

研究项目3

基本信息

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
项目类别：
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

项目摘要

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.

项目概要 P01 资助名称：大加勒比雪卡研究中心项目3名称：翻译：基因毒性和细胞代谢的人类机制项目 3 与项目 1 和 2 相互关联，提供了接触后人体细胞反应的详细信息分离出的雪卡毒素。本文的发现将与项目领导和管理核心分享为社区参与核心提供全面的信息流以进行定期内容分发以及受影响利益相关者的认识。以项目1的建模为指导来理解该地区的甘比尔圆盘菌种群动态，项目 2 将产生分离的甘比尔圆盘菌衍生毒素，包括整个食物网中生物累积的详细信息。项目3团队将与项目密切合作 2 负责人（Alison Robertson）阐明和发现 CTX 暴露的遗传毒性机制，暴露如何变化（急性与慢性）以及暴露是否会影响其他环境因素的二次暴露。最后是项目3 将评估亚细胞串扰的详细机制，这可能揭示与接触。正如整个研究计划中详细描述的那样，这将使用新颖的、由 Sobol 实验室开发并优化的最先进技术，包括新的基因毒素筛查平台 (CometChip) 的容量和灵敏度比以前高出约 10,000 倍遗传毒性分析方法、用于 Ca2+ 信号传导、代谢物的新型高分辨率细胞成像工具（ATP、NAD+）定量、细胞死亡机制、线粒体功能和基因组信号反应。