Receptor-based developmental and reproductive toxicity of Superfund chemicals

Superfund 化学品基于受体的发育和生殖毒性

• 批准号: 8723393
• 负责人: David M Ozonoff
• 金额: $ 7.82万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-22 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8723393
• 关键词: Address; Affect; Aging; Attention; Awareness; Bioinformatics; Biology; Boston; Cells; Chemicals; Communities; Computational Biology; Computer Simulation; Core Facility; Cyprinodontidae; Data Analyses; Data Set; Development; Developmental Process; Discipline; Ecology; Endocrine Disruptors; Environment; Environmental Health; Epidemiologic Studies; Epidemiology; Event; Exposure to; Faculty; Fishes; Funding; Fundulus heteroclitus; Future; Goals; Hazardous Substances; Hazardous Waste; Health; High Prevalence; Human; Interdisciplinary Study; Investigation; Knowledge; Laboratories; Leadership; Learning; Local Government; Mentors; Metals; Methods; Methoxychlor; Modeling; Molecular; Molecular Biology; Molecular Epidemiology; Molecular Structure; Motion; Outcome; Pesticides; Poison; Polychlorinated Biphenyls; Population; Positioning Attribute; Private Sector; Production; Productivity; Proteins; Public Sector; Reproduction; Reproductive Process; Research; Research Personnel; Research Project Grants; Research Support; Risk Assessment; Scientific Advances and Accomplishments; Scientist; Secure; Sentinel; Shapes; Signal Recognition Particle; Solutions; Spatial Distribution; Superfund; System; Techniques; Tetrachloroethylene; Thinking; Toxic Actions; Toxic effect; Toxicology; Toxin; Training; Translating; Universities; Work; Xenobiotics; Zebrafish; authority; base; cost effectiveness; design; disease registry; drinking water; interdisciplinary approach; interest; meetings; member; next generation sequencing; novel; phthalates; programs; receptor; reproductive; sound; superfund chemical; superfund site

The scientific theme for the Superfund Research Center at Boston University is receptor-based toxic effects of Superfund chemicals on development and reproduction in humans and wildlife. The chemicals under study are organic compounds of special interest to the SRP Center mandate that initiate their toxic actions by interacting with specific molecules inside cells called receptors. This interaction sets in motion chain of events that often leads to production of new proteins that alter the development of the cells. The research ranges from basic laboratory investigations to large scale epidemiologic studies of populations exposed through drinking water or around a Superfund site or molecular studies of fish ecology in a contaminated harbor. The object is to gain a better understanding of the implications of disturbances of reproductive and developmental processes, including aging, from exposures to hazardous substances in the environment. A special feature is a coordinated set of parallel projects examining molecular and population effects of developmental toxins in the standard laboratory zebra fish model and a widespread environmental sentinel, the killifish. Epidemiological studies of developmental outcomes from exposure to the high-prevalence Superfund chemicals perchloroethylene (PCE, tetrachloroethene), PCBs, the pesticide methoxychlor, phthalate, organotins and metals target knowledge gaps identified as special research needs by EPA/Agency for Toxic Substances and Disease Registry (ATSDR). A major feature is development of novel methods to address some of the most difficult problems associated with the typical hazardous waste epidemiological and toxicological datasets, temporal spatial distribution and interaction in mixtures. A Research Support Core provides expertise for highly sophisticated data analysis of Next Generation Sequencing and computer modeling of molecular structures, techniques used by five of the seven research projects. The Center includes two Core facilities dedicated to translating research for use in risk assessment by state and federal agencies and engaging the public and local health authorities in framing and shaping the scientific research agenda.

波士顿大学超级基金研究中心的科学主题是超级基金化学品对人类和野生动物发育和繁殖的基于受体的毒性效应。正在研究的化学物质是SRP中心特别感兴趣的有机化合物，它们通过与细胞内称为受体的特定分子相互作用来启动它们的毒性作用。这种相互作用启动了一系列事件，这些事件往往会导致新蛋白质的产生，从而改变细胞的发育。研究的范围从基础实验室调查到通过饮用水或超级基金地点周围暴露的人群的大规模流行病学研究，或对受污染港口的鱼类生态的分子研究。其目的是更好地了解环境中有害物质对生殖和发育过程的干扰，包括衰老的影响。 一个特点是一套相互协调的平行项目，在标准的实验室斑马鱼模型和广泛存在的环境哨兵--吉利鱼中检查发育毒素的分子和种群影响。对接触高流行的超级基金化学品全氯乙烯(PCE、四氯乙烯)、多氯联苯、杀虫剂甲氧氯胺、邻苯二甲酸酯、有机锡和金属所造成的发展后果的流行病学研究针对的是环境保护局/有毒物质和疾病登记机构(ATSDR)确定的特殊研究需要的知识空白。一个主要特点是开发新的方法，以解决与典型危险废物流行病学和毒理学数据集、混合物中的时间空间分布和相互作用有关的一些最困难的问题。研究支持核心为下一代测序的高度复杂的数据分析和分子结构的计算机建模提供专业知识，这是七个研究项目中的五个使用的技术。该中心包括两个核心设施，致力于将研究转化为州和联邦机构在风险评估中使用的研究，并让公众和地方卫生当局参与制定和制定科学研究议程。