Molecular Mechanisms and Models of Exposure

描述(由申请人提供)： 了解我们环境中危险化学品的细胞和分子机制是一个关键的国家目标。《全面环境响应、补偿和责任法案》(CERCLA)的设立是为了了解与暴露于超级基金场地危险废物相关的公共健康风险。因此，更好地了解暴露途径和人类暴露于来自超级基金地点的不受控制的危险废物所造成的健康后果是高度优先的。加州大学圣迭戈分校SBRP的目标是实施现代科学方法，以识别和表征超级基金地点发现的水生污染物引发的基因组压力的机制。研究人员的发现表明，化学暴露会导致基因表达模式的变化，这些模式由潜在的信号转导途径控制和调节。加州大学圣迭戈分校的SBRP将测试这一假设，即可以利用超级基金站点化学物质对细胞信号和基因表达的改变来开发检测和生物修复化学毒物的生物模型。实验策略将在很大程度上依赖于重组DNA和新技术的开发，以在监测、修复和通过基因表达改变和异常细胞信号介导的毒性机制方面产生新的视角。为了实现这些目标，加州大学可持续发展学院SBRP将开展一项多学科努力，包括6个生物医学研究项目、2个非生物医学研究项目和3个研究支持核心。这项研究将得到博士培训项目的部分支持。由于调查人员所在的沿海环境以及我们靠近人口稠密的边境而产生的环境问题，造成了与水中污染物特别相关的独特的美国/墨西哥边境环境问题。通过研究、翻译和外联核心，与当地工业和社区团体建立了伙伴关系，利用正在开发的技术作为评估接触水平和预测健康风险的应用生物工具。来自加州大学圣地亚哥分校10个部门、有组织的研究单位和中心的研究人员将免费提供专业知识参与这个项目。这些联合努力预计将为导致环境疾病的分子机制提供新的见解，并提高我们对暴露于超级基金现场污染物的后果的理解。

DESCRIPTION (provided by applicant): Understanding the cellular and molecular mechanisms of hazardous chemicals in our environment is a critical national objective. The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) was established to gain knowledge on the public health risks associated with exposure to Superfund site hazardous waste. Thus, a greater understanding of the exposure pathway and the health consequences resulting from human exposure to uncontrolled hazardous waste from Superfund sites are high priorities. The goals of the UCSD SBRP are to implement modern scientific approaches to identify and characterize mechanisms responsible for genomic stress elicited by water born pollutants found at Superfund sites. Findings from the researchers have shown that chemical exposure leads to alterations in patterns of gene expression which are controlled and regulated by underlying signal transduction pathways. The UCSD SBRP will test the hypothesis that 'Alterations in cellular signaling and gene expression by Superfund site chemicals can be exploited to develop biological models for the detection and bioremediation of chemical toxicants'. Experimental strategies will rely heavily upon recombinant DNA and the development of new technologies to yield new perspectives on monitoring, remediation and mechanisms of toxicity mediated through altered gene expression and aberrant cellular signaling. To meet these goals, the UCSD SBRP will develop a multidisciplinary effort consisting of 6 biomedical research projects, 2 non-biomedical research projects and 3 research support cores. The research will be supported in part by a Ph.D. training program. The environmental problems resulting from the investigators' location in a coastal environment and our proximity to a populated border creates unique environmental US/Mexico border issues that are of special relevance to water born pollutants. Through the Research Translation and Outreach Core, partnerships have been formed with local industry and community groups to utilize developing technologies as applied biological tools for assessment of exposure levels and to predict health risk. Investigators with complimentary expertise from 10 UCSD Departments, Organized Research Units and Centers are participating in this project. The combined efforts are anticipated to provide new insights into the molecular mechanisms that lead to environmental illness and to improve our understanding of the consequences of exposure to Superfund site contaminants.