CAREER: Mechanistic Toxicity Assessment of Emerging Pollutants via Prokaryotic Real-Time Gene Expression Profiling for Water Quality Monitoring

职业：通过用于水质监测的原核实时基因表达谱对新兴污染物进行机械毒性评估

• 批准号: 0953633
• 负责人: April Gu
• 金额: $ 42.71万
• 依托单位: Northeastern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0953633&HistoricalAwards=false
• 关键词: CAREER; Mechanistic; Toxicity; Assessment; Emerging

0953633GuThe health risk and harmful environmental impacts associated with the plethora of emerging contaminants in our water necessitate a breakthrough in toxicity-assessment technology because the available methods are neither feasible nor sufficient to provide the timely information needed for regulatory decision making to eliminate these threats. The objectives of this CAREER project are (1) to apply an innovative interdisciplinary approach of prokaryotic real-time gene-expression profiling as a means of evaluating toxic effects and identify toxicity mechanisms of emerging contaminants; (2) to develop a more sophisticated and informative, yet cost-effective and feasible genomic assessment system for monitoring and quantifying toxicity effects from contaminants in water samples; and (3) to establish a creative and integrated education program to attract and educate personnel from various disciplines and backgrounds, especially women and underrepresented groups, to become contributors in the field of environmental engineering. The long-term goal is to build a unique interdisciplinary and translational research and education program that specializes in applying genomic and molecular biotechnology for water-quality improvement and monitoring. The lack of sufficient and feasible methods of toxicity evaluation and quantification greatly hampers the development and implementation of effective regulations, strategies, and technologies for controlling and eliminating the harmful effects from the emerging contaminants of concern. This project will, for the first time, apply a prokaryotic whole-cell array consisting of a large number (~2000) of bioluminescent GFP-transformed E. coli strains to obtain real-time gene-expression profiling in response to contaminants. The high-resolution and high-throughput measurements of the global molecular status of an organism in exposure to a toxin will allow for simultaneous evaluation of toxic effects, understanding of toxicity mechanisms, and obtaining of pollutant-specific molecular fingerprints (biomarkers) for compound classification and identification. This approach will lead to more timely and more informative toxicity-evaluation results than conventional methods. It will greatly improve the feasibility and cost effectiveness of gene-expression profiling for toxicity assessment as a result of its much simpler, faster, and more reliable assay procedure, higher reusability, and desirable flexibility for customization of the cell-array library. Furthermore, the proposed method has higher sensitivity and specificity than the existing microarray-based genomic profiling approach because it adds a temporal dimension to the profiling data and therefore allows for more comprehensive and accurate toxicity evaluation of pollutants. Obtaining a wealth of new data on the toxicity effects and toxic mechanisms for various categories of emerging environmental pollutants will help to fill a great void in our understanding of the risk of emerging contaminants. Incorporation of this information into the standard tiered ecological-risk-assessment framework can greatly advance the efficiency of regulatory ecotoxicology by reducing the uncertainty in risk assessment and optimizing the resource utilization on chemicals with the greatest potential risk. This cross-disciplinary project will incorporate its research products into an education plan built upon an interdisciplinary, experiential, and multi-channel education and outreach paradigm that will target personnel from various levels and backgrounds, including students from K-12 to graduate level, water professionals and practitioners, local agencies and regulators, and high school and community college teachers. This study will demonstrate the ability and advantages of genomic toxicity-assessment methodology as an alternative to conventional tests of toxicity evaluation and identification and/or as a complementary tool to conventional tests.The results of this research will have a significant impact on ensuring water quality for public health protection and quality-of-life improvement. This project integrates the diverse disciplines of biotechnology, toxicology, and environmental engineering and opens new ground for research in genomic toxicity assessment for water-quality monitoring. The creative and integrated teaching and education paradigm will increase the diversity of participation in the environmental engineering workforce and equip students with adequate knowledge and skills to tackle today's challenging environmental issues. The BEST (Biotechnology for the Environment-Showcase and Training) program that was pioneered by the PI will continue to expand through connections with various NU education programs (STEM, FURI, RET, and YSP) and local organizations and communities to increase the diversity of participants in the field of environmental engineering, especially with regard to women, minorities, and people with disabilities. Enhanced technology transfer and information dissemination will be achieved through ITRI (Industrial Translational Research Initiative, initiated by the PI), multi-level collaborations, and the NU co-op program. The support for the PIs career development will help her mature into a successful scholar and educator who benefits society by contributing to the technological and educational advancement of water-quality improvement and public health protection.

0953633 GuThe health risk and harmful environmental impacts associated with plurality of emerging pollutants in our water necessary a breakthrough in toxicity-assessment technology，因为现有的方法既不可行也不足以提供及时的信息，需要监管决策，以消除这些威胁。 本CAREER项目的目标是：（1）应用原核实时基因表达谱的创新跨学科方法，作为评估毒性效应和识别新兴污染物毒性机制的一种手段;（2）开发一种更复杂、信息量更大、更具成本效益和可行性的基因组评估系统，用于监测和量化水样中污染物的毒性效应;以及（3）建立一个创造性和综合性的教育计划，以吸引和教育来自不同学科和背景的人员，特别是妇女和代表性不足的群体，成为环境工程领域的贡献者。长期目标是建立一个独特的跨学科和转化研究和教育计划，专门应用基因组和分子生物技术进行水质改善和监测。 缺乏足够和可行的毒性评估和量化方法，极大地阻碍了控制和消除新兴污染物有害影响的有效法规、战略和技术的制定和实施。 本项目将首次应用由大量（~2000个）生物发光GFP转化的E.大肠杆菌菌株获得实时基因表达谱响应污染物。 对接触毒素的生物体的整体分子状态进行高分辨率和高通量测量，将能够同时评价毒性效应、了解毒性机制，并获得污染物特异性分子指纹（生物标志物），用于化合物的分类和鉴定。 与传统方法相比，这种方法将产生更及时、信息量更大的毒性评价结果。 它将大大提高基因表达谱毒性评估的可行性和成本效益，因为它更简单，更快，更可靠的测定程序，更高的可重复使用性，和理想的灵活性定制的细胞阵列库。 此外，所提出的方法具有更高的灵敏度和特异性比现有的基于微阵列的基因组分析方法，因为它增加了一个时间维度的分析数据，因此允许更全面和准确的毒性评价污染物。 获得大量关于各类新出现的环境污染物的毒性效应和毒性机制的新数据，将有助于填补我们对新出现的污染物的风险的理解方面的巨大空白。 将这些信息纳入标准的分层生态风险评估框架，可以大大提高监管生态毒理学的效率，减少风险评估的不确定性和优化资源利用的化学品具有最大的潜在风险。 这个跨学科项目将把其研究成果纳入一个教育计划，建立在一个跨学科的，经验式的，多渠道的教育和推广模式，将针对来自不同层次和背景的人员，包括从K-12到研究生水平的学生，水专业人员和从业人员，地方机构和监管机构，以及高中和社区大学教师。 本研究将展示基因组毒性评估方法作为常规毒性评估和鉴定方法的替代和/或作为常规检测方法的补充工具的能力和优势，本研究的结果将对确保水质以保护公众健康和改善生活质量产生重大影响。 该项目整合了生物技术，毒理学和环境工程的不同学科，并为水质监测的基因组毒性评估研究开辟了新的领域。 创造性和综合性的教学和教育模式将增加环境工程劳动力参与的多样性，并使学生具备足够的知识和技能，以应对当今具有挑战性的环境问题。 由PI开创的BEST（环境生物技术展示和培训）计划将继续通过与各种NU教育计划（STEM，FURI，RET和YSP）以及当地组织和社区的联系进行扩展，以增加环境工程领域参与者的多样性，特别是关于妇女，少数民族和残疾人。 加强技术转让和信息传播将通过伊特里（工业转化研究计划，由PI发起），多层次合作和NU合作计划实现。对PI职业发展的支持将帮助她成长为一名成功的学者和教育家，通过促进水质改善和公共卫生保护的技术和教育进步来造福社会。