Understanding natural production of polybrominated toxins and pollutants

了解多溴毒素和污染物的自然产生

• 批准号: 9476033
• 负责人: Vinayak Agarwal
• 金额: $ 24.9万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9476033
• 关键词: Advanced Development; Advisory Committees; Affect; Algae; Anabolism; Bacteria; Biochemical; Biochemical Reaction; Biochemistry; Biological Assay; Biota; Biotin; Bromine; Career Mobility; Chemicals; Complement; Cues; Data; Data Set; Development; Diatoms; Diet; Dioxins; Ecosystem; Elements; Endocrine disruption; Environment; Environmental Exposure; Environmental Impact; Enzymatic Biochemistry; Enzymes; Exposure to; Food Webs; Fostering; Funding; Genes; Genetic; Genetic Markers; Goals; Halogens; Health; Health Policy; Homologous Gene; Human; Human Milk; Investigation; Knowledge; Lead; Libraries; Link; Marine Invertebrates; Marine Toxins; Marines; Mass Spectrum Analysis; Mentors; Metagenomics; Mining; Mission; Modeling; Molecular; Oceans; Ozone; Pathway interactions; Phase; Phytoplankton; Policies; Positioning Attribute; Production; Public Health; Pyrroles; Research; Research Design; Research Personnel; Role; Route; Scheme; Scientist; Seafood; Senior Scientist; Source; Specificity; Structure; Testing; Time; Toxic effect; Toxin; Training; United States National Institutes of Health; Work; anthropogenesis; base; career; career development; design; dibenzo(1,4)dioxin; experience; experimental study; exposed human population; gene discovery; guided inquiry; halogenation; interest; knowledge base; marine natural product; member; metabolome; metagenome; novel; persistent organic pollutants; pollutant; polybrominated diphenyl ether; programs; public health relevance; tenure track; tool development; transcriptomics

 DESCRIPTION (provided by applicant) The marine environment provides a plenitude of naturally produced organic pollutants and toxins. Of these, polybrominated marine natural products, such as endocrine disrupting polybrominated diphenyl ethers, dioxins, and pyrroles, biomagnify in the marine food web and are available to be passed onto humans via seafood. Additionally, naturally produced volatile polybromomethanes are extremely potent ozone damaging agents. Despite their recognized toxic potential and detrimental environmental impact, routes for the production of these polybrominated molecules in the marine metabolome have not been elucidated. This in turn hinders the development of tools to discover and query the biosynthetic potential of other natural sources that introduce these polybrominated pollutants into the environment. The research strategy outlined in this application takes a fresh look at these molecules from a biochemists' perspective, and uses an interdisciplinary metagenome mining approach to characterize the biosynthetic routes of polybrominated pollutants and toxins. The ecological and human health implications of the study design are substantiated by the emphasis that is laid on investigating marine invertebrates and algae that are exceptionally prolific natural producers of these molecules. Compelling preliminary data is provided to support the biosynthetic hypotheses that are advanced in this proposal and a combination of genetic and biochemical experiments are proposed to rigorously test these hypotheses. Complemented by mass spectrometry based analytical investigations, data generated during the course of this study will be used to drive the discovery of underappreciated additional natural sources that are contributing to the human and environmental exposure to these naturally produced polybrominated pollutants. Furthermore, the research design recognizes and seeks to exploit the numerous opportunities that will present themselves for the advancement of halogenation enzymology and novel marine biochemistry. Overall, the research design fosters the development of a creative, independent research program that will be competitive for subsequent independent funding and that will help advance the mission of the NIH. The application is designed to supplement Dr. Agarwal's prior research experience and to provide him with substantive technical and intellectual training during the mentored phase to transition to an independent, tenure-track position. Dr. Agarwal's primary mentor, Dr. Moore, and co-mentor, Dr. Allen, are carefully chosen for their diverse and complementary scientific expertise to cover all elements of the proposed research. Furthermore, Dr. Agarwal has assembled a team of three collaborators to provide specific scientific contributions, and a three member Scientific Advisory Committee to oversee and advise on his scientific progression and career development. All mentors, collaborators, and advisors are senior scientists and have extensive experience in advising postdoctoral scientists as they transition to an independent academic career.

 描述(由申请人提供) 海洋环境提供了大量自然产生的有机污染物和毒素。其中，多溴海洋天然产物，如干扰内分泌的多溴联苯醚、二恶英和吡咯，在海洋食物网中具有生物放大作用，并可通过海鲜传递给人类。此外，自然产生的挥发性多溴甲烷是非常有效的臭氧破坏剂。尽管它们具有潜在的毒性和对环境的有害影响，但这些多溴分子在海洋代谢物中的生产路线尚未阐明。这反过来又阻碍了开发工具来发现和质疑将这些多溴污染物引入环境的其他自然来源的生物合成潜力。 本申请中概述的研究策略从生物化学家的角度对这些分子进行了全新的审视，并使用跨学科的元基因组挖掘方法来表征多溴污染物和毒素的生物合成路线。研究设计对生态和人类健康的影响得到证实，重点是调查海洋无脊椎动物和藻类，它们是这些分子的异常多产的天然生产者。提供了令人信服的初步数据来支持这一提议中提出的生物合成假说，并提出了遗传和生化实验的组合来严格检验这些假说。与基于质谱学的分析调查相补充，在本研究过程中产生的数据将用于推动发现未得到重视的其他自然来源，这些来源有助于人类和环境暴露于这些自然产生的多溴污染物中。此外，研究设计认识到并寻求利用将为卤化酶学和新型海洋生物化学的进步而呈现的众多机会。总体而言，研究设计促进了创造性的独立研究计划的发展，该计划将对后续的独立资金具有竞争力，并将有助于推进NIH的使命。 该申请旨在补充阿加瓦尔博士以前的研究经验，并在他过渡到独立的终身教职职位的指导阶段为他提供实质性的技术和智力培训。阿加瓦尔博士的主要导师摩尔博士和共同导师艾伦博士是经过精心挑选的，因为他们拥有多样化和互补性的科学专业知识，涵盖了拟议研究的所有要素。此外，阿加瓦尔博士组建了一个由三名合作者组成的团队，以提供具体的科学贡献，并组建了一个三人科学咨询委员会，负责监督他的科学进步和职业发展并提供建议。所有的导师、合作者和顾问都是资深科学家，在博士后科学家过渡到独立的学术生涯时都有丰富的建议经验。