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，多溴海洋天然产品，如干扰内分泌的多溴二苯醚、二恶英和吡咯，在海洋食物网中产生生物放大作用，并可通过海产食品传给人类。此外，天然产生的挥发性多溴甲烷是极其有效的臭氧破坏剂。尽管其公认的潜在毒性和有害的环境影响，但这些多溴分子在海洋代谢组中的产生途径尚未得到阐明。这反过来又阻碍了开发工具来发现和查询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战略从生物化学家的角度重新审视这些分子，并使用跨学科宏基因组挖掘方法来表征多溴污染物和毒素的生物合成途径。研究设计的生态和人类健康的影响得到证实的重点是调查海洋无脊椎动物和藻类，这些分子是非常多产的自然生产者。提供了令人信服的初步数据来支持本提案中提出的生物合成假设，并提出了遗传和生物化学实验的组合来严格测试这些假设。在这项研究过程中产生的数据将被用于推动发现未得到充分重视的其他自然来源，这些来源导致人类和环境接触这些自然产生的多溴污染物。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发展提供的众多机会。总体而言，研究设计促进了一个创造性的，独立的研究计划，将有竞争力的后续独立的资金，这将有助于推进国家卫生研究院的使命的发展。 该应用程序旨在补充Agarwal博士先前的研究经验，并在指导阶段为他提供实质性的技术和智力培训，以过渡到独立的终身职位。Agarwal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，因为他们具有多样和互补的科学专业知识，涵盖了拟议研究的所有要素。此外，Agarwal博士还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，以及一个由三名成员组成的科学咨询委员会，以监督他的科学进展和职业发展并提供建议。所有导师，合作者和顾问都是资深科学家，在为博士后科学家过渡到独立的学术生涯提供咨询方面拥有丰富的经验。