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，多溴的海洋天然产物（例如内分泌中的多溴二苯基醚，二恶英和吡咯菌）在海洋食品网中的生物磁化，可通过海鲜通过海鲜传播到人类中。另外，天然产生的挥发性多溴甲烷是极有效的臭氧破坏性剂。尽管它们公认的有毒潜力和有害的环境影响，但尚未阐明在海洋代谢组中产生这些多溴分子的途径。反过来，这阻碍了发现和查询其他天然来源的生物合成潜力的工具，这些天然来源将这些多溴污染物引入环境中。 从生物化学家的角度来看，本应用中概述的研究策略对这些分子进行了重新研究，并使用跨学科的元基因组采矿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影响是由研究海洋无脊椎动物和藻类的重点证实的，这些海洋无脊椎动物和藻类是这些分子的自然自然产生者。提供了引人注目的初步数据，以支持该提案中先进的生物合成假设，并提出了遗传和生化实验的组合来严格检验这些假设。在基于质谱的分析投资中，本研究过程中产生的数据将用于推动发现潜在的额外天然来源，这些天然来源有助于人类和环境暴露于这些天然产生的多溴污染物。此外，研究设计认可并试图探索众多的机会，这些机会将为卤化酶学和新型海洋生物化学的发展而展示。总体而言，研究设计促进了一项创造性，独立的研究计划的制定，该计划将对后来的独立资金竞争，这将有助于推进NIH的任务。 该应用程序旨在补充Agarwal博士先前的研究经验，并在修订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制职位。 Agarwal博士的主要门数摩尔博士和同事艾伦博士被仔细选择其潜水员和互补的科学专业知识，以涵盖拟议研究的所有要素。此外，Agarwal博士已经组成了一个由三个合作者组成的团队，以提供特定的科学贡献，并为海外和顾问的三个会员科学咨询委员会委员会就其科学进步和职业发展提供。所有导师，合作者和顾问都是高级科学家，在过渡到独立学术职业的咨询博士后科学家方面都有丰富的经验。