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） 海洋环境会产生有机污染物和TESE的毒素。潜在的和有害的环境影响，在海洋代谢组避风港中生产这些多溴分子的途径。 。 从生物化学家的角度来看，这些分子的研究策略是ry metagen挖掘的。这些分子的初步数据被提供给该提案中先进的Suosynthetic假设，并且组合和生物化学实验是由严格测试这些假设的严格测试的。人类和环境的预言产生了多溴的污染。这将有助于推进NIH的任务。 该应用程序旨在补充指导阶段的雨水，以过渡到独立的终身制位置，艾伦博士是为了涵盖拟议研究的所有要素，以供多样化和互补的专业知识。阿加哈尔（Agarhal）组成了一个由三个合作者组成的团队，咨询委员会负责监督和建议他的科学计划发展，以建议博士后科学家向独立学术生涯过渡。