NEUROTOXIC SUPERFUND CHEMICALS AND BIOMAKERS

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Cross-disciplinary and interdependent research will be undertaken to investigate several classes of Superfund-relevant chemicals that exert toxic or mutagenic effects on biological systems, notably the mammalian brain and other parts of the developing and adult nervous system. Research will be focused on mixtures of organochlorine and benzene- related solvents, their biodegradation products and associated metabolites. Three non-biomedical projects will investigate important aspects of the microbial degradation of these environmental toxicants. One focuses on enhancing in situ anaerobic biodegradation processes in groundwater (Project B1), a second examines methods to enhance in situ aerobic co- metabolism of these chemicals (Project B2), and the third investigates the nature and requirements of the microbial community involved in the breakdown process (Project B3). Four biomedical projects address the detection and health impact of animal and human exposure to low concentrations of these hazardous chemical species. One study will develop data-driven models to examine how Superfund-derived chemical enter the human brain (Project A1); another will develop a sensitive biomarker of neurotoxicant exposure based on structure-activity relationships (Project 2). The third will address molecular mechanisms underlying the neurotoxic and neuro-oncogenic properties of Superfund chemical metabolites (Project A3). The fourth will investigate subtle impacts of chemical exposure on the development and adaptability of the immature brain (Project A4). A community-based project (Core C1) will seek to model neurobehavioral tests to disadvantaged pediatric populations exposed to Superfund chemicals with neurotoxic potential. Two Research Support Cores provide powerful, state-of-the-art technical support (Core D1), and next-generation mass spectroscopy (D3). The Outreach Core will assess the impact of Internet-based education on communities in remote locations that are at high risk for exposure to neurotoxicants in water and other media. Graduate students entering the Training Core will select from a wide range of biomedical and non- biomedical research opportunities that will provide them with a unique cross-disciplinary training. In sum, this program of research seeks innovative methods to promote microbial degradation and thereby reduce exposure to hazardous chemicals, to develop hazardous sensitive methods to detect their presence in environmental media and mammalian species, and to define their potential adverse effects on the developing and mature nervous system.