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GENOMICS AND ENVIRONMENTAL RESEARCH
Citation:
Miracle, A L. GENOMICS AND ENVIRONMENTAL RESEARCH. Presented at 2003 BioNorth Conference, Ottawa, Canada, November 17-19, 2003.
Impact/Purpose:
The indeterminate condition of exposure indicator research stands to change markedly with the ability to connect molecular biological technologies with cellular or tissue effects and outcomes. Three focal areas of ecological research aim to develop a sequence of approaches where "the earliest recognizable signatures of exposure" (i.e., unique patterns of up- and down-regulated genes and proteins) are identified for numerous stressors, demonstrable in case studies and incorporated into Agency, State and Regional studies supported by EMAP and other programs.
Area 1, Computational Toxicology Research: Exposure assessment has historically been based on use of chemical analysis data to generate exposure models. While biological activity of chemicals has been recognized to be important for exposure risk assessments, measurement of such activity has been limited to whole organism toxicity tests. Use of molecular approaches will:
improve extrapolation between components of source-to-outcome continuum (source , exposure , dose , effect , outcome)
Using a systems modeling approach, gene and protein expression data, in small fish models (fathead minnow and zebrafish), will be integrated with metabolomic and histopathological data. This will assist in prediction of environmental transformation and chemical effects based on structural characteristics, and enhance quantitative risk assessments, including areas of uncertainty such as a basis for extrapolation of effects of endocrine disrupting chemicals, interspecies extrapolation, complex chemical mixtures and dose-response assessment.
Area 2, Ecological Research-Environmental Diagnostics: Development of molecular diagnostic indicators contributes to several of the GPRA Diagnostic Research Goals. Methods will employ DNA microarray technology and expression proteomics, focusing on species of relevance to aquatic ecosystem risk assessment. Significantly, these diagnostic indicators will open the door to understanding subcellular interactions resulting from exposure to complex chemical mixtures.
define relationship between genetic disposition of populations and degree/specificity of stressor-specific gene transcriptional response in aquatic organisms (fish and invertebrates)
identify of chemical mixture induced transcriptional "patterns" using microarrays and hyperspectral scanning - via collaboration with DOE Sandia National Labs
apply molecular indicators to watershed level stressor study, including pilot studies with targeted pesticides and toxins indicators
develop molecular indicators of exposure for invertebrates (Daphnia, Lumbriculus, Chironomus)
Area 3, Exposure Research in Endocrine Disruptors:
Subobjective 1: Develop exposure methods, measurement protocols, and models for assessment of risk management practices of endocrine disrupting compounds. As risk management approaches are identified and developed, there will be a need to identify, adapt and develop bioassay screening tools and other analytical methods to assess their efficacy. Measurements research will be performed to define management needs. This effort will entail cross-lab participation from NRMRL, NERL and NHEERL.
Subobjective 2: Determine extent of environmental and human exposures to EDCs, characterize sources and factors influencing these exposures, develop and evaluate risk management strategies to reduce exposures. In order to develop effective risk management strategies, it is important to understand the extent of exposures to endocrine disrupting compounds and factors influencing source-to-exposure-to-dose relationships.
apply molecular indicators of exposure to estrogenic compounds in selected wastewater treatment plants located in ten USEPA Regions
identify differential gene expression following exposure of fathead minnows to environmental androgens and androgen-like compounds
apply molecular indicators of exposu
Description:
The impact of recently developed and emerging genomics technologies on environmental sciences has significant implications for human and ecological risk assessment issues. The linkage of data generated from genomics, transcriptomics, proteomics, metabalomics, and ecology can be linked together through bioinformatics to generate a clear picture of events occurring within a given organism, or collection of organisms from source of stressor(s) through outcome of exposure. Recognition of the roles government, academic, and private industry research all provide to increase knowledge and build exposure-to-outcome databases will become important in collecting the diverse ecotoxicogenomic data sets required to effectively reduce uncertainties in comprehensive risk assessment for the environment and human health.
The power of genomics technologies offers a genome wide, dynamic picture of biological systems. The development of microarray technologies permits thousands of genes to be screened in a single experiment to establish differential gene expression in stressor-treated versus control cell and tissue populations. Microarrays have been used to study issues in pathology, pharmacology, oncology, cell biology, and recently, toxicology. With the advent of whole genome information readily available for select organisms, with the promise of additional, ecologically-relevant organism genomic information, microarrays can be generated to sample a significant portion of the globally expressed genome. Genomic information combined with microarray technology has revolutionized the ability to discern mechanistic pathways involved in disease processes, development, and toxicant action.
Several laboratories within the EPA's Office of Research and Development have come together to provide a framework for integration of genomics technologies within the risk assessment paradigm and produce a computational toxicology program for assessing risk to human health and ecosystems. The amount of data generated from such a multi-disciplinary approach will necessitate rigorous standardization of experimental design and data interpretation for using ecotoxicogenomic data in a regulatory context.