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Development of a Genomic Screening Tool for Identifying Gene Expression Patterns
Objective:
Develop a genomic screening tool (DNA microarrays) for identification of unique patterns of genes that are "turned on" or "turned off" by specific environ- mental stressors.
Approach:
The ongoing effort to build a gene sequence database for the USEPA standard aquatic toxicological model (fathead minnow) will enhance the capability to assess changes in gene expression resulting from environmental exposure in aquatic ecosystems. More importantly, changes in patterns of gene expression, resulting from exposure to complex environmental mixtures (multiple stressors), can be effectively assessed using this type of molecular platform, and subsequently compared to patterns arising from a single stressor. Signatures of gene expression for specific stressors will then be used to develop specific, diagnostic exposure indicators, which is a vital component in the development of non-invasive computational models for toxicological risk assessment.
Why This Research Is Needed:
A better understanding of the pathways from exposure to outcome can be achieved for building computational toxicology. This technology will ultimately reduce the uncertainty in assessing risk of stressors in the environment.
EERD Experience:
Custom oligo microarrays have been constructed on a CodeLink (Amersham) platform which incorporate 125 distinct probes. These arrays are currently being used to assess gene expression changes across multiple variables such as dose, duration of exposure, chemical class, and tissue as a part of a Cooperative Research and Development Agreement with MED-Duluth and EcoArray.
Expected Outputs/Outcomes:
- Identification of disrupted cellular pathways, through computational toxicology, will forecast temporal and spatial ecological exposures and gauge the success of aquatic populations.
- Indicators of exposure will be provided; this technology is readily transferable.
- Ecological risk assessor will have the tools required for informed decision making.
Partners: Joint Genome Institute, DOE, Sandia National Laboratory, EcoArray, LLC.
Other ORD Labs: MED-Duluth, MN
Contact: David Lattier (lattier.david@epa.gov) | Ann Miracle (miracle.ann@epa.gov) (Cincinnati, OH)