SBIR-STTR Award

Genomics, the global genetic analysis of organisms, simultaneously reports both specific and holistic assessments of biological systems. Genomic approaches are therefore ideally suited for the assessment of potential impacts of chemicals on ecosystems and the environment. To date, however, genomics infrastructures have not been developed for any of the commonly used and accepted ecotox/environmental monitoring organisms. Yet environmental and ecosystem toxicity has both direct and indirect impact on human health. In this proposal we will test the feasibility of developing and using microarrays for the common environmental sentinel organisms. Specifically, in this Phase I work we will construct a pilot array for Daphnia pulex. Developing this Daphnia pilot array will test feasibility of 1) developing reasonably comprehensive arrays in Phase II, 2) identifying toxic chemicals based on their expression signature, and 3) gauging chemical concentration and dose response based on expression changes. We will test the response of the arrays to the EPA?s 12 persistent bio-accumulative toxins (PBT?s). If this work proves feasibility, Phase II will involve development of a reasonably comprehensive Daphnia array and beginning arrays for fathead minnow, duckweed, and green algae. PROPOSED COMMERCIAL APPLICATION: Eon will develop and market DNA microarray-based tests for rapid and economical assessment of a chemical or effluent sample's potential toxicity to ecosystems. These tests will be sold to chemical industry and regulatory agency customers. Chemical companies using our technology will reduce time to market and cradle to grave costs. To regulatory concerns, Eon will provide a far more detailed and useful picture of chemical impacts.

Thesaurus Terms:
environmental toxicology, gene expression, genome, microarray technology, technology /technique development Osteichthyes, algae, genetic library, nucleic acid quantitation /detection, nucleic acid sequence

Genomic methods simultaneously report both specific and holistic assessments of biological systems an ideal property when assessing the potential impact of chemicals on ecosystems and the environment. To date, however, genomics infrastructures have not been developed for one of the most commonly used and accepted environmental toxicity monitoring organisms Ceriodaphnia dubia. In this Phase II proposal, we expand on our Phase I work by sequencing a large number of C. dubia cDNAs using high-throughput sequencing. After sequence assembly and annotation, we will print a 4x70,000-element oligonucleotide microarray representing at least 10,000 distinct genes. This array will be used to perform toxicity tests on four reference toxins with different chemical properties. Each of the chemicals tested will be assayed at three different concentrations. We will define expression signatures for each of the toxins and attempt to correlate expression results with known toxicity mechanisms. In addition, we will perform one 7-day exposure at a low concentration of a toxin known to have chronic effects and note how the expression profile changes over time. Finally, we will assemble a highly annotated Ceriodaphnia database that has been integrated into a bioinformatics infrastructure that will allow easy interpretation and sharing of hybridization data.This project aims to develop DNA microarrays for the identification and understanding of environmental toxicity in the one of the key organisms used for testing environmental toxicity the water flea Ceriodaphnia dubia. DNA microarrays are a uniquely powerful method of identifying and characterizing environmental toxicity due to their ability to combine many specific tests to achieve a global understanding of toxic effects. High throughput DNA sequencing and NimbleGen based array synthesis will be used to produce fully annotated and commercial ready microarrays for use both in academic and commercial settings. In addition to commercially available Ceriodaphnia microarrays, Eon Corporation will facilitate use of these arrays through contracted performance of microarray based tests, and distribution of an expression analysis database that incorporates identification, function, and expression information for each element/gene. Technologies for environmental toxicity testing have fallen 15 years behind those now commonly used in pharmaceutical toxicity testing. Without new technologies for identifying and characterizing environmental toxins, the increasing variety and quantity of chemicals released into the environment will mount untold environmental and human health tolls.

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Thesaurus Terms:
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