Microarrays in Fathead Minnows and Bass

DESCRIPTION (provided by applicant): Microarrays are a powerful way to measure the biological impact of contaminants in the environment. Because they are used to test changes in expression of many genes in parallel, they provide data on the mechanisms by which compounds affect health more quickly than methods now in use, which makes them much less expensive than current tests. Today, gene chips (microarrays) are an established technology in human disease research. The purpose of the Phase I grant we just completed and this proposed continuation is to bring their power and precision to environmental toxicology. By understanding how contaminants affect gene expression in fish and other wildlife, we can begin to link environmental exposures to adverse health effects in these animals and by extrapolation, to humans. In this Phase II proposal, EcoArray intends to develop, validate and begin to market large oligonucleotide-based glass microarrays for fathead minnows and largemouth bass and develop the backbone of a powerful database. In Phase III, we will use knowledge obtained in this grant to finalize our product offering of a suite of general- and special-purpose microarrays for research and environmental monitoring by Academia, Government and Industry. Our successful Phase I grant validated the use of arrays for a small set of environmental contaminants and resulted in prototype arrays for the two species, as described in our publications, presentations and posters. Our goal for this Phase II work is to expand the current arrays to a larger, more robust format, resulting in a 10,000+-gene fathead minnow microarray and 2,000+ gene largemouth bass microarray. We have engaged five collaborators, all of whom are experts in fish biology, to carry out exposures and field analysis in fathead minnows or largemouth bass. For the fathead minnow studies, we will use the microarrays that we will develop to identify and characterize the genetic signatures for 14 different compounds commonly found at superfund sites, and that are known to have distinct modes of action. Many of these compounds are on the 2003 Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) Priority list. We are currently involved in a collaboration (CRADA) with the EPA to pick the best microarray platform and validate its use, and this commercial platform will be the basis for our enhanced microarrays. We will incorporate the gene expression data into a relational database that will also include other parameters such as water chemistry data and biological and physiological endpoints in the treatment species. We will conduct similar laboratory and field studies, but on a smaller scale, in largemouth bass and identify and characterize the genetic signatures for 5 different compounds. We have begun our marketing plan, and have had early success in selling laboratory services associated with gene discovery. We expect to offer an oligonucleotide-based chip developed with the EPA in late 2005 and then begin our marketing launch of the chips developed in this grant, as well as several other complementary products, in late 2006.