PROJECT SUMMARY Research from many laboratories, including those of Superfund investigators, has established that chemical exposure of biological systems results in expression changes of numerous RNA and protein molecules and these changes are correlated with, and are indicative of toxicity. In addition, several molecular epidemiologic studies have identified correlations between genetic polymorphisms and incidence of environmental-related disease. Toxicological monitoring increasingly involves the assessment of genetic and other molecular measurements derived from individuals and sentinel animals, for the purpose of detecting possible markers of disease susceptibility, as well as identification of early indicators of chemical effect, such as alterations in gene expression profiles due to exposure to environmental toxicants. Various targeted molecular methods as well as OMICs based approaches have been developed in recent years and continue to develop rapidly. These methods complement each other and allow for mechanistic investigations of entire biological pathways and networks, as well as their individual components. The optimal application of these state-of-the-art methodologies requires considerable expertise in a) sample preparation and processing, b) generation and quality assessment of the data, c) rigorous statistical and bioinformatics analysis, d) as well as interpretation of the complex data sets. It would be very challenging and costly for UW SRP project investigators to acquire expertise in all of the aforementioned areas. The UW SRP FGBLC addresses this challenge. It provides leadership and expertise for genomics, transcriptomics, epigenetics and proteomics based methods, as well as a service facility for UW SRP investigators that supports the study of gene-environment interactions in the context of environmental health sciences research. The UW SRP FGBLC enables SRP investigators to utilize a wide range of molecular biology and bioinformatics related methodologies suited to perform mechanistic studies and to identify markers of exposure to toxicants, impaired physiologic and neurologic function, and susceptibility to neurotoxicity induced by environmental toxicants, particularly those that are commonly present at hazardous waste sites. The UW SRP FGBCL shared resource facility provides the aforementioned leadership and expertise, as well as a large range of genomics, transcriptomics and other molecular based assays in a cost-effective and efficient manner, thereby maximizing the availability of these resources for UW SRP investigators. Thus, the UW SRP FGBCL plays a crucial role in supporting the UW Superfund Research Program's mission to identify the interactions between genetic, epigenetic and environmental factors that contribute to neurotoxicity and other physiological impairment.

PROJECT NARRATIVE The Functional Genomics and Bioinformatics Core Laboratory (FGBCL) plays a critical role in the University of Washington SRP by providing state-of-the-art molecular technologies and statistical and bioinformatics analysis methods to each of the UW SRP Research Projects. The FGBCL enables each UW SRP Research Project to use cutting edge molecular methodologies to study the adverse effects of chemical exposures on human health, wildlife, and ecosystems, in particular metals, which are ATSDR priority pollutants common to Superfund hazardous waste sites. Thus, the FGBCL contributes to the UW SRP Program's goals a) to protect public health by improving hazard remediation and disease prevention strategies, and b) to communicate these findings to NIEHS, EPA, ATSDR, state and local health departments, and community groups.