Research from various laboratories, including those of SBRP investigators, has established that in vivo levels of particular biotransformation enzymes are relevant to numerous toxicological issues. For example, genetic correlates have been identified in several molecular epidemiologic investigations between particular polymorphisms in biotransformation genes and the incidence of environmental-related disease. In addition, biological monitoring has increasingly involved the assessment of genetic/molecular indices 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 biotransformation enzyme gene expression profiles due to exposure to environmental toxicants. Advances in technology supporting molecular research have led to the development of complex techniques involving these biotransformation enzyme systems, which are applicable to a broad range of experimental problems including novel remediation strategies. The long term objective of the UW SBRP Functional Genomics and Bioinformatics Core C Laboratory is to provide a service facility for UW SBRP investigators enabling novel genetic assay development, high throughput genetic and proteomic analysis, state-of-the-art quantitative gene expression and bioinformatic technologies, and correlates to environmental-related disease mechanisms. All six individual UW SBRP projects will utilize the UW SBRP Core C Laboratory and will benefit from the centralized services. These Core efforts will focus on a wide range of molecular biology- and proteomic-related technologies that may be predictive of: exposure to toxicants; impaired physiologic and neurologic function; unusual susceptibility to neurological damage from toxic agents that occur in the environment, particularly those that are commonly present at hazardous waste sites. Over the 5 year duration of this proposal, the UW SBRP Core C Laboratory will provide the following services: DNA/RNA extraction of 1,200 samples, the isolation of 625 mononuclear cell samples, processing and bioinformatic analyses of 255 GeneChips and 98 cDNA salmonoid arrays, the production of a custom """"""""SNP chip"""""""" representing up to 2,500 genetic variants and subsequent processing and genetic association analyses, the identification of up to approximately 5,000,000 genotypes, the development of 25 new TaqMan-based genotyping assays, the construction of 131 new gene expression assays, the execution of approximately 7,800 gene expression analyses, the provision of approximately 4,000 DNA sequencing gel lanes, the generation of 10 peptide derived antibodies, and the creation of 15 novel ELISAs. This shared resource provided by the UW SBRP Core C Laboratory supports implementation of the requisite functional genomic assays in a cost-effective and efficient manner, therefore maximizing the availability of these important tools for UW SBRP investigators.
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