Using Gene Expression to Predict Toxicity Caused by Environmental Chemical

Safer Chemicals

National Health and Environmental Effects Research Laboratory (NHEERL)

Research Triangle Park, NC

3-12 months

This internship will use cutting-edge laboratory and computational techniques to link chemical-induced gene expression changes generated in different cell models to predictions of adverse effects in animals and humans.

Toxicogenomics can provide a mechanistic understanding of the underlying molecular events of chemical-induced toxicity. Transcript profiling which measures global gene expression changes in response to chemical exposure is a robust, data-rich approach to chemical toxicity screening. However, a major challenge when using transcript profiling is linking gene expression changes to molecular and cellular effects important in chemical toxicity. Our lab has recently made significant progress in developing computational approaches that allow prediction of the activation or inhibition of specific transcription factors important in endocrine disruption and cancer. The GRIP intern will join the lab during a very exciting time in applying these new tools to predict chemical-induced adverse effects in animals and people. The GRIP intern will participate in a project to generate transcript profiles using the latest in gene expression measurement technologies in human cells and apply computational tools for interpretation of the data. Progress will be facilitated by access to the world's largest private repository of gene expression information (>130,000 gene expression profiles). The project involves treating human cell lines with chemicals and measuring gene expression using microarray or targeted RNA-Seq technologies. The project will capitalize on the use of cell lines knocked out for genes using Crispr-Cas9. The intern will 1) identify genes that exhibit altered expression, 2) use those lists of altered genes to predict the activity of transcription factors important in endocrine disruption and cancer, and 3) link those predictions to adverse outcome pathways (AOPs; https://aopwiki.org/wiki/index.php/Main_Page) allowing assessment of adverse effects upon chemical exposure. The predictions will be used with other data to comprehensively predict the ability of chemicals at different dose levels to perturb pathways important for health and disease.

The intern will (1) be part of an active scientific research team, (2) conduct independent research, (3) learn how to design and carry out experiments, (4) learn a number of techniques including cell culture, RT-PCR, and computational techniques for measuring and interpreting transcriptomic data, and (5) have the opportunity to prepare research summaries in written and oral form. Depending on the progress made, it may be possible that the intern will be a co-author on a poster or manuscript. All NSF students who have rotated through the lab thus far are first authors on manuscripts.

Chris Corton (corton.chris@epa.gov)