IIT Seminar Series: Joshua Harrill

Tue, January 30, 2024 11:00 AM - Tue, January 30, 2024 1:00 PM at 162 Food Safety & Toxicology Building

Natalie Johnson*The Institute for Integrative Toxicology presents Dr. Joshua Harrill, Center for Computational Toxicology and Exposure, U.S. EPA, to speak on, “High-Throughput Phenotypic Profiling with the Cell Painting Assay and Applications for Next Generation Risk Assessment,” on Tuesday, January 30, 2024, at 11:00 a.m. in 162 Food Safety and Toxicology Building

Researchers at the U.S. EPA have proposed a tiered in vitro and in silico chemical hazard evaluation strategy where high-throughput profiling (HTP) assays are used in the first tier to rapidly generate bioactivity data for hundreds of chemicals in a variety of human-derived cell models. High-throughput phenotypic profiling (HTPP) with the Cell Painting assay is a component of Tier 1 screening that is used to: 1) determine molecular points-of-departure (mPODs) that correspond to threshold concentrations where cellular biology is perturbed and 2) generate phenotypic profiles that characterize the biological activity(s) of the test chemicals. In Cell Painting, cells are labeled with fluoroprobes that target a variety of organelles (e.g., nucleus, endoplasmic reticulum, cytoskeleton, mitochondria, etc). Automated microscopy is then used to collect thousands of cellular images. Image analysis software is used to generate numerical information (i.e. features) describing cellular states. Concentration-response modeling is then applied to the feature data to quantify changes in cell morphology in response to chemicals.  This presentation will describe the implementation of the Cell Painting assay at US EPA and potential applications for Cell Painting data in chemical risk assessment, including bioactivity exposure ratio (BER) analysis, chemical grouping and mechanistic inference.

*Fulfills seminar requirements for the Environmental and Integrative Toxicological Sciences Graduate Programs. Seminars that fulfill this requirement are archived at: https://iit.msu.edu/training/eits/recent-seminar-list.html.