Superfund Research Program

Research Support A: Computational Modeling of Mammalian Biomolecular Responses

Project Leader: Rory B. Conolly (U.S. Environmental Protection Agency (EPA))
Co-Investigator: Qiang Zhang (The Hamner Institutes for Health Sciences)
Grant Number: P42ES004911
Funding Period: 2006-2021

Project-Specific Links

Final Progress Reports

Year:   2020  2012 

The Computational Core has served the MSU Superfund Research Center with three overarching goals. The first is to develop mechanistically-based, computational models of dioxin-like compound toxicity in support of experimental studies. Toward this goal, the research team has constructed mechanistically based B cell models that can recapitulate many of the cellular behaviors in response to dioxins. The research team has continued to work to adapt existing toxicokinetic and toxicodynamic models for TCDD that will eventually help predict human dioxin body burden. Bioinformatic analysis have revealed the unique characteristics of transcriptional network initiated by AhR, the receptor for dioxins, which allows a better prediction of the dose-response behavior of dioxins. The second goal is to conduct relevant but more independent, theoretical research aligned with SRP mandates for developing tools for assessing the dose-response relationship for hazardous substances. The team has examined many biological pathway structures that are capable of generating threshold or other nonlinear dose responses, through which point of departure can be mechanistically defined. The research team’s third goal is to provide computational toxicology training to SRP trainees and risk assessment professionals to keep them abreast of the state-of-the-science quantitative tools and their applications. Between 2014-2018 the Computational Core offered two short courses on MSU campus: “Computational Systems Biology and Dose Response Modeling” twice to a total of 23 students, and “PBPK modeling” three times to a total of 55 students. Course attendees include SRP trainees, students, faculty from MSU, other SRP universities, and local governments.