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 

As the global effort of Toxicity Testing in the 21st Century is unfolding, demand for training of prospective toxicologists on computational skills is on the rise. The research team were particularly encouraged by the positive response to the computational modeling course the researchers offered to MSU graduate students 3 years ago. As the NIH support for the Superfund project was winding down in the first quarter of this year, the Computational Core staff decided to focus its limited resource on offering another “Computational Systems Biology and Dose Response Modeling Short Course” at MSU campus on May 22 – 24, 2012. Significantly updated from the previous course, the workshop covered common themes in signal transduction and gene regulatory networks that underlie systems-level cellular behaviors, including linear and nonlinear response motifs, homeostasis, adaptation, binary cell fate decisions, and stochasticity in gene expression. A number of specific biological examples were discussed in detail, including ultrasensitivity and bistability in MAP kinase signaling cascades, checkpoint control in the eukaryotic cell cycle, and network mapping from functional genomics data. Lectures on the various topics were accompanied by computer exercises of cellular responses using the Berkeley Madonna® simulation program. Implications for toxicology and dose-response modeling were emphasized throughout the course. The modeling work by the Computational Core in collaboration with Dr. Kaminski’s project (Characterization of the Pathways Linking Ah Receptor Activation with Altered B Cell Differentiation Using an Integrated Experimental and Computational Modeling Approach) on disruption of antibody response by TCDD was illustrated as a case study. The workshop was attended by seventeen students, most of which were graduate students from various biological sciences programs at MSU. Scientists from U.S. Fish and Wildlife Service and Dow Chemical Company also attended. The workshop received high scores in evaluation from the attendees on various aspects, including material, instruction, accessibility, and course value.