The experimental and computational analysis of EDC impact on cellular signaling and behavior is an innovative approach to address this challenging problem. The iterative experiment model experiment design will enable the discovery of mechanisms that are specifically impacted by EDC treatment. Additionally, the proposed methods to generate signaling data sets in silico will lead to the development of new modeling techniques and refinement of the original model to handle the complicated and multivariate problem of exposure to EDC combinations. The ultimate goal is to develop models that can interpret the complicated role of ER signaling in both normal and disease states, which is an essential component of addressing women's health concerns. The effects of EDCs are a global concern and the proposed systems biology methods are essential to contend with the complexity of the problem. Development of in silico models to identify cellular mechanisms that EDCs impact and predict the result of exposure to combinations is an essential step towards preventing harmful effects from EDCs. Additionally, the outlined framework of experimental data collection and model development and analysis can be applied to essentially any biological network, providing the basis for future studies of the impact of estrogenic signaling on cellular behavior. The outlined proposal to incorporate students from non-PhD granting institutions into the research laboratory and to perform outreach to K-12 students will help to develop the next generation of students trained at the math-biology interface, and will equip students and fellows trained in the laboratory to be effective interdisciplinary researchers and teachers.
