Computational Biophysical Chemistry of Homeostasis and Adaptation in Mammalian Cells
This project proposes to integrate the known literature into a computer model of mammalian cellular signal transduction and transcriptional regulation, then to test and refine this model based on data. One goal is to accurately predict cellular mRNA concentrations based on the thermodynamics of molecular interactions. Since the fundamental laws of thermodynamics, particularly Gibbs energy and equilibrium constants, regulate all reactions, a model rooted in the laws of thermodynamics is needed to accurately simulate cellular homeostasis and adaptation. The original target for confirming a working cellular and molecular biology model will focus on modeling mammalian cells during development and carcinogenesis induced by Ras. Ras signal transduction through Raf-MEK-Erk to induce elk-SRF transcription factor stimulation of early response genes such as fos was chosen due to the central role in development and cancer and the availability of data.