Simulation modeling framework to study transcriptional regulation through the dynamic changes in the configuration of DNA binding factors, A

Abstract

Transcriptional regulation is the complex system behavior arising from the interaction of numerous regulators with the DNA. The DNA sequence contains the information for this complex system to produce precise gene expression at specific times and cellular locations. Despite the tremendous progress in understanding the behaviors of individual components, we are unable to predict transcriptional behavior from the signal encoded in a DNA sequence. To better understand transcriptional regulation, we need to construct interpretable, quantitative models of the regulation processes derived from fundamental biological principles. Models need to capture the mechanisms of the individual components and the interactions between components, including the transcriptional machinery itself. Models should be capable of capturing the regulation signal found in any DNA sequence and allow interrogation of the interactions that lead to transcription events. I have developed modeling frameworks that capture the behavior of individual components, the competition between components for interactions with the DNA, and more importantly, the dynamics of regulatory events occurring within individual cells. I can construct biologically realistic computational models that capture the inherent stochasticity and dynamics of regulatory interactions in simulations and visualize the results of configuration changes occurring in the components bound to the DNA.