The Dynamical Logic of Developmental Regulatory Networks

Duke University, Durham NC

Investigators

Abstract

During development of a living organism, the production of the necessary proteins for specifying cell fates is governed by a network of interacting genes. Mathematical models of these networks are necessary both for generating useful hypotheses for further experimentation. This project addresses the question of what form such models should take, focusing on the paradigmatic case of the early stages of development of the sea urchin embryo. The working hypothesis is that continuous-time Boolean models can efficiently account for three crucial features: the structure of the network, the logic carried out by each element, and the timing of activation events. The models allow the syntheses of results from multiple experiments and checks for consistency of interpretation, and reveals architectural features required for complex networks to perform given tasks. A major goal of the project is to construct a network model, including inter-cell signaling, that accounts for the experimentally observed gene activity involved in creating the distinct tissues first formed in sea urchin embryos. Understanding the mechanisms that determine what types of cells will be produced at different locations is central to the grand challenge of treating or preventing cancer as well as the science of embryonic development. The mathematical modeling issues addressed in this project may find additional application in other systems in which independent agents sharply switch behaviors based on time--delayed information generated by other agents, such as neuroscience and traffic control. The project directly provides training for graduate students in the rapidly emerging field of systems biology, where academic and industrial advances require a combination of mathematical and biological expertise.