NSF Award
0205061
EIA- 0205061<br/>Ray, Animesh <br/>Keck Graduate Institute <br/><br/>TITLE: A Twin-Framework To Analyze, Model and Design Robust, Complex Networks Using Biological and Computational Principles<br/><br/><br/><br/>Vulnerability of natural networks (such as the Internet, power supply grid, or gene regulatory circuits of cells) to accidental or deliberate attack is an important area of study. To date most work has focused on observations of existing static networks or on computer simulations, because most natural networks are difficult to manipulate experimentally. The complex molecular machinery regulating the synthesis of RNA molecules in the nucleus of budding yeast, a single-celled organism, is a real-world instance of a natural network that can be experimentally perturbed by defined genetic manipulations, and the results of these perturbations can be studied at the molecular level with unprecedented accuracy by current genomic techniques. The goal of this project is to develop a biology-driven computational framework for network robustness. To achieve this goal, a biological test-bed of sufficiently complexity, the gene regulatory network of sporulation in yeast, has been adopted as an experimental network model. Systematic gene knockout mutations (equivalent to node removal), and regulatory site deletion mutations (equivalent to edge removal), are being used as tools to actively alter the network. Effects of these perturbations in the gene regulatory network architecture are being analyzed at the level of whole-genome transcriptional profiles. A generic data model for large-scale networks is being developed. The relevant experimental behavior of the biological network is being emulated with the data model. Design principles underlying the architecture of complex networks selected through evolution are being probed through mathematical modeling and testing. Insights obtained from these studies will be valuable for defensive strategies in complex network design, with implications in, among others, communication technology, disaster response, and in designing robust communication infrastructure resistant to planned attacks.
