QSB: Computational and Experimental Studies of Pathways in Yeast

The long range goal of this project is to investigate a framework that can improve understanding of the topology/connectivity of complex biological pathways. This research combines experimental molecular genetics with computational systems biology to develop new approaches for mapping complex signal transduction pathways in eukaryotic cells. The initial system for study is the Ras and Tor pathways in the budding yeast Saccharomyces cerevisiae. The research will employ data sets from whole genome expression analysis to develop and validate the pathway map. The research will focus on three avenues of analysis with the objectives: (1) to study a genetic epistasis analysis approach using extensive DNA microarray data to define a qualitative connectivity map of the pathways, (2) investigate a new computational systems approach based on a superstructure representation and a mixed integer linear optimization framework for the prediction of the topology of the complex pathways, and (3) study a quantitative analysis framework for the effect of model uncertainty on the network topology of the metabolic pathways.