Next-generation quantitative measurements to validate a model for yeast nitrogen catabolite repression in Saccharomyces cerevisiae
Boczko, Erik M.
Our work is motivated by the desire to quantitatively measure biological dynamical systems. Our agenda is to describe and understand emergent behavior and to explain the observed super robustness of biological dynamics. The specific system that provides the focus for our work is an ostensibly simple stress response circuit in baker's yeast, Saccharomyces cerevisiae, that regulates the organisms' genetic response to nitrogen limitation called nitrogen catabolite repression (NCR). The circuitry of the network has been well studied for the last 40 years and comparatively much is known about its function, however, little is known about its dynamics. In order to study the dynamics at the same level of sophistication at which we formulate and reason with mathematical models, we require quantitative biophysical and biochemical techniques that are accurate at molecular dimensions on physiological timescales. Such techniques are currently in their infancy. The overall goal is to further develop the tools and techniques to measure the quantitative biological behavior of the NCR circuit well enough to refine a current NCR model and understand how to apply the model to other regulatory networks leading to advances in biology, control theory and beyond. The broader impact of our effort reaches far beyond understanding the molecular physiology of a simple fungal stress response towards a deeper understanding of the underpinnings of why some circuits persist while others do not.