Feedback Regulation of the Heat Shock Response in E. coli

Abstract

Systems Biology is an emerging new field defined as the study of biology as an integrated system of components that act interdependently to accomplish certain functions. This approach holds the promise of offering precious insight into aspects of biological organization that cannot be identified through a reductionist approach concerned solely with the study of individual molecules. In this work, we illustrate this viewpoint through the example of the bacterial heat shock response. The heat shock response is an important mechanism that combats harmful effects of an unmediated increase in temperature. Such an increase in temperature causes the unfolding or aggregation of the cellular proteins, which imposes a tremendous amount of stress on the cell. The heat shock response is implemented through an elaborate system of controls whose purpose is to refold denatured proteins, therefore restoring their normal function. In this paper, we present a deterministic model for the heat shock response. We use this model to gain insight into the design and performance objectives of this response. We then provide a stochastic treatment based on the Stochastic Simulation Algorithm of Gillepsie [18]. This stochastic investigation validates the use of the deterministic approach in modeling the heat shock response, and motivates the investigation of feedback structures that play a role in attenuating stochastic fluctuations.