OPTIMAL PERFORMANCE OF THE HEAT-SHOCK GENE REGULATORY NETWORK 1

Abstract: In this work, we study the optimality principles in the heat shock response, a cellular response of utmost physiological importance. The heat shock response refers to the mechanism by which organisms react to a sudden increase in the ambient temperature. The consequence of such an unmediated temperature increase at the cellular level is the unfolding, misfolding, or aggregation of cell proteins, which threatens the life of the cell. This increase in damaged proteins is usually counteracted by a simultaneous increase in the level of heat tolerant proteins, known as chaperones and proteases, which either refold or degrade unfolded proteins. These heat shock proteins are necessary for protein folding. Their production, however, is metabolically costly and the benefits should be constantly balanced with the cost. Building on a heat shock model we have developed in previous work (El-Samad et al., 2004), we investigate how the heat shock response balances the two conflicting performance objectives of achieving low levels of heat shock and unfolded proteins. Specifically, we formulate and solve a multi-objective optimization problem where both the cost of producing and maintaining HSPs and the cost of unfolded proteins are considered as optimization criteria