TY - JOUR T1 - A new motif for robust perfect adaptation in noisy biomolecular networks JF - bioRxiv DO - 10.1101/024919 SP - 024919 AU - Corentin Briat AU - Ankit Gupta AU - Mustafa Khammash Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/08/17/024919.abstract N2 - Homeostasis is a running theme in biology. Often achieved through feedback regulation strategies, homeostasis allows living cells to control their internal environment as a means for surviving changing and unfavourable environments. While many endogenous homeostatic motifs have been studied in living cells, synthetic homeostatic circuits have received far less attention. The tight regulation of the abundance of cellular products and intermediates in the noisy environment of the cell is now recognised as a critical requirement for several biotechnology and therapeutic applications. Here we lay the foundation for a regulation theory at the molecular level that explicitly takes into account the noisy nature of biochemical reactions and provides novel tools for the analysis and design of robust synthetic homeostatic circuits. Using these ideas, we propose a new regulation motif that implements an integral feedback strategy which can generically and effectively regulate a wide class of reaction networks. By combining tools from probability and control theory, we show that the proposed control motif preserves the stability of the overall network, steers the population of any regulated species to a desired set point, and achieves robust perfect adaptation – all without any prior knowledge of reaction rates. Moreover, our proposed control motif can be implemented using a very small number of molecules and hence has a negligible metabolic load. Strikingly, the regulatory motif exploits stochastic noise, leading to enhanced regulation in scenarios where noise-free implementations result in dysregulation. Several examples demonstrate the potential of the approach. ER -