Tunability and Noise Dependence in Differentiation Dynamics
The dynamic process of differentiation depends on the architecture, quantitative parameters, and noise of underlying genetic circuits. However, it remains unclear how these elements combine to control cellular behavior. We analyzed the probabilistic and transient differentiation of Bacillus subtilis cells into the state of competence. A few key parameters independently tuned the frequency of initiation and the duration of competence episodes and allowed the circuit to access different dynamic regimes, including oscillation. Altering circuit architecture showed that the duration of competence events can be made more precise. We used an experimental method to reduce global cellular noise and showed that noise levels are correlated with frequency of differentiation events. Together, the data reveal a noise-dependent circuit that is remarkably resilient and tunable in terms of its dynamic behavior.
Additional Information© 2007 American Association for the Advancement of Science. Received 13 November 2006; accepted 26 February 2007. We thank R. Kishony, B. Shraiman, U. Alon, R. Ranganathan, S. Altschuler, L. Wu, and K. Süel, together with members of the Elowitz laboratory, for thoughtful comments and discussions. This work was supported by grants from NIH (R01 GM079771 to M.B.E. and GM068763 to the Center for Modular Biology), the Searle Scholars Program, the Human Frontiers Science Program, and the Packard Foundation. G.M.S. is supported by California Institute of Technology Center for Biological Circuit Design and the University of Texas Southwestern's Endowed Scholars Program. J.G.O. acknowledges financial support from the Ministerio de Educacion y Ciencia (Spain, project FIS2006-11452) and from the Generalitat de Catalunya.
Supplemental Material - Suel_SOM.pdf