Modeling a synthetic multicellular clock: Repressilators coupled by quorum sensing
Diverse biochemical rhythms are generated by thousands of cellular oscillators that somehow manage to operate synchronously. In fields ranging from circadian biology to endocrinology, it remains an exciting challenge to understand how collective rhythms emerge in multicellular structures. Using mathematical and computational modeling, we study the effect of coupling through intercell signaling in a population of Escherichia coli cells expressing a synthetic biological clock. Our results predict that a diverse and noisy community of such genetic oscillators interacting through a quorum-sensing mechanism should self-synchronize in a robust way, leading to a substantially improved global rhythmicity in the system. As such, the particular system of coupled genetic oscillators considered here might be a good candidate to provide the first quantitative example of a synchronization transition in a population of biological oscillators.
Additional Information© 2004 by the National Academy of Sciences. Edited by Charles S. Peskin, New York University, New York, NY, and approved June 7, 2004 (received for review October 31, 2003). J.G.-O. is partially supported by the National Science Foundation Integrative Graduate Education and Research Traineeship Program on Nonlinear Systems (Cornell University), Ministerio de Educacion, Cultura y Deportes (Spain) Grant PR2003-0253, and Ministerio de Ciencia y Tecnologıa (Spain) and Fonds Europeen de Developpement Regional (European Union) Projects BFM2002-04369 and BFM2003-07850. M.B.E. acknowledges generous support from the Burroughs–Wellcome Fund and the Seaver Institute. S.H.S. thanks the National Science Foundation for financial support. This paper was submitted directly (Track II) to the PNAS office.
Published - GARpnas04.pdf