Understanding Signaling Dynamics Through Synthesis

Sci. Signal., 17 April 2012
Vol. 5, Issue 220, p. pe16
DOI: 10.1126/scisignal.2003092

Understanding Signaling Dynamics Through Synthesis

  1. Adrian L. Slusarczyk1 and
  2. Ron Weiss1,2,*
  1. 1Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  2. 2Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  1. *Corresponding author. E-mail: rweiss{at}mit.edu


Tissue-scale organization emerges from the action of sophisticated multiscale developmental programs. But the design rules for composing elementary signaling and information processing modules into such functional systems and for integrating them into the noisy and convoluted living context remain incompletely addressed. The construction of a synthetic gene circuit encoding contact-dependent signal propagation demonstrates one broadly applicable approach to this problem. The circuit comprises orthogonal signaling through the Delta ligand and the Notch receptor, multicellular positive feedback, and transcriptional signal amplification. Positive feedback and contact signaling proved sufficient for bistability and signal propagation across a population of mammalian cells, but only when combined with signal amplification. Thus, construction and characterization of synthetic gene circuits have made it possible to establish mechanistic sufficiency and the minimal requirements for the phenotype of interest.


A. L. Slusarczyk and R. Weiss, Understanding Signaling Dynamics Through Synthesis. Sci. Signal. 5, pe16 (2012).

Quantitative Analysis of Receptor Tyrosine Kinase-Effector Coupling at Functionally Relevant Stimulus Levels
S. Li, D. Bhave, J. M. Chow, T. V. Riera, S. Schlee, S. Rauch, M. Atanasova, R. L. Cate, and A. Whitty
J Biol Chem 290, 10018-10036 (17 April 2015)

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