Journal
MOLECULAR SYSTEMS BIOLOGY
Volume 7, Issue -, Pages -Publisher
WILEY
DOI: 10.1038/msb.2011.13
Keywords
cell signaling; design principles; feedback; switch-like response; synthetic biology
Categories
Funding
- American Heart Association [0835132N]
- National Science Foundation [1055231]
- University of Pennsylvania
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1055231] Funding Source: National Science Foundation
Ask authors/readers for more resources
The ability to engineer an all-or-none cellular response to a given signaling ligand is important in applications ranging from biosensing to tissue engineering. However, synthetic gene network 'switches' have been limited in their applicability and tunability due to their reliance on specific components to function. Here, we present a strategy for reversible switch design that instead relies only on a robust, easily constructed network topology with two positive feedback loops and we apply the method to create highly ultrasensitive (n(H)>20), bistable cellular responses to a synthetic ligand/receptor complex. Independent modulation of the two feedback strengths enables rational tuning and some decoupling of steady-state (ultrasensitivity, signal amplitude, switching threshold, and bistability) and kinetic (rates of system activation and deactivation) response properties. Our integrated computational and synthetic biology approach elucidates design rules for building cellular switches with desired properties, which may be of utility in engineering signal-transduction pathways. Molecular Systems Biology 7: 480; published online 29 March 2011; doi:10.1038/msb.2011.13
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available