Work

Synthetic conversion of a graded receptor signal into a tunable, reversible switch

Year: 2011

Type: article

Abstract: 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.

Source: Molecular Systems Biology

DOI: 10.1038/msb.2011.13

Authors: Santhosh Palani, Casim A Sarkar

Institution: University of Pennsylvania

Language: English

Topic: Gene Regulatory Network Analysis

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $7,990

Funders: National Science Foundation, American Heart Association, University of Pennsylvania