Sequestration‐based bistability enables tuning of the switching boundaries and design of a latch

Molecular Systems Biology

David Chen¹ 

[1] The UC Berkeley-UCSF Graduate Program in Bioengineering, Berkeley, CA, USA

关键词: bistability;    genetic circuits;    nonlinear dynamics;    sequestration;    synthetic biology;   

DOI  :  10.1038/msb.2012.52

来源: Wiley

【 摘 要 】

Abstract

Natural biological systems have evolved a diverse array of switches to realize their strategies for environmental response and development. Emerging applications of synthetic biology have begun to exploit such switches to achieve increasingly sophisticated designed behaviors. However, not all switch architectures allow facile design of the switching and memory properties. Furthermore, not all designs are built from components for which large families of variants exist, a requirement for building many orthogonal switch variants. Therefore, there is a critical need from genetic engineers for scalable strategies that yield custom bistable switches. Here, we use a sigma factor and its cognate anti-sigma factor to experimentally verify that ultrasensitivity from sequestration combined with positive feedback is sufficient to build a bistable switch. We show that sequestration allows us to predictably tune the switching boundaries, and we can easily tune our switch to function as a set–reset latch that can be toggled between two states by a pulse of inducer input.

Synopsis

Engineering of the sigma/anti-sigma system in Escherichia coli shows that sequestration combined with positive feedback can be used to build a bistable memory device. The minimal requirement of this design makes it potentially scalable and generalizable.

• A sigma factor and its cognate anti-sigma factor are used to build a bistable switch without relying on cooperativity.
• The switching boundaries are tunable and allow rapid design of a set-reset latch.
• This design is analytically tractable and should be scalable to more sigma/anti-sigma pairs.

【 授权许可】

CC BY-NC-SA   
Copyright © 2012 EMBO and Macmillan Publishers Limited

Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.