Controlling spatiotemporal pattern formation in a concentration gradient with a synthetic toggle switch.

Molecular Systems Biology
Içvara BarbierYolanda Schaerli

Abstract

The formation of spatiotemporal patterns of gene expression is frequently guided by gradients of diffusible signaling molecules. The toggle switch subnetwork, composed of two cross-repressing transcription factors, is a common component of gene regulatory networks in charge of patterning, converting the continuous information provided by the gradient into discrete abutting stripes of gene expression. We present a synthetic biology framework to understand and characterize the spatiotemporal patterning properties of the toggle switch. To this end, we built a synthetic toggle switch controllable by diffusible molecules in Escherichia coli. We analyzed the patterning capabilities of the circuit by combining quantitative measurements with a mathematical reconstruction of the underlying dynamical system. The toggle switch can produce robust patterns with sharp boundaries, governed by bistability and hysteresis. We further demonstrate how the hysteresis, position, timing, and precision of the boundary can be controlled, highlighting the dynamical flexibility of the circuit.

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Citations

Sep 24, 2020·Biochemical Society Transactions·Javier Santos-Moreno, Yolanda Schaerli
Mar 7, 2021·Biomimetics·Diego Navarro-MateuPedro Cortes Nieves
May 11, 2021·Trends in Microbiology·Nicolas E GrandelMatthew R Bennett
Mar 18, 2021·Physical Biology·Souvadra HatiMohit Kumar Jolly
Jun 1, 2021·Interface Focus·Erik Clark
Jul 24, 2021·Integrative and Comparative Biology·A Michelle LawingDerek Wright
Nov 30, 2021·Microbial Biotechnology·Martina Oliver HuidobroMark Isalan

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Methods Mentioned

BETA
flow cytometry
PCRs

Software Mentioned

SBOL
FlowJo
R
PyDREAM
Fiji ImageJ
ImageJ
IPTG

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