A unified design space of synthetic stripe-forming networks

TLDR

Synthetic biology enables the study of gene regulatory networks, yet most gene circuits with predefined behaviours are engineered on a case‑by‑case basis. The authors aim to computationally and experimentally explore the full design space of 3‑node stripe‑forming networks. They computationally screened every possible 3‑node network for stripe formation in a morphogen gradient and then synthetically built four minimal networks guided by engineering criteria, demonstrating four distinct mechanisms. Four distinct dynamical mechanisms were identified, experimentally validated, and used to construct a minimal 2‑node archetype network that captures the explored design space.

Abstract

Synthetic biology is a promising tool to study the function and properties of gene regulatory networks. Gene circuits with predefined behaviours have been successfully built and modelled, but largely on a case-by-case basis. Here we go beyond individual networks and explore both computationally and synthetically the design space of possible dynamical mechanisms for 3-node stripe-forming networks. First, we computationally test every possible 3-node network for stripe formation in a morphogen gradient. We discover four different dynamical mechanisms to form a stripe and identify the minimal network of each group. Next, with the help of newly established engineering criteria we build these four networks synthetically and show that they indeed operate with four fundamentally distinct mechanisms. Finally, this close match between theory and experiment allows us to infer and subsequently build a 2-node network that represents the archetype of the explored design space. Constructing gene circuits with predefined behaviours is typically done on a case-by-case basis. Schaerli et al.instead computationally explore the design space for 3-node networks that generate a stripe in response to a morphogen gradient, and build networks based on their simplest possible forms.