Phase Separation to Resolve Growth-Related Circuit Failures

Overview

Journal bioRxiv

Date 2024 Nov 18

PMID 39554057

Authors

Rong Zhang

Wangfei Yang

Rixin Zhang

Sadikshya Rijal

Abdelrahaman Youssef

Wenwei Zheng

Xiao-Jun Tian

Affiliations

Soon will be listed here.

Abstract

Fluctuations in host cell growth poses a significant challenge to synthetic gene circuits, often disrupting circuit function. Existing solutions typically rely on circuit redesign with alternative topologies or additional control elements, yet a broadly applicable approach remains elusive. Here, we introduce a new strategy based on liquid-liquid phase separation (LLPS) to stabilize circuit performance. By engineering a self-activating circuit with transcription factors (TF) fused to an intrinsically disordered region (IDR), we enable the formation of TF condensates at the promoter region, maintaining local TF concentration despite growth-mediated dilution. This condensate formation preserves bistable memory in the self-activating circuit, demonstrating that phase separation can robustly counteract growth fluctuations, offering a novel design principle for resilient synthetic circuits.

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