Evidence map›Paper›PMID 41205601›Full record

ArticleCell2025

Phase separation to buffer growth-mediated dilution in synthetic circuits.

Rong Zhang, Wangfei Yang, Rixin Zhang, Amanda Godar, Sadikshya Rijal, Abdelrahaman Youssef, David R Nielsen, Wenwei Zheng, Xiao-Jun Tian

Abstract read
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
  2. Combinatorial decision-making driven by multicomponent surface condensates.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Programming Next-Generation Synthetic Biosensors by Genetic Circuit Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  5. Article
  6. Article
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Rong ZhangSchool of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85281, USA.
Wangfei YangCollege of Integrative Sciences and Arts, Arizona State University, Mesa, AZ 85212, USA.
Rixin ZhangSchool of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85281, USA.
Amanda GodarSchool of Life Sciences, Arizona State University, Tempe, AZ 85281, USA.
Sadikshya RijalSchool of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85281, USA.
Abdelrahaman YoussefSchool of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85281, USA.
David R NielsenSchool for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, AZ 85281, USA.
Wenwei ZhengCollege of Integrative Sciences and Arts, Arizona State University, Mesa, AZ 85212, USA.
Xiao-Jun TianSchool of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ 85281, USA. Electronic address: xiaojun.tian@asu.edu.

Funding

Multi-Scale Engineering of Heterogeneity in the Host-Aware Synthetic Gene CircuitsR35GM142896 · NIGMS · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI TIAN, XIAOJUN · 2021 to 2025
$2.0M
Decoding the mechanism of disordered protein interactionsR35GM146814 · NIGMS · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · PI Wenwei Zheng · 2022 to 2026
$1.8M
NIGMS NIH HHS R35 GM142896NIGMS NIH HHS R35 GM146814
6 · The paper itself

Abstract

Fluctuations in host cell growth pose a critical challenge for maintaining reliable function in synthetic gene circuits. Growth-mediated dilution causes a global reduction in circuit component concentrations, which can significantly destabilize circuit behavior. However, effective strategies to counteract this problem remain lacking. Here, we present a phase-separation-based strategy to directly mitigate dilution effects. By fusing transcription factors (TFs) to intrinsically disordered regions (IDRs), we drive the formation of transcriptional condensates that concentrate TFs at their target promoters. These condensates buffer against prolonged rapid dilution of TF concentration and preserve bistable memory in self-activation circuits across variable growth conditions. We further show that this approach improves production efficiency in a cinnamic acid biosynthesis pathway. Together, our results establish liquid-liquid phase separation as an emerging design principle for constructing resilient synthetic circuits that maintain robust performance under dynamic growth conditions.

Indexed as

Gene Regulatory NetworksSynthetic BiologyCinnamatesEscherichia coliPhase SeparationPromoter Regions, GeneticTranscription FactorsCinnamatescinnamic acidTranscription Factorsbuffering capacitycircuit memory retentioncircuit robustnesscondensate-promoter co-localizationgene circuit stabilityspatial control of gene expressionsynthetic biologysynthetic condensatesynthetic gene circuit

Identifiers

PMID41205601
PMCPMC12616627

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.