Evidence map›Paper›PMID 40315428›Full record

ArticleACS synthetic biology2025

Engineered Feedback Employing Natural Hypoxia-Responsive Factors Enhances Synthetic Hypoxia Biosensors.

Kathleen S Dreyer, Patrick S Donahue, Jonathan D Boucher, Katherine M Chambers, Marya Y Ornelas, Hailey I Edelstein, Benjamin D Leibowitz, Katherine J Zhu, Kate E Dray, Joseph J Muldoon and 1 more

Abstract read
In one paragraph

Article in ACS synthetic biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

11 authors.

Kathleen S DreyerDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, United States.ORCID 0000-0002-2041-4118
Patrick S DonahueDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, United States.
Jonathan D BoucherDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, United States.
Katherine M ChambersDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, United States.
Marya Y OrnelasDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, United States.
Hailey I EdelsteinDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, United States.
Benjamin D LeibowitzDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, United States.
Katherine J ZhuDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, United States.
Kate E DrayDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, United States.
Joseph J MuldoonDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, United States.ORCID 0000-0003-3784-3565
Joshua N LeonardDepartment of Chemical and Biological Engineering, Northwestern University, Evanston, Illinois 60208, United States.ORCID 0000-0003-4359-6126

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Devalingam Mahalingam · 1993 to 2026
$153.9M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008152 · NIGMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ARDEHALI, HOSSEIN · 1987 to 2021
$24.0M
Design-driven engineering of robust mammalian sense-and-respond functions: from parts to programsR01EB026510 · NIBIB · NORTHWESTERN UNIVERSITY · PI Neda Bagheri, Joshua Nathaniel Leonard · 2018 to 2026
$3.7M
NCI NIH HHS P30 CA060553NIBIB NIH HHS R01 EB026510NIGMS NIH HHS T32 GM008152
6 · The paper itself

Abstract

Inadequate oxygen supply is a feature of multiple acute and chronic diseases, and hypoxia biosensors can be deployed in engineered cells to study or treat disease. Although mediators of hypoxia-responsiveness have been characterized, dynamics of this response are less understood, and there is no general approach for tuning biosensor performance to meet application-specific needs. To address these gaps, we investigated the use of genetic circuits to enhance biosensor performance through feedback, ultimately achieving both low background and amplified hypoxia-induced gene expression. To build insight into the mechanisms by which our circuits modulate performance, we developed an explanatory mathematical model. Our analysis suggests a previously unreported dual regulatory mechanism in the natural hypoxia response, providing new insights into regulatory dynamics in chronic hypoxia. This study exemplifies the potential of using synthetic gene circuits to perturb natural systems in a manner that uniquely enables the elucidation of novel facets of natural regulation.

Indexed as

Biosensing TechniquesHypoxiaCell HypoxiaFeedback, PhysiologicalGene Regulatory NetworksOxygenSynthetic BiologyOxygenbiosensorgene circuithypoxiaODE modelssynthetic biology

Identifiers

PMID40315428
PMCPMC12949977

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.