Evidence map›Paper›PMID 31269201›Full record

ArticleNucleic acids research2019

Noise-reducing optogenetic negative-feedback gene circuits in human cells.

Michael Tyler Guinn, Gábor Balázsi

Abstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing 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

24 citing papers in PubMed.

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  18. Article
  19. Light Control of Gene Expression Dynamics.Advances in experimental medicine and biology · 2021
    Review
  20. 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

2 authors.

Michael Tyler GuinnBiomedical Engineering Department, Stony Brook University, Stony Brook, NY 11794, USA.
Gábor BalázsiBiomedical Engineering Department, Stony Brook University, Stony Brook, NY 11794, USA.

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM008444 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI FROHMAN, MICHAEL A. · 1992 to 2024
$12.6M
Dynamics and evolution of synthetic and natural gene regulatory networksR35GM122561 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI BALAZSI, GABOR · 2017 to 2025
$4.2M
NIGMS NIH HHS R35 GM122561NIGMS NIH HHS T32 GM008444
6 · The paper itself

Abstract

Gene autorepression is widely present in nature and is also employed in synthetic biology, partly to reduce gene expression noise in cells. Optogenetic systems have recently been developed for controlling gene expression levels in mammalian cells, but most have utilized activator-based proteins, neglecting negative feedback except for in silico control. Here, we engineer optogenetic gene circuits into mammalian cells to achieve noise-reduction for precise gene expression control by genetic, in vitro negative feedback. We build a toolset of these noise-reducing Light-Inducible Tuner (LITer) gene circuits using the TetR repressor fused with a Tet-inhibiting peptide (TIP) or a degradation tag through the light-sensitive LOV2 protein domain. These LITers provide a range of nearly 4-fold gene expression control and up to 5-fold noise reduction from existing optogenetic systems. Moreover, we use the LITer gene circuit architecture to control gene expression of the cancer oncogene KRAS(G12V) and study its downstream effects through phospho-ERK levels and cellular proliferation. Overall, these novel LITer optogenetic platforms should enable precise spatiotemporal perturbations for studying multicellular phenotypes in developmental biology, oncology and other biomedical fields of research.

Indexed as

Feedback, PhysiologicalAlgorithmsAnimalsCells, CulturedGene Expression RegulationGene Regulatory NetworksHEK293 CellsHumansLightModels, GeneticOptogeneticsProto-Oncogene Proteins p21(ras)Reproducibility of ResultsSynthetic BiologyKRAS protein, humanProto-Oncogene Proteins p21(ras)

Identifiers

PMID31269201
PMCPMC6698750

What OpenQuestion holds

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Registered trials

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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.