Inferring feedback regulation from static snapshots of a single signal

Ginzberg M, Tan C, Patel N, Kafri R · 2026 · Biochemistry and Biophysics Reports · Atlas ID GIN2026

What this study shows

Introduces AoF (Assay of Feedback), a perturbation-free single-cell imaging method that reconstructs how a signal CHANGES OVER TIME from fixed-cell snapshots, using DNA content and Geminin to order cells along the cell cycle. Applied to Akt phosphorylation, it uncovers a negative feedback loop that is active only in a narrow window at the G1/S transition; biochemistry points to mTORC1/S6K1-dependent inhibitory phosphorylation of IRS1 as the likely source, though the authors state this edge is not uniquely established. Directly relevant to the question of whether mTOR pathway activity is better described as a time-varying pattern than a fixed level.

Abstract

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Direct measurement of feedback regulation remains difficult because it usually relies on pathway perturbations and prior knowledge of circuit topology. We introduce AoF (Assay of Feedback), a single-cell imaging framework that combines fixed-cell measurements of a target (together with DNA and Geminin as cell-cycle ordering markers) with ergodic rate analysis to reconstruct target dynamics in steady-state proliferating populations and quantify how a target's inferred rate of change depends on its own level.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human/mammalian cultured cells (fixed-cell single-cell imaging, ergodic rate analysis)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Human/mammalian cultured cells (fixed-cell single-cell imaging, ergodic rate analysis)
Journal	Biochemistry and Biophysics Reports
Year	2026
Peer reviewed	Yes
Record last updated	2026-08-22
Source	DOI 10.1016/j.bbrep.2026.102747 · PMID 42643853 · Free full text (PMC13505498)

Extracted findings

Intervention	None (observational imaging assay); mTORC1/S6K1 inhibition used in supporting biochemistry
Target	AKT phosphorylation; mTORC1-S6K1-IRS1 negative feedback
Model	Cultured mammalian cells
Effect	Reveals cell-cycle-localized negative feedback on AKT at G1/S, attributed to mTORC1/S6K1-IRS1

Cite this paper

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Ginzberg, M., Tan, C., Patel, N., & Kafri, R. (2026). Inferring feedback regulation from static snapshots of a single signal. Biochemistry and Biophysics Reports. https://doi.org/10.1016/j.bbrep.2026.102747

@article{GIN2026,
  author       = {Ginzberg, M. and Tan, C. and Patel, N. and Kafri, R.},
  title        = {{Inferring feedback regulation from static snapshots of a single signal}},
  journal      = {Biochemistry and Biophysics Reports},
  year         = {2026},
  doi          = {10.1016/j.bbrep.2026.102747},
  note         = {PMID: 42643853},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record GIN2026) [Data set]. https://mtor-atlas.org/study/GIN2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_GIN2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record GIN2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/GIN2026/},
  doi          = {10.5281/zenodo.22059963}
}