Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Optogenetic control of the integrated stress response reveals proportional encoding and the stress memory landscape

View ORCID ProfileTaivan Batjargal, View ORCID ProfileFrancesca Zappa, Ryan J Grant, View ORCID ProfileRobert A Piscopio, View ORCID ProfileAlex Chialastri, View ORCID ProfileSiddharth S Dey, View ORCID ProfileDiego Acosta-Alvear, View ORCID ProfileMaxwell Z Wilson
doi: https://doi.org/10.1101/2022.05.24.493309
Taivan Batjargal
2Biomolecular Science and Engineering Program, University of California Santa Barbara
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Taivan Batjargal
Francesca Zappa
3Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara
6Altos Labs Bay Area Institute of Science, Altos Labs, Inc.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Francesca Zappa
Ryan J Grant
3Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert A Piscopio
3Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Robert A Piscopio
Alex Chialastri
5Department of Chemical Engineering, University of California Santa Barbara
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Alex Chialastri
Siddharth S Dey
1Center for BioEngineering, University of California Santa Barbara
4Neuroscience Research Institute, University of California Santa Barbara
5Department of Chemical Engineering, University of California Santa Barbara
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Siddharth S Dey
Diego Acosta-Alvear
2Biomolecular Science and Engineering Program, University of California Santa Barbara
3Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara
4Neuroscience Research Institute, University of California Santa Barbara
6Altos Labs Bay Area Institute of Science, Altos Labs, Inc.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Diego Acosta-Alvear
  • For correspondence: daa@lifesci.ucsb.edu mzw@ucsb.edu
Maxwell Z Wilson
1Center for BioEngineering, University of California Santa Barbara
2Biomolecular Science and Engineering Program, University of California Santa Barbara
3Department of Molecular, Cellular, and Developmental Biology, University of California Santa Barbara
4Neuroscience Research Institute, University of California Santa Barbara
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Maxwell Z Wilson
  • For correspondence: daa@lifesci.ucsb.edu mzw@ucsb.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

The Integrated Stress Response (ISR) is a conserved signaling network that detects cellular damage and computes adaptive or terminal outcomes. Understanding the mechanisms that underly these computations has been difficult because natural stress inputs activate multiple parallel signaling pathways and classical ISR inducers have pleiotropic effects. To overcome this challenge, we engineered photo-switchable control over the ISR stress sensor kinase PKR (opto-PKR), which allows virtual control of the ISR. Using controlled light inputs to activate opto-PKR we traced information flow in the ISR both globally, in the transcriptome, and for key ISR effectors. Our analyses revealed a biphasic, input-proportional transcriptional response with two dynamic modes, transient and gradual, that correspond to adaptive and terminal ISR outcomes. Using this data, we constructed an ordinary differential equation (ODE) model of the ISR which predicted system hysteresis dependent on prior stress durations and that stress memory encoding may lead to resilience. Our results demonstrate that the input dynamics of the ISR encode information in stress levels, durations, and the timing between stress encounters.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted May 25, 2022.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Optogenetic control of the integrated stress response reveals proportional encoding and the stress memory landscape
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Optogenetic control of the integrated stress response reveals proportional encoding and the stress memory landscape
Taivan Batjargal, Francesca Zappa, Ryan J Grant, Robert A Piscopio, Alex Chialastri, Siddharth S Dey, Diego Acosta-Alvear, Maxwell Z Wilson
bioRxiv 2022.05.24.493309; doi: https://doi.org/10.1101/2022.05.24.493309
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Optogenetic control of the integrated stress response reveals proportional encoding and the stress memory landscape
Taivan Batjargal, Francesca Zappa, Ryan J Grant, Robert A Piscopio, Alex Chialastri, Siddharth S Dey, Diego Acosta-Alvear, Maxwell Z Wilson
bioRxiv 2022.05.24.493309; doi: https://doi.org/10.1101/2022.05.24.493309

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Systems Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4654)
  • Biochemistry (10298)
  • Bioengineering (7614)
  • Bioinformatics (26189)
  • Biophysics (13444)
  • Cancer Biology (10620)
  • Cell Biology (15333)
  • Clinical Trials (138)
  • Developmental Biology (8451)
  • Ecology (12753)
  • Epidemiology (2067)
  • Evolutionary Biology (16760)
  • Genetics (11356)
  • Genomics (15399)
  • Immunology (10548)
  • Microbiology (25040)
  • Molecular Biology (10151)
  • Neuroscience (54086)
  • Paleontology (398)
  • Pathology (1655)
  • Pharmacology and Toxicology (2877)
  • Physiology (4314)
  • Plant Biology (9196)
  • Scientific Communication and Education (1579)
  • Synthetic Biology (2541)
  • Systems Biology (6752)
  • Zoology (1452)