Evidence map›Paper›PMID 35176859›Full record

ArticleACS synthetic biology2022

Natural and Designed Proteins Inspired by Extremotolerant Organisms Can Form Condensates and Attenuate Apoptosis in Human Cells.

Mike T Veling, Dan T Nguyen, Nicole N Thadani, Michela E Oster, Nathan J Rollins, Kelly P Brock, Neville P Bethel, Samuel Lim, David Baker, Jeffrey C Way and 3 more

Open access · greenAbstract read
In one paragraph

Article in ACS synthetic biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
10.0field-weighted citation impact, top 2% of its field
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

16 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Article
  3. Fibril Structure of Desiccation-Protective Tardigrade Protein CAHS-8.Angewandte Chemie (International ed. in English) · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Biomolecular condensates-Prerequisites for anhydrobiosis?Protein science : a publication of the Protein Society · 2025
    Review
  9. Review
  10. Crowding in Anhydrobiosis.Sub-cellular biochemistry · 2025
    Review
  11. Article
  12. Article
  13. Reply to Tanaka and Kunieda: Control protein GFP also shows a mesh-like structure in desiccating tardigrade cells.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  14. In vivo expression vector derived from anhydrobiotic tardigrade genome enables live imaging in Eutardigrada.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  15. Review
  16. 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

13 authors at 5 institutions in 1 country.

Mike T VelingDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.ORCID 0000-0003-0197-8302
Dan T NguyenDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.ORCID 0000-0001-8198-9401
Nicole N ThadaniDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.
Michela E OsterDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.ORCID 0000-0001-9556-018X
Nathan J RollinsDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.
Kelly P BrockDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.
Neville P BethelInstitute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Samuel LimDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.
David BakerInstitute for Protein Design, University of Washington, Seattle, Washington 98195, United States.
Jeffrey C WayDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.
Debora S MarksDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.
Roger L ChangDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.
Pamela A SilverDepartment of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.ORCID 0000-0002-7856-4071
Harvard University · USAlbert Einstein College of Medicine · USBroad Institute · USHoward Hughes Medical Institute · USUniversity of Washington · US

Funding

Systems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI SORGER, PETER KARL · 2018 to 2022
$10.8M
Howard Hughes Medical Institute GT11817NCI NIH HHS U54 CA225088
6 · The paper itself

Abstract

Many organisms can survive extreme conditions and successfully recover to normal life. This extremotolerant behavior has been attributed in part to repetitive, amphipathic, and intrinsically disordered proteins that are upregulated in the protected state. Here, we assemble a library of approximately 300 naturally occurring and designed extremotolerance-associated proteins to assess their ability to protect human cells from chemically induced apoptosis. We show that several proteins from tardigrades, nematodes, and the Chinese giant salamander are apoptosis-protective. Notably, we identify a region of the human ApoE protein with similarity to extremotolerance-associated proteins that also protects against apoptosis. This region mirrors the phase separation behavior seen with such proteins, like the tardigrade protein CAHS2. Moreover, we identify a synthetic protein, DHR81, that shares this combination of elevated phase separation propensity and apoptosis protection. Finally, we demonstrate that driving protective proteins into the condensate state increases apoptosis protection, and highlights the ability of DHR81 condensates to sequester caspase-7. Taken together, this work draws a link between extremotolerance-associated proteins, condensate formation, and designing human cellular protection.

Indexed as

Intrinsically Disordered ProteinsTardigradaAnimalsApoptosisHumansIntrinsically Disordered Proteinsapoptosisintrinsically disordered proteinsphase separationstress tolerance

Identifiers

PMID35176859
PMCPMC9651988
OpenAlexW4220971899

What OpenQuestion holds

Textmetadata
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Read underepoch 390

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.