Evidence map›Paper›PMID 29483642›Full record

ArticleNature chemical biology2018

A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters.

Kiryl D Piatkevich, Erica E Jung, Christoph Straub, Changyang Linghu, Demian Park, Ho-Jun Suk, Daniel R Hochbaum, Daniel Goodwin, Eftychios Pnevmatikakis, Nikita Pak and 17 more

Erratum issuedAbstract read
In one paragraph

Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 201 papers.

0numbers the graph read from it
0cells of the map it votes in
201citing papers in PubMed
21.8field-weighted citation impact, top 1% 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

201 citing papers in PubMed, 345 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  11. Cancer: A bioelectric disease?Clinical and translational medicine · 2026
    Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

141 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 10 institutions in 3 countries.

Kiryl D PiatkevichMedia Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Erica E JungMedia Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Christoph StraubHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Changyang LinghuMedia Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Demian ParkMedia Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Ho-Jun SukMedia Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Daniel R HochbaumHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-6220-6651
Daniel GoodwinMedia Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Eftychios PnevmatikakisSimons Center Data Analysis, Simons Foundation, New York, NY, USA.ORCID 0000-0003-1509-6394
Nikita PakMedia Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Takashi KawashimaJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA.
Chao-Tsung YangJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA.
Jeffrey L RhoadesPicower Institute for Learning & Memory and Department of Brain & Cognitive Sciences, MIT, Cambridge, MA, USA.ORCID 0000-0001-5077-2533
Or ShemeshMedia Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Shoh AsanoMedia Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
Young-Gyu YoonMedia Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.ORCID 0000-0002-5660-049X
Limor FreifeldMedia Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.ORCID 0000-0002-0739-6947
Jessica L SaulnierHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA, USA.
Clemens RieglerDepartment of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA, USA.
Florian EngertDepartment of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, MA, USA.
Thom HughesDepartment of Cell Biology and Neuroscience, Montana State University, Bozeman, Montana, USA.ORCID 0000-0002-8430-070X
Mikhail DrobizhevDepartment of Cell Biology and Neuroscience, Montana State University, Bozeman, Montana, USA.
Balint SzaboDepartment of Biological Physics, Eotvos University, Budapest, Hungary.
Misha B AhrensJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA.
Steven W FlavellPicower Institute for Learning & Memory and Department of Brain & Cognitive Sciences, MIT, Cambridge, MA, USA.
Bernardo L SabatiniHoward Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0095-9177
Edward S BoydenMedia Lab, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA. esb@media.mit.edu.
Howard Hughes Medical Institute · USMassachusetts Institute of Technology · USIIT@MIT · USMontana State University · USEötvös Loránd University · HUHarvard–MIT Division of Health Sciences and Technology · USHarvard University · USMcGovern Institute for Brain Research · USSimons Foundation · USUniversity of Vienna · AT

Funding

Recording neural activities onto DNAR01MH103910 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI BOYDEN, EDWARD S., CHURCH, GEORGE M · 2013 to 2017
$9.5M
Novel Platforms for Systematic Optical Control of Complex Neural Circuits In VivoR01DA029639 · NIDA · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2010 to 2023
$6.7M
Redesigning General Anesthesia (Admin Supp)R01GM104948 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S., BROWN, EMERY N · 2012 to 2016
$4.4M
High-throughput robotic analysis of integrated neuronal phenotypesR01EY023173 · NEI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S., FOREST, CRAIG · 2012 to 2016
$4.3M
Millisecond-Timescale Whole-Brain Neural Activity Mapping in Health and DiseaseDP1NS087724 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BOYDEN, EDWARD S. · 2013 to 2017
$3.9M
New approaches for better protein voltage sensorsU01NS099691 · NINDS · YALE UNIVERSITY · PI COHEN, LAWRENCE B · 2016 to 2018
$2.1M
Neuromodulatory control of collective circuit dynamics in C. elegansR01NS104892 · NINDS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI FLAVELL, STEVEN WILLEM · 2017 to 2021
$2.1M
Vascular Interfaces for Brain Imaging and StimulationR24MH106075 · NIMH · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI DESIMONE, ROBERT · 2014 to 2016
$1.4M
Causal Analysis of Electrically Connected Neural NetworksR01NS087950 · NINDS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI HAN, XUE · 2013 to 2016
$1.3M
High Speed, Multi-sensor Light Field Deconvolution Microscopy for Whole Brain Recording of Neuronal ActivityR43MH109332 · NIMH · LEAFLABS, LLC · PI BOYDEN, EDWARD S., SHERWOOD, JOHN L · 2016 to 2017
$892k
NEI NIH HHS R01 EY023173NIDA NIH HHS R01 DA029639NIGMS NIH HHS R01 GM104948NIMH NIH HHS R01 MH103910NIMH NIH HHS R24 MH106075NIMH NIH HHS R43 MH109332NINDS NIH HHS DP1 NS087724NINDS NIH HHS R01 NS087950NINDS NIH HHS R01 NS104892NINDS NIH HHS U01 NS099691
6 · The paper itself

Abstract

We developed a new way to engineer complex proteins toward multidimensional specifications using a simple, yet scalable, directed evolution strategy. By robotically picking mammalian cells that were identified, under a microscope, as expressing proteins that simultaneously exhibit several specific properties, we can screen hundreds of thousands of proteins in a library in just a few hours, evaluating each along multiple performance axes. To demonstrate the power of this approach, we created a genetically encoded fluorescent voltage indicator, simultaneously optimizing its brightness and membrane localization using our microscopy-guided cell-picking strategy. We produced the high-performance opsin-based fluorescent voltage reporter Archon1 and demonstrated its utility by imaging spiking and millivolt-scale subthreshold and synaptic activity in acute mouse brain slices and in larval zebrafish in vivo. We also measured postsynaptic responses downstream of optogenetically controlled neurons in C. elegans.

Indexed as

RoboticsAnimalsBrainCaenorhabditis elegansCell SeparationDirected Molecular EvolutionFemaleFlow CytometryFluorescenceGene LibraryGenes, ReporterHEK293 CellsHippocampusHumansLuminescent ProteinsMaleLuminescent Proteins

Identifiers

PMID29483642
PMCPMC5866759
OpenAlexW2792403811

What OpenQuestion holds

Textmetadata
LicenceTDM
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.