Evidence map›Paper›PMID 28985507›Full record

ArticleMolecular cell2017

Randomized CRISPR-Cas Transcriptional Perturbation Screening Reveals Protective Genes against Alpha-Synuclein Toxicity.

Ying-Chou Chen, Fahim Farzadfard, Nava Gharaei, William C W Chen, Jicong Cao, Timothy K Lu

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

20 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
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  10. Article
  11. Proteome-Scale Mapping of Perturbed Proteostasis in Living Cells.Cold Spring Harbor perspectives in biology · 2020
    Review
  12. Article
  13. Utilization of the CRISPR-Cas9 Gene Editing System to Dissect Neuroinflammatory and Neuropharmacological Mechanisms in Parkinson's Disease.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019
    Review
  14. Review
  15. Article
  16. Review
  17. Unbiased Screens for Modifiers of Alpha-Synuclein Toxicity.Current neurology and neuroscience reports · 2019
    Review
  18. Review
  19. Delivery systems of CRISPR/Cas9-based cancer gene therapy.Journal of biological engineering · 2018
    Review
  20. 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

6 authors at 2 institutions in 1 country.

Ying-Chou ChenSynthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Fahim FarzadfardSynthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; MIT Microbiology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering and Electrical Engineering & Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Nava GharaeiMCO Graduate Program, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
William C W ChenSynthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Jicong CaoSynthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Timothy K LuSynthetic Biology Group, MIT Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; MIT Microbiology Program, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering and Electrical Engineering & Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: timlu@mit.edu.
Synthetic Biologics (United States) · USHarvard University · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
MIT Center for Integrative Synthetic BiologyP50GM098792 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WEISS, RON · 2013 to 2017
$11.0M
NIDDK NIH HHS P30 DK043351NIGMS NIH HHS P50 GM098792
6 · The paper itself

Abstract

The genome-wide perturbation of transcriptional networks with CRISPR-Cas technology has primarily involved systematic and targeted gene modulation. Here, we developed PRISM (Perturbing Regulatory Interactions by Synthetic Modulators), a screening platform that uses randomized CRISPR-Cas transcription factors (crisprTFs) to globally perturb transcriptional networks. By applying PRISM to a yeast model of Parkinson's disease (PD), we identified guide RNAs (gRNAs) that modulate transcriptional networks and protect cells from alpha-synuclein (αSyn) toxicity. One gRNA identified in this screen outperformed the most protective suppressors of αSyn toxicity reported previously, highlighting PRISM's ability to identify modulators of important phenotypes. Gene expression profiling revealed genes differentially modulated by this strong protective gRNA that rescued yeast from αSyn toxicity when overexpressed. Human homologs of top-ranked hits protected against αSyn-induced cell death in a human neuronal PD model. Thus, high-throughput and unbiased perturbation of transcriptional networks via randomized crisprTFs can reveal complex biological phenotypes and effective disease modulators.

Indexed as

CRISPR-Cas SystemsGene Regulatory NetworksTranscription, Geneticalpha-SynucleinCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsGene Expression ProfilingGene Expression RegulationHigh-Throughput Screening AssaysHumansModels, BiologicalNeuronsParkinson DiseasePhenotypeRNA, Guide, CRISPR-Cas SystemsSaccharomyces cerevisiaealpha-SynucleinRNA, Guide, CRISPR-Cas SystemsTranscription Factorsalpha-synucleinCRISPR screeningglobal transcriptional perturbationsParkinson’s diseasePerturbing Regulatory Interactions by Synthetic ModulatorsPRISMrandomized gRNA librarysynthetic transcription factors

Identifiers

PMID28985507
PMCPMC5702536
OpenAlexW2763182809

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.