ArticleNucleic acids research2021
A simplified strategy for titrating gene expression reveals new relationships between genotype, environment, and bacterial growth.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- Programmable CRISPRtune dissects the transcriptional repressive activity of MeCP2.bioRxiv : the preprint server for biology · 2026Article
- Mycobacterial cell division arrest and smooth-to-rough envelope transition using CRISPRi-mediated genetic repression systems.FEBS open bio · 2026Article
- Oligonucleotide genetics forbioRxiv : the preprint server for biology · 2026Article
- Systematic CRISPRi screening reveals genetic modulators ofbioRxiv : the preprint server for biology · 2026Article
- Orthogonal chemical genomics approaches reveal genomic targets for increasing anaerobic chemical tolerance inmSystems · 2026Article
- Essentialome-Wide Multigenerational Imaging Reveals Mechanistic Origins of Cell Growth Laws.bioRxiv : the preprint server for biology · 2025Article
- Considering Metabolic Context in Enzyme Evolution and Design.Biochemistry · 2025Review
- Dissecting the effects of single amino acid substitutions in SARS-CoV-2 Mpro.Protein science : a publication of the Protein Society · 2025Article
- High-density CRISPRi screens reveal diverse routes to improved acclimation in cyanobacteria.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Rationally designed pooled CRISPRi-seq uncovers an inhibitor of bacterial peptidyl-tRNA hydrolase.Cell reports · 2024Article
- Guide RNA structure design enables combinatorial CRISPRa programs for biosynthetic profiling.Nature communications · 2024Article
- Integrating bacterial molecular genetics with chemical biology for renewed antibacterial drug discovery.The Biochemical journal · 2024Review
- CRISPRi functional genomics in bacteria and its application to medical and industrial research.Microbiology and molecular biology reviews : MMBR · 2024Review
- ORBIT for E. coli: kilobase-scale oligonucleotide recombineering at high throughput and high efficiency.Nucleic acids research · 2024Article
- A dose-response model for statistical analysis of chemical genetic interactions in CRISPRi screens.PLoS computational biology · 2024Article
- A continuous epistasis model for predicting growth rate given combinatorial variation in gene expression and environment.Cell systems · 2024Article
- Article
- Gradients in gene essentiality reshape antibacterial research.FEMS microbiology reviews · 2022Review
- Unraveling the mechanisms of intrinsic drug resistance inFrontiers in cellular and infection microbiology · 2022Review
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A lack of high-throughput techniques for making titrated, gene-specific changes in expression limits our understanding of the relationship between gene expression and cell phenotype. Here, we present a generalizable approach for quantifying growth rate as a function of titrated changes in gene expression level. The approach works by performing CRISPRi with a series of mutated single guide RNAs (sgRNAs) that modulate gene expression. To evaluate sgRNA mutation strategies, we constructed a library of 5927 sgRNAs targeting 88 genes in Escherichia coli MG1655 and measured the effects on growth rate. We found that a compounding mutational strategy, through which mutations are incrementally added to the sgRNA, presented a straightforward way to generate a monotonic and gradated relationship between mutation number and growth rate effect. We also implemented molecular barcoding to detect and correct for mutations that 'escape' the CRISPRi targeting machinery; this strategy unmasked deleterious growth rate effects obscured by the standard approach of ignoring escapers. Finally, we performed controlled environmental variations and observed that many gene-by-environment interactions go completely undetected at the limit of maximum knockdown, but instead manifest at intermediate expression perturbation strengths. Overall, our work provides an experimental platform for quantifying the phenotypic response to gene expression variation.
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Registered trials
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