Nature Search

Transcription factor binding kinetics constrain noise suppression via negative feedback

Live cell imaging have recently revealed that transcription factors spend up to 4 min to find and bind their chromosomal binding site. Grönlund et al. show that this slow search process leads to tradeoffs between strength and speed of negative autoregulation for effective noise suppression.

Andreas Grönlund
Per Lötstedt
Johan Elf
Research14 May 2013
Nature Communications

Volume: 4, P: 1-5
Phenotypic drug susceptibility testing for Mycobacterium tuberculosis variant bovis BCG in 12 hours

Long turnaround times for phenotypic drug susceptibility testing (pDST) impact the efficacy of tuberculosis treatment. Here, the authors present a rapid pDST approach for slow-growing mycobacteria that can be conducted in less than 12 h.

Buu Minh Tran
Jimmy Larsson
Johan Elf
ResearchOpen Access10 May 2025
Nature Communications

Volume: 16, P: 1-12
Culture-free detection of bacteria from blood for rapid sepsis diagnosis

M. Henar Marino Miguélez
Mohammad Osaid
Wouter van der Wijngaart
ResearchOpen Access25 Aug 2025
npj Digital Medicine

Volume: 8, P: 1-11
Anti-correlation of LacI association and dissociation rates observed in living cells

What makes a transcription factor (TF) binding site “strong”: slow TF dissociation, or fast TF association? Kandavalli et al found that stronger sites had both slower dissociation and faster association compared to weaker sites in vivo.

Vinodh Kandavalli
Spartak Zikrin
Daniel Jones
ResearchOpen Access17 Jan 2025
Nature Communications

Volume: 16, P: 1-9
Direct measurement of transcription factor dissociation excludes a simple operator occupancy model for gene regulation

Johan Elf and colleagues developed a single-molecule chase assay to measure the time a single transcription factor is bound at a specific chromosomal operator site, which they use to examine the dynamics of binding of the Lac repressor dimer at the native lac operator in Escherichia coli. Their findings do not support the simple operator occupancy model and suggest a role for non-equilibrium transcription factor kinetics in E. coli gene regulation.

Petter Hammar
Mats Walldén
Johan Elf
Research23 Feb 2014
Nature Genetics

Volume: 46, P: 405-408
Extracting intracellular diffusive states and transition rates from single-molecule tracking data

This paper reports an analytical method for single-particle tracking data. It identifies diffusive states of intracellular proteins and the rates of transition between them.

Fredrik Persson
Martin Lindén
Johan Elf
Research10 Feb 2013
Nature Methods

Volume: 10, P: 265-269
The Escherichia coli chromosome moves to the replisome

It is debated whether the two replisomes in Escherichia coli move independently along the two chromosome arms during replication or if they remain spatially confined. Here the authors present data in support of spatially confined replisomes.

Konrad Gras
David Fange
Johan Elf
ResearchOpen Access17 Jul 2024
Nature Communications

Volume: 15, P: 1-13
Author Correction: RecA finds homologous DNA by reduced dimensionality search

Jakub Wiktor
Arvid H. Gynnå
Johan Elf
Amendments and CorrectionsOpen Access12 Nov 2021
Nature

Volume: 600, P: E11
Rapid antibiotic susceptibility testing and species identification for mixed samples

Rapid antibiotic susceptibility testing (AST) is needed. Here the authors report a method for phenotypic AST at the single cell level, using a microfluidic chip that allows for subsequent genotyping with in situ FISH; they apply this to a mixed sample of 7 species and 4 antibiotics.

Vinodh Kandavalli
Praneeth Karempudi
Johan Elf
ResearchOpen Access20 Oct 2022
Nature Communications

Volume: 13, P: 1-8
A non-lethal method for detection of Bonamia ostreae in flat oyster (Ostrea edulis) using environmental DNA

Louise von Gersdorff Jørgensen
Johan Wedel Nielsen
Kurt Buchmann
ResearchOpen Access30 Sept 2020
Scientific Reports

Volume: 10, P: 1-9
RecA finds homologous DNA by reduced dimensionality search

Observations of rapid repair of double-stranded DNA breaks in sister choromosomes in Escherichia coli are consistent with a reduced-dimensionality-search model of RecA-mediated repair.

Jakub Wiktor
Arvid H. Gynnå
Johan Elf
ResearchOpen Access01 Sept 2021
Nature

Volume: 597, P: 426-429
DNA surface exploration and operator bypassing during target search

Single-molecule fluorescence resonance energy transfer and real-time confocal laser tracking with fluorescence correlation spectroscopy together characterize how individual lac repressor molecules bypass operator sites while exploring the DNA surface at microsecond timescales.

Emil Marklund
Brad van Oosten
Sebastian Deindl
Research24 Jun 2020
Nature

Volume: 583, P: 858-861
Real-time single-molecule 3D tracking in E. coli based on cross-entropy minimization

Single-molecule 3D tracking is critical to understand macromolecular dynamics but achieving this at a sub-millisecond resolution remains challenging. Here the authors present a 3D tracking method based on cross-entropy minimization and the true excitation point spread function.

Elias Amselem
Bo Broadwater
Johan Elf
ResearchOpen Access11 Mar 2023
Nature Communications

Volume: 14, P: 1-11
Delay-induced anomalous fluctuations in intracellular regulation

Direct negative feedback decreases fluctuations in homoeostatic control, but intracellular regulatory systems are indirect. Here, an analytical expression is derived to show that indirect feedback in transcription and translation leads to more fluctuations for intermediate delays but not for long delays.

Andreas Grönlund
Per Lötstedt
Johan Elf
Research09 Aug 2011
Nature Communications

Volume: 2, P: 1-7
Pointwise error estimates in localization microscopy

Super-resolution localization microscopy produces biophysical information in the form of estimated positions of single molecules. Here, Lindénet al. estimate the uncertainty of single localizations, and show that this additional information can improve data analysis and localization precision.

Martin Lindén
Vladimir Ćurić
Johan Elf
ResearchOpen Access03 May 2017
Nature Communications

Volume: 8, P: 1-9
Author Correction: tRNA tracking for direct measurements of protein synthesis kinetics in live cells

Ivan L. Volkov
Martin Lindén
Magnus Johansson
Amendments and Corrections05 Apr 2019
Nature Chemical Biology

Volume: 15, P: 757
Time-resolved imaging-based CRISPRi screening

DuMPLING (dynamic μ-fluidic microscopy phenotyping of a library before in situ genotyping) enables screening of dynamic phenotypes in strain libraries and was used here to study genes that coordinate replication and cell division in Escherichia coli.

Daniel Camsund
Michael J. Lawson
Johan Elf
Research18 Nov 2019
Nature Methods

Volume: 17, P: 86-92
Pooled optical screening in bacteria using chromosomally expressed barcodes

Optical pooled screening of libraries with genomic barcodes has not previously been achieved in bacteria. Here we describe such a method in E. coli and apply it to measure the intracellular maturation time of 84 red fluorescent proteins.

Ruben R. G. Soares
Daniela A. García-Soriano
Johan Elf
ResearchOpen Access03 Jun 2025
Communications Biology

Volume: 8, P: 1-9
Direct measurements of mRNA translation kinetics in living cells

Metelev et al. use single-molecule tracking to study kinetics of translation directly in E. coli cells, and how it is affected by translation inhibitors and rRNA mutations. Their results support widespread 70S re-initiation on mRNAs.

Mikhail Metelev
Erik Lundin
Magnus Johansson
ResearchOpen Access06 Apr 2022
Nature Communications

Volume: 13, P: 1-13
Effects of macromolecular crowding and DNA looping on gene regulation kinetics

Proteins seek out binding sites on DNA through diffusion and also by sliding along the strand. Although ‘roadblocks’—other bound proteins on the DNA strand—slow things down, it seems that looping of the DNA aids the search process.

Gene-Wei Li
Otto G. Berg
Johan Elf
Research15 Mar 2009
Nature Physics

Volume: 5, P: 294-297
tRNA tracking for direct measurements of protein synthesis kinetics in live cells

Combination of single-molecule tracking experiments and machine-learning approaches to monitor diffusional state transitions between ribosome-bound and free tRNAs allows codon resolution measurements of translation kinetics.

Ivan L. Volkov
Martin Lindén
Magnus Johansson
Research16 May 2018
Nature Chemical Biology

Volume: 14, P: 618-626
Lost in presumption: stochastic reactions in spatial models

Physical modeling is increasingly important for generating insights into intracellular processes. We describe situations in which combined spatial and stochastic aspects of chemical reactions are needed to capture the relevant dynamics of biochemical systems.

Anel Mahmutovic
David Fange
Johan Elf
Comments & Opinion07 Dec 2012
Nature Methods

Volume: 9, P: 1163-1166
Summing up the noise in gene networks

Johan Paulsson
Research29 Jan 2004
Nature

Volume: 427, P: 415-418
Three-dimensional localization and tracking of chromosomal loci throughout the Escherichia coli cell cycle

The intracellular position of genes in the chromosome may impact their expression. To measure the 3D positions of chromosomal loci over the bacterial cell cycle, we have developed a combination of microfluidics, optics, and deep learning.

Praneeth Karempudi
Konrad Gras
Johan Elf
ResearchOpen Access05 Nov 2024
Communications Biology

Volume: 7, P: 1-11
Imaging-based screens of pool-synthesized cell libraries

This Perspective describes technological advances for imaging-based screening of diverse cellular phenotypes.

Michael Lawson
Johan Elf
Reviews15 Feb 2021
Nature Methods

Volume: 18, P: 358-365
Emissions and exposures of graphene nanomaterials, titanium dioxide nanofibers, and nanoparticles during down-stream industrial handling

Karin Lovén
Sara M. Franzén
Maria Hedmer
ResearchOpen Access16 Jun 2020
Journal of Exposure Science & Environmental Epidemiology

Volume: 31, P: 736-752
Single-cell microscopy of suspension cultures using a microfluidics-assisted cell screening platform

This protocol describes a microfluidics platform, termed 'MACS', for single-cell microscopy of suspension cells. MACS temporarily immobilizes the cells, allowing for high-throughput and high-resolution imaging, cell sorting, and single-molecule detection.

Burak Okumus
Charles J Baker
Johan Paulsson
Protocols21 Dec 2017
Nature Protocols

Volume: 13, P: 170-194
The highly dynamic nature of bacterial heteroresistance impairs its clinical detection

Bacterial populations can show heteroresistance, where an antibiotic resistant subpopulation is part of a susceptible one. Pereira et al. show in Escherichia coli and Salmonella enterica that disk diffusion, a common antibiotic susceptibility test, underestimates the occurrence of heteroresistance in clinical isolates.

Cátia Pereira
Jimmy Larsson
Dan I. Andersson
ResearchOpen Access05 May 2021
Communications Biology

Volume: 4, P: 1-12
Single molecule tracking fluorescence microscopy in mitochondria reveals highly dynamic but confined movement of Tom40

Anton Kuzmenko
Stoyan Tankov
Vasili Hauryliuk
ResearchOpen Access14 Dec 2011
Scientific Reports

Volume: 1, P: 1-7

Search

Transcription factor binding kinetics constrain noise suppression via negative feedback

Phenotypic drug susceptibility testing for Mycobacterium tuberculosis variant bovis BCG in 12 hours

Culture-free detection of bacteria from blood for rapid sepsis diagnosis

Anti-correlation of LacI association and dissociation rates observed in living cells

Direct measurement of transcription factor dissociation excludes a simple operator occupancy model for gene regulation

Extracting intracellular diffusive states and transition rates from single-molecule tracking data

The Escherichia coli chromosome moves to the replisome

Author Correction: RecA finds homologous DNA by reduced dimensionality search

Rapid antibiotic susceptibility testing and species identification for mixed samples

A non-lethal method for detection of Bonamia ostreae in flat oyster (Ostrea edulis) using environmental DNA

RecA finds homologous DNA by reduced dimensionality search

DNA surface exploration and operator bypassing during target search

Real-time single-molecule 3D tracking in E. coli based on cross-entropy minimization

Delay-induced anomalous fluctuations in intracellular regulation

Pointwise error estimates in localization microscopy

Author Correction: tRNA tracking for direct measurements of protein synthesis kinetics in live cells

Time-resolved imaging-based CRISPRi screening

Pooled optical screening in bacteria using chromosomally expressed barcodes

Direct measurements of mRNA translation kinetics in living cells

Effects of macromolecular crowding and DNA looping on gene regulation kinetics

tRNA tracking for direct measurements of protein synthesis kinetics in live cells

Lost in presumption: stochastic reactions in spatial models

Summing up the noise in gene networks

Three-dimensional localization and tracking of chromosomal loci throughout the Escherichia coli cell cycle

Imaging-based screens of pool-synthesized cell libraries

Emissions and exposures of graphene nanomaterials, titanium dioxide nanofibers, and nanoparticles during down-stream industrial handling

Single-cell microscopy of suspension cultures using a microfluidics-assisted cell screening platform

The highly dynamic nature of bacterial heteroresistance impairs its clinical detection

Single molecule tracking fluorescence microscopy in mitochondria reveals highly dynamic but confined movement of Tom40

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