A5056921594- Diffusion and Search Dynamics
- Bacteriophages and microbial interactions
- Single-cell and spatial transcriptomics
- Image and Signal Denoising Methods
- Sparse and Compressive Sensing Techniques
- CRISPR and Genetic Engineering
- Advanced Fluorescence Microscopy Techniques
- Gene Regulatory Network Analysis
- RNA and protein synthesis mechanisms
- Image Processing Techniques and Applications
- Bacterial Genetics and Biotechnology
- Advanced Optimization Algorithms Research
- Cell Image Analysis Techniques
- Microbial Community Ecology and Physiology
- Matrix Theory and Algorithms
- Photoreceptor and optogenetics research
- Bioactive Compounds and Antitumor Agents
- Polyamine Metabolism and Applications
- Antibiotic Resistance in Bacteria
- Genetics, Bioinformatics, and Biomedical Research
- Iterative Methods for Nonlinear Equations
- DNA and Nucleic Acid Chemistry
- Genomics and Phylogenetic Studies
- Monoclonal and Polyclonal Antibodies Research
- Gut microbiota and health
Science for Life Laboratory
2019-2025
Uppsala University
2019-2025
Linköping University
2012-2016
Sequence-specific binding of proteins to DNA is essential for accessing genetic information. We derive a model that predicts an anticorrelation between the macroscopic association and dissociation rates proteins. tested thousands different lac operator sequences with protein microarray by observing kinetics individual repressor molecules in single-molecule experiments. found sequence specificity mainly governed efficiency which recognizes targets. The variation probability recognizing...
The rate at which transcription factors (TFs) bind their cognate sites has long been assumed to be limited by diffusion, and thus independent of binding site sequence. Here, we systematically test this assumption using cell-to-cell variability in gene expression as a window into the vivo association dissociation kinetics model factor LacI. Using stochastic relationship between kinetics, performed single-cell measurements infer rates for set 35 different LacI sites. We found that both...
The blood of a septic patient contains only few bacteria per milliliter. Recently, various techniques have been developed for extracting these from sample. Independent how are separated the cells, we want to learn them treat infection. Here, describe phenotypic Antibiotic Susceptibility Test can be executed with single bacterial cell by making averages over time instead populations, if account experimental noise and cell-to-cell variability. We use method make preliminary estimates long it...
Transcription factors (TFs) efficiently locate their target DNA sequences by combining three-dimensional diffusion and one-dimensional sliding on nonspecific DNA. In order to slide fast but still bind strongly at specific sequences, TFs have been proposed change from search conformation recognition upon binding. For the lac repressor of E. coli, LacI, folding hinge helices has implicated in conformational switch. Here, we tested how flexibility region impacts speed stability Based molecular...
Mechanistic details of the signal recognition particle (SRP)-mediated insertion membrane proteins have been described from decades in vitro biochemical studies. However, dynamics pathway inside living cell remain obscure. By combining vivo single-molecule tracking with numerical modeling and simulated microscopy, we constructed a quantitative reaction-diffusion model SRP cycle. Our results suggest that SRP-ribosome complex finds its target, membrane-bound translocon, through combination...
Abstract The intracellular position of genes may impact their expression, but it has not been possible to accurately measure the 3D chromosomal loci. In 2D, loci can be tracked using arrays DNA-binding sites for transcription factors (TFs) fused with fluorescent proteins. However, same 2D data result from different trajectories. Here, we have developed a deep learning method super-resolved astigmatism-based localization in live E. coli cells which enables precision better than 61 nm at...
Abstract 3D localization of fluorescent proteins (FPs) in living bacteria has been challenging due to the low signal-to-background ratio FPs and relatively uncertain positioning cells optical reference system. Using mother-machine microfluidic devices together with deep learning, we present an approach that enables accurate Escherichia coli over long periods. We describe a method simulate ground truth training data for learning network based on background models generated from experimental...
Abstract Optical pooled screening is an important tool to study dynamic phenotypes for libraries of genetically engineered cells. However, the desired engineering often requires that barcodes used in situ genotyping are expressed from chromosome. This has not been possible bacteria. Here we describe a method with genomic Escherichia. coli . The applied measure intracellular maturation time 81 red fluorescent proteins.
The multilinear least-squares (MLLS) problem is an extension of the linear problem. difference that a operator used in place matrix-vector product. MLLS typically large-scale characterized by large number local minimizers. It originates, for instance, from design filter networks. We present global search strategy allows moving one minimizer to better one. efficiency this illustrated results numerical experiments performed some problems related
The rate at which transcription factors (TFs) bind their cognate sites has long been assumed to be limited by diffusion, and thus independent of binding site sequence. Here, we systematically test this assumption using cell-to-cell variability in gene expression as a window into the vivo association dissociation kinetics model factor LacI. Using stochastic relationship between kinetics, performed single-cell measurements infer rates for set 35 different LacI sites. We found that both...
Abstract Our ability to connect genotypic variation biologically important phenotypes has been seriously limited by the gap between live cell microscopy and library-scale genomic engineering. Specifically, this restricted studies of intracellular dynamics one strain at a time thus, generally, impact genes with known function. Here we show how in situ genotyping library E. coli strains after time-lapse imaging microfluidic device overcomes problem. We determine 235 different CRISPR...