We study transcriptional and translational regulation in microorganisms. Our dual aim is to understand regulatory logic and to control it through artificial gene expression engineering.
Activities
AI-driven promoter & σ-factor mapping:
We generate large-scale high-dimensional experimental datasets and integrate them with advanced ML models to decode σ-factor recognition of promoter sequences and to predict regulatory function across organisms (promoter prediction).
Relevant publications (click to expand)
Published
- Khan EA, Rückert-Reed C, Dahiya GS, Tietze L, Fages-Lartaud M, Busche T, Kalinowski J, Shingler V, Lale R. (2025) High-resolution mapping of Sigma Factor DNA Binding Sequences using Artificial Promoters, RNA aptamers and Deep Sequencing. Nucleic Acids Research.
- Dahiya GS, Bakken TI, Fages-Lartaud M, Lale R. (2023) From Context to Code: Rational De Novo DNA Design and Predicting Cross-Species DNA Functionality Using Deep Learning Transformer Models. Preprint @ bioRxiv.
Unpublished
- Teigset E, Khan EA, Rückert-Reed C, Busche T, Sebek Z, Sudzinova P, Sanderova H, Krasny L, Dahiya GS, Lale R. From sequence to function: Prediction of promoter functionality across diverse sigma factors using a transformer model trained on millions of artificial promoters.
- Khan EA, Dahiya GS, Rückert-Reed C, Busche T, Kalinowski J, Shingler V, Lale R. Genome-Scale Transcriptome Sequencing and 5′-End Mapping Reveal RpoN-Regulated Transcription Units and Promoters in Pseudomonas putida.
GeneEE platform:
To go beyond working on single model organisms, we systematically generate and characterise artificial promoter/5′-UTR sequences to expand functional annotation and uncover context-dependent rules. The data generated also serve as training datasets in AI-driven promoter prediction.
Relevant publications (click to expand)
Published
- Wong CFA, Zhang S, Tietze L, Dahiya GS, Lale R. (2025) Engineering Artificial 5′ Regulatory Sequences for Thermostable Protein Expression in the Extremophile Thermus thermophilus. Synthetic Biology
- Blanch-Asensio M, Tadimarri VS, Martinez RP, Dahiya GS, Lale R, Sankaran S. (2025) Encapsulation-enhanced genetic switches in lactobacilli. Journal of Controlled Release.
- Tietze L, Mangold A, Hoff M, Lale R.(2022) Identification and cross-characterisation of artificial promoters and 5' untranslated regions in Vibrio natriegens. Frontiers in Bioengineering and Biotechnology - Synthetic Biology.
- Lale R, Tietze L, Fages-Lartaud M, Nesje J, Onsager I, Engelhardt K, Wong CFA, Akan M, Hummel N, Kalinowski J, Rückert C, Hohmann-Marriott MF. (2022) A universal approach to gene expression engineering. OUP Synthetic Biology
- Fages-Lartaud M, Prone W, Mueller Y, Lale R. (2022) Method for engineering artificial bidirectional promoters. Preprint @ Research Square.
- Tietze L, Lale R. (2021) Importance of the 5′ Regulatory Region to Bacterial Synthetic Biology Applications. Microbial Biotechnology
Unpublished
- Wong CFA, Fages-Lartaud M, Lale R. Engineering of a microbiome-derived Xylo-Oligosaccharide (XOS) utilization pathway in Escherichia coli via artificial promoters.
- Fages-Lartaud M, Rückert-Reed C, Busche T, Kalinowski J, Lale R, Hohmann-Marriott MF. A universal method for activating and balancing gene expression in metabolic pathways.
Microfluidics for single-cell and single-template analysis:
We use droplet- and chip-based platforms to quantify transcription and translation dynamics at high resolution.
Relevant publications (click to expand)
Published
- Bhujbal SV, Dekov M, Ottesen V, Dunker K, Lale R, Sletmoen M. (2020) Effect of design geometry, exposure energy, cytophilic molecules, cell type and load in fabrication of single-cell arrays using micro-contact printing. Scientific Reports.
- Arnfinnsdottir NB, Ottesen V, Lale R, Sletmoen M. (2015) The design of simple bacterial microarrays. Development towards immobilizing single living bacteria on predefined micro-sized spots on patterned surfaces. PLOS ONE.
Unpublished
- Totlani K, Khan EA, Ahmed H, Lale R, Stokke BT*. Integrated microdroplet workflow for high-throughput cell-free transcription in double emulsion picoreactors.
Metagenomic screening & lysis-on-demand:
We combine microfluidics for high-throughput functional screening of complex communities, supported by microfluidic lysis-on-demand to access otherwise hidden genetic diversity.
Relevant publications (click to expand)
Published
- Wong CFA, Bhujbal SV, van Vliet L, Guo C, Sletmoen M, Stokke BT, Hollfelder F, Lale R. (2021) A Titratable Cell Lysis-on-Demand System for Droplet-Compartmentalised Ultrahigh-Throughput Screening in Functional Metagenomics and Directed Evolution. ACS Synthetic Biology.
- Lewin A, Lale R, Wentzel A. (2017) Expression Platforms for Functional Metagenomics – Emerging technology options beyond Escherichia coli. In: Functional Metagenomics: Tools and Applications. Springer.
- Aakvik T, Lale R, Liles M, Valla S. (2011)Metagenomic libraries for functional screening, Ch 22. In: Handbook of Molecular Microbial Ecology I. Wiley.
Unpublished
- Wong CFA, Fages-Lartaud M, Lale R. Engineering of a microbiome-derived Xylo-Oligosaccharide (XOS) utilization pathway in Escherichia coli via artificial promoters.
Organisms we work with
Our work is not limited to a single model organism. We routinely work across a wide range of bacteria and yeast to test and validate regulatory principles.
Gram-negative bacteria
Cupriavidus necator, Escherichia coli, Pseudomonas putida, Synechococcus sp., Thermus thermophilus, Vibrio natriegens
Gram-positive bacteria
Bacillus subtilis, Corynebacterium glutamicum, Lactiplantibacillus plantarum, Streptomyces albus, Streptomyces lividans
Synthetic cell
JCVI syn1 & syn3
Yeast
Saccharomyces cerevisiae