Institute of Molecular Systems Biology · ETH Zürich

Systems Biology of
Transcriptional Regulatory Networks

We study how transcriptional regulation enable cells to adapt to environmental changes, from the principles dictating molecular interactions to the organization and regulatory mechanisms of their complex networks.

Our Research Tools & Data GitHub Institute website

Research Focus

How do transcriptional regulatory networks enable cells to adapt to their environment ?

We work at the scales of molecular interactions and networks, focusing on transcription factors: the DNA-binding proteins regulating gene expression. To that aim, we use and develop high-throughput sequencing-based methods to systematically characterize transcriptional regulatory networks.

Our model systems are microbes, with a particular focus on bacterial pathogens and how their regulatory networks drive the establishment of infections in humans.

Topic 01
The emergence of infection in bacterial pathogens

We study bacterial pathogens to understand how transcriptional regulatory networks evolve to integrate new genetic material, and how they enable the phenotypic adaptation needed for infections. To address this question, we leverage unique high-throughput methods to characterize regulatory networks at scale. Using these networks, we can interpret data from infections to identify and characterize molecular interactions that allow bacterial pathogens to adapt to the human body and cause infections.
Additionally, we study regulatory network evolution within and between pathogenic species to identify core regulatory interactions conserved across pathogenic isolates and reveal how changes in gene content reshape regulatory networks.

Topic 02
The molecular rules of regulatory network organization

We aim to define transferable molecular rules that dictate transcription factor regulatory interactions to enable the prediction and manipulation of the networks driving gene expression responses.To that aim, we combine high-throughput assays with computational modeling to decode and predict transcription factors DNA-binding specificity. Using these tools, we aim to investigate how DNA-binding preferences evolve to bridge the gap between TF protein sequence and function.
Additionally, we aim to explore the use of such predictive tools for the design of new-to-nature transcription factors with on-demand functions.

Gene regulatory network diagram, frame 1 Gene regulatory network diagram, frame 2 Gene regulatory network diagram, frame 3 Gene regulatory network diagram, frame 4 Gene regulatory network diagram, frame 5

Methods

We use and develop high-throughput sequencing-based approaches to characterize transcriptional regulatory networks. Particularly, we have developed a high-throughput automated pipeline for genome-wide characterization of transcription factor interactions at the scale of entire regulatory networks. With such tools, we can probe the molecular interactions of all transcription factors of a given organism, opening the door to study new questions at the network scale.

We study different aspects of transcription factor biology: the interactions of transcription factors with DNA, and the molecular signals sensed by transcription factors to modulate their regulatory activity. With different methods addressing these two aspects, we study the multi-layer interplay between the transcriptional regulatory networks and the metabolic and protein-protein interaction networks, to provide a systematic understanding of how different molecular stimuli shape phenotypes through these networks.


Tools & Data

Open softwares and resources

PoolPy logo
Web app Group testing

A web platform to design and decode combinatorial group testing strategies to reduce the amount of measurements needed across assay types, following user-defined constraints such as time, cost or sample dilution.

PoolPy

Publications

Selected work

YearPublication
2026 Hurto RL, Schroeder JW, Trouillon J, et al. Profiling large-scale protein occupancy on bacterial genomes using IPOD-HR. Nature Protocols. DOI →
2025 Trouillon J, Huber AE, Trabesinger Y, Sauer U. Predicting input signals of transcription factors in Escherichia coli. Molecular Systems Biology. DOI →
2025 Talamanca L, Trouillon J. PoolPy: Flexible Group Testing Design for Large-Scale Screening. Preprint, arXiv:2509.03481. DOI →
2024 Holbrook-Smith D, Trouillon J, Sauer U. Metabolomics and Microbial Metabolism: Toward a Systematic Understanding. Annual Review of Biophysics, 53:41–64. DOI →
2023 Trouillon J, Doubleday PF, Sauer U. Genomic footprinting uncovers global transcription factor responses to amino acids in Escherichia coli. Cell Systems, 14(10), 860–871. DOI →

Full list on Google Scholar →


People

The team

Julian Trouillon
Dr. Julian Trouillon
Group Leader
Kian Bigovic Villi
Kian Bigovic Villi
PhD Student
Alexandre Dentler
Alexandre Dentler
PhD Student
Luc Lafrenaye
Luc Lafrenaye
PhD Student
Stefanie Loosli
Stefanie Loosli
PhD Student

Join Us

Work with us

PhDs & postdocs

We are always happy to hear from motivated students and postdocs interested in transcriptional regulation, molecular biology or computational biology. Get in touch with your CV and a short note on your interests.

Get in touch

Master's projects

We continuously offer projects for Master students, with flexible durations. Projects can be experimental, computational, or a mix of both, focused on our main research topics. Reach out to learn more about open projects or the possibility to design one where our interests meet.

Project list

Contact

Find us

Institute of Molecular Systems Biology
ETH Zürich
Otto-Stern-Weg 3, HPM
8093 Zürich, Switzerland

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Map showing the lab's location at ETH Zürich Hönggerberg
© 2026 Trouillon Lab — Institute of Molecular Systems Biology, ETH Zürich