DREAMY - Distributed Algorithms for Microbiological Systems

Objective

A key advantage of biological computing devices is their ability to sense, compute, and especially to respond to their biological environment, e.g., bacteria can be programmed to act as autonomous robots within the human body. Local presence of certain molecules in the environment allows sensing of neighboring cell types and acting accordingly, e.g., by activating an immune response. Current designs of synthetic circuits in bacteria, however, face severe resource limitations: each genetic part added to the cell imposes an additional burden, becoming progressively toxic for the cell.

The most common design techniques for biological logic gates rely on gene regulation via DNA-binding proteins, nucleic acid (DNA/RNA) interactions, or more recently the CRISPR machinery. Each comes with its own constraints: like limited availability of orthogonal signals for use within the cell (DNA-binding), small dynamic range (RNA-based), or reduced growth rates (the CRISPR machinery). This has led to recent efforts to distribute circuits among several cells to reduce the resource load per cell, taking the formative steps towards distributed bacterial circuits.

The DREAMY research project seeks to develop innovative solutions to the problem of building distributed circuits in bacteria from an algorithmic, theoretical perspective that contributes to real-world implementable solutions.

News

Activities

We organize the following related workshops and seminar series:

• CELLS - Workshop on Computing among Cells: co-located with the International Symposium on DIStributed Computing (DISC)
• HicDiesMeus - Working Group on Highly Constrained Discrete Agents for Modeling Natural Systems: seminar series on problems from physical, biological, and sociological domains within a distributed computing context

Project members

Matthias Függer

Principal Investigator
chip design, distributed algorithms

Thomas Nowak

Principal Investigator
distributed algorithms, stochastic processes

Manish Kushwaha

Local Coordinator @ Micalis
genetic circuits, phage communication

Dylan Baumann

PhD Student @ TU Wien

Joffroy Beauquier

Project Member
population protocols

Benedikt Bollig

Project Member
AI, model discovery

Catherine Bonnet

Project Member
control theory

Janna Burman

Project Member
population protocols

Arnaud Casteigts

Project Member
dynamic networks

Alissia Chantout

Intern @ Université Paris Cité

Thomas Chatain

Project Member
timed concurrency, process mining

Parth Chavan

Intern @ École polytechnique

Mariapia D'Urso

PhD Student @ ENS Paris-Saclay

Jean-Loup Faulon

Project Member
bio-retrosynthesis, biosensors

Laurent Fribourg

Project Member
hybrid systems

Dhrubajyoti Ghosh

PhD Student @ ENS Paris-Saclay

Stefan Haar

Project Member
concurrency, partial orders, systems biology, ecology

Alexandra Loudieres

PhD Student @ ENS Paris-Saclay

Sevinj Mahmudova

Intern @ MIT

Mélanie Pietri

PhD Student
bioproduction, predictive models, optimization

Cristina Stoica

Project Member
control theory, cooperative control of multi-agent systems

Kerian Thuillier

Postdoc @ ENS Paris-Saclay

Paul Zeinaty

PhD Student @ ENS Paris-Saclay

Former members

Kevin E Awoufack

Intern (2023)
single-cell analysis, AI

Antonia Baies

Intern (2023)
model discovery, AI

Rémi Baron

Intern
simulation

Anisse Belhadj

Intern (2022)
bio simulation, C++ development

Johannes Bund

Postdoc @ ENS Paris-Saclay

Azammat Charaf Zadah

Intern
RL, distributed systems

Thomas Chevet

Postdoc (2022/23)
dynamical systems, control theory

Fabricio Cravo

PhD Student (until 2024)
data analysis

Raghda El Shehaby

PhD Student (2022/23)
asynchronous circuit design, robust circuits

Ishan Ganguly

Intern @ MIT

Andrea Garcia

Intern (2023) @ MIT

Gabriel Le Bouder

Postdoc
stochastic cell processes, distributed computing

Vincent Le Dréau

Intern @ U. Paris-Saclay

Letícia Levin Diniz

Intern (2022)
bio simulation, full-stack web development

Luana Martins Ferraz

Intern
genetic circuits

Suhana Nujum G

Intern @ IISER Thiruvananthapuram

Artur Piana

Intern (2022)
microfluidics, embedded systems

Elias Pinter

Intern (2023)
single-cell analysis

Tom Piso

Intern @ ENS Lyon

Gayathri Prakash

Intern (2022/23)
genetic circuits

Abhinav Vinayak Pujar

PhD Student (until 2025)
genetic circuits

Josephine L Ramirez

Intern (2023)
genetic circuits

Thomas Sadigh Rezvani

Intern (2023)
single-cell analysis

Alexander Rinsche

Intern @ TU Wien

Shaunticlair Ruiz

Intern (2023)
stochastic models, cell models

Margarita Shimanskaya

Intern (2023)
stochastic simulation

Berndt Uhlig

Intern (2023)
AI, neural networks

Jessica Vipin

Intern (2023)
AI, verification

Christine Wagner

Intern @ MCI

Zhuofan Xu

PhD Student (until 2025)
AI, data science

Publications

Publications acknowledging the DREAMY grant are also listed on the HAL-ANR portal.

2026

• Victoria Andaur, Janna Burman, Matthias Függer, Bilal Manssouri, Thomas Nowak, Joel Rybicki: Reaching Agreement in Competitive Microbial Systems. Natural Computing, 2026.
• Hagit Attiya, Armando Castañeda, Dhrubajyoti Ghosh, Thomas Nowak: Equivalence and Separation Between Heard-Of and Asynchronous Message-Passing Models. International Colloquium on Structural Information and Communication Complexity (SIROCCO), 2026.
• Benedikt Bollig, Matthias Függer, Thomas Nowak, Paul Zeinaty: Promoting Simple Agents: Ensemble Methods for Event-Log Prediction. arXiv, 2026.
• Benedikt Bollig, Matthias Függer, Thomas Nowak: Provable Coordination for LLM Agents via Message Sequence Charts. arXiv, 2026. To appear at ISoLA 2026.
• Matthieu Borelle, Teodoro Alamo, Sylvain Bertrand, Cristina Stoica, Eduardo F. Camacho: Distributionally robust Kalman filter with outlier detection via Gelbrich ambiguity set. IFAC World Congress, 2026.
• Janna Burman, Ho-Lin Chen, Hsueh-Ping Chen, David Doty, Thomas Nowak, Eric Severson, Chuan Xu: Time-Optimal Self-Stabilizing Leader Election in Population Protocols. Distributed Computing, 2026.
• Fabricio Cravo, Matthias Függer, Thomas Nowak: A quasi-stationary distribution bound for fault analysis in gene regulatory networks. Journal of the Royal Society Interface, 2026.
• Hao Deng, Cristina Stoica Maniu, Mohammed Chadli, Daniel Ossmann: LMI-based Controller Design for Leaky-integrator MIMO Systems. Applications of Modelling and Simulation, 2026.
• Arman Ferdowsi, Matthias Függer, Josef Salzmann, Ulrich Schmid: Accurate closed-form delay formulas for interconnected CMOS gates based on first-order thresholded hybrid systems. Integration, 2026.
• Arman Ferdowsi, Matthias Függer, Thomas Nowak: Efficient Stochastic Trace Generation for Transcription. International Conference on Computational Methods in Systems Biology (CMSB), 2026.
• Matthias Függer, Thomas Nowak: Adding “Verified” Badges to Our Paper, One Lemma at a Time. Bulletin of the EATCS, 2026.
• Matthias Függer, Thomas Nowak: Asymptotic Subspace Consensus in Dynamic Networks. Symposium on Algorithmic Foundations of Dynamic Networks (SAND), 2026.
• Mélanie Pietri, Thomas Rodet, Bruno Le Pioufle, Thomas Nowak, Matthias Függer, Sakina Bensalem: Embedding Response Surfaces in Kinetic Models Predicts Microalgae Growth across Light and Nutrient Gradients. Bioresource Technology, 2026.
• Abhinav Pujar, Anchita Sharma, Manish Kushwaha: Intercellular CRISPRi for Distributed Genetic Circuits. Synthetic Gene Circuits, Methods in Molecular Biology, 2026.
• Zhuofan Xu, Benedikt Bollig, Matthias Függer, Thomas Nowak, Vincent Le Dréau: Centralized Yet Scalable: Revisiting Policy Design for Cooperative Multi-agent Learning. European Conference on Machine Learning and Principles and Practice of Knowledge Discovery in Databases (ECML PKDD), 2026.
• Zhuofan Xu, Benedikt Bollig, Matthias Függer, Thomas Nowak: Deep Reinforcement Learning with Permutation Equivariant Neural Network for Multi-Armed Bandit. International Journal on Artificial Intelligence Tools, 2026.

2025

• Fabricio Cravo, Gayathri Prakash, Matthias Függer, Thomas Nowak: MobsPy: A programming language for biochemical reaction networks. PLOS Computational Biology, 2025.
• Hao Deng, Cristina Stoica, Daniel Ossmann, Mohammed Chadli: Echo State Network Controller Design for a Class of Leaky-Integrator Nonlinear Systems. IEEE Control Systems Letters, 2025.
• Raghda El Shehaby, Matthias Függer, Florian Huemer, Andreas Steininger: Investigating the Effects of Permanent Faults in QDI Circuits: A Formal Perspective. IEEE International Symposium on Asynchronous Circuits and Systems (ASYNC), 2025.
• Raghda El Shehaby, Matthias Függer, Florian Huemer, Andreas Steininger: SeAL: A Provably Complete Fault-Injection Tool for Asynchronous Circuits. IEEE International Conference on Electronics, Circuits and Systems (ICECS), 2025.
• Arman Ferdowsi, Matthias Függer, Thomas Nowak, Ulrich Schmid, Michael Drmota: Faithful dynamic timing analysis of digital circuits using continuous thresholded mode-switched ODEs. Nonlinear Analysis: Hybrid Systems, 2025.
• Matthias Függer, Thomas Nowak, Kerian Thuillier: Distributed computing inspired by biology. Seminars in Cell & Developmental Biology, 2025.
• Maud Hofmann, Farouk Abdo, Olivier Borkowski, Manish Kushwaha: Reconstituting alternative life using the test-bed of cell-free systems. Philosophical Transactions of the Royal Society B, 2025.
• Abhinav Pujar, Amit Pathania, Corbin Hopper, Amir Pandi, Cristian Ruiz Calderón, Matthias Függer, Thomas Nowak, Manish Kushwaha: Phage-mediated intercellular CRISPRi for biocomputation in bacterial consortia. Nucleic Acids Research, 2025.
• Abhinav Pujar, Anchita Sharma, Hadi Jbara, Manish Kushwaha: An M13 phagemid toolbox for engineering tuneable DNA communication in bacterial consortia. bioRxiv, 2025.
• Abhinav Vinayak Pujar: Distributed Biological Circuits in Synthetic Phage-Bacterial Systems. PhD thesis, Université Paris-Saclay, 2025.
• Zhuofan Xu: Permutation Equivariant and Permutation Invariant Reinforcement Learning for Multi-Agent Systems. PhD thesis, Université Paris-Saclay, 2025.

2024

• Lélia Blin, Gabriel Le Bouder, Franck Petit: Optimal Memory Requirement for Self-stabilizing Token Circulation. International Colloquium on Structural Information and Communication Complexity (SIROCCO), 2024.
• Benedikt Bollig, Matthias Függer, Thomas Nowak: A Framework for Streaming Event-Log Prediction in Business Processes. arXiv, 2024.
• Matthieu Borelle, Teodoro Alamo, Cristina Stoica, Sylvain Bertrand, Eduardo F. Camacho: Minimal Gelbrich Distance to Uncorrelation. IEEE Control Systems Letters, 2024.
• Matthieu Borelle, Teodoro Alamo, Cristina Stoica, Sylvain Bertrand, Eduardo F. Camacho: Pearson Coefficient Degradation in a Wasserstein/Gelbrich Ambiguity Set. IEEE Control Systems Letters, 2024.
• Fabricio Cravo, Matthias Függer, Thomas Nowak: An Allee-based distributed algorithm for microbial whole-cell sensors. npj Systems Biology and Applications, 2024.
• Fabricio Cravo: Design of Distributed Biological Circuits. PhD thesis, Université Paris-Saclay, 2024.
• Matthias Függer, Thomas Nowak, Joel Rybicki: Majority Consensus Thresholds in Competitive Lotka-Volterra Populations. ACM Symposium on Principles of Distributed Computing (PODC), 2024.
• Thomas Nowak, Ulrich Schmid, Kyrill Winkler: Topological Characterization of Consensus in Distributed Systems. Journal of the ACM, 2024.
• Zhuofan Xu, Benedikt Bollig, Matthias Függer, Thomas Nowak: Permutation Equivariant Deep Reinforcement Learning for Multi-Armed Bandit. IEEE International Conference on Tools with Artificial Intelligence (ICTAI), 2024.

2023

• Hagit Attiya, Armando Castañeda, Thomas Nowak: Topological Characterization of Task Solvability in General Models of Computation. International Symposium on Distributed Computing (DISC), 2023.
• Johannes Bund, Matthias Függer, Moti Medina: PALS: Distributed Gradient Clocking on Chip. IEEE Transactions on Very Large Scale Integration (VLSI) Systems, 2023.
• Raghda El Shehaby, Matthias Függer, Andreas Steininger: On the Susceptibility of QDI Circuits to Transient Faults. International Conference on Formal Modeling and Analysis of Timed Systems (FORMATS), 2023.
• Arman Ferdowsi, Matthias Függer, Josef Salzmann, Ulrich Schmid: A Hybrid Delay Model for Interconnected Multi-Input Gates. Euromicro Conference on Digital System Design (DSD), 2023.
• Arman Ferdowsi, Matthias Függer, Thomas Nowak, Ulrich Schmid: Continuity of Thresholded Mode-Switched ODEs and Digital Circuit Delay Models. ACM International Conference on Hybrid Systems: Computation and Control (HSCC), 2023.
• Amir Pandi, David Adam, Amir Zare, Van Tuan Trinh, Stefan L. Schaefer, Marie Burt, Björn Klabunde, Elizaveta Bobkova, Manish Kushwaha, Yeganeh Foroughijabbari, Peter Braun, Christoph Spahn, Christian Preußer, Elke Pogge von Strandmann, Helge B. Bode, Heiner von Buttlar, Wilhelm Bertrams, Anna Lena Jung, Frank Abendroth, Bernd Schmeck, Gerhard Hummer, Olalla Vázquez, Tobias J. Erb: Cell-free biosynthesis combined with deep learning accelerates de novo-development of antimicrobial peptides. Nature Communications, 2023.

2022

• Mahnaz Sabeti Azad, Angelo Cardoso Batista, Jean-Loup Faulon, Chase L. Beisel, Jerome Bonnet, Manish Kushwaha: Cell-Free Protein Synthesis from Exonuclease-Deficient Cellular Extracts Utilizing Linear DNA Templates. Journal of Visualized Experiments, 2022.
• Angelo Cardoso Batista, Antoine Levrier, Paul Soudier, Peter L. Voyvodic, Tatjana Achmedov, Tristan Reif-Trauttmansdorff, Angelique DeVisch, Martin Cohen-Gonsaud, Jean-Loup Faulon, Chase L. Beisel, Jerome Bonnet, Manish Kushwaha: Differentially Optimized Cell-Free Buffer Enables Robust Expression from Unprotected Linear DNA in Exonuclease-Deficient Extracts. ACS Synthetic Biology, 2022.
• Da-Jung Cho, Matthias Függer, Corbin Hopper, Manish Kushwaha, Thomas Nowak, Quentin Soubeyran: Distributed computation with continual population growth. Distributed Computing, 2022.
• Fabricio Cravo, Matthias Függer, Thomas Nowak, Gayathri Prakash: MobsPy: A Meta-species Language for Chemical Reaction Networks. International Conference on Computational Methods in Systems Biology (CMSB), 2022.
• Matthias Függer: Computing at the border of abstractions: the power of timed, non-binary, distributed circuits. Habilitation thesis, ENS Paris-Saclay, 2022.
• Matthias Függer, Christoph Lenzen, Ulrich Schmid: On Specifications and Proofs of Timed Circuits. Principles of Systems Design: Essays Dedicated to Thomas A. Henzinger on the Occasion of His 60th Birthday, 2022.
• Joan Hérisson, Thomas Duigou, Melchior du Lac, Kenza Bazi-Kabbaj, Mahnaz Sabeti Azad, Gizem Buldum, Olivier Telle, Yorgo El Moubayed, Pablo Carbonell, Neil Swainston, Valentin Zulkower, Manish Kushwaha, Geoff S. Baldwin, Jean-Loup Faulon: The automated Galaxy-SynBioCAD pipeline for synthetic biology design and engineering. Nature Communications, 2022.
• Amit Pathania, Corbin Hopper, Amir Pandi, Matthias Függer, Thomas Nowak, Manish Kushwaha: A synthetic communication system uncovers extracellular immunity that self-limits bacteriophage transmission. bioRxiv, 2022.
• Paul Soudier, Ana Zúñiga, Thomas Duigou, Peter L. Voyvodic, Kenza Bazi-Kabbaj, Manish Kushwaha, Julie A. Vendrell, Jerome Solassol, Jerome Bonnet, Jean-Loup Faulon: PeroxiHUB: A Modular Cell-Free Biosensing Platform Using H₂O₂ as Signal Integrator. ACS Synthetic Biology, 2022.
• Paul Soudier, Daniel Rodriguez Pinzon, Tristan Reif-Trauttmansdorff, Hassan Hijazi, Maëva Cherrière, Cátia Goncalves Pereira, Doriane Blaise, Maxime Pispisa, Angelyne Saint-Julien, William Hamlet, Melissa Nguevo, Eva Gomes, Sophia Belkhelfa, Anna Niarakis, Manish Kushwaha, Ioana Grigoras: Toehold switch based biosensors for sensing the highly trafficked rosewood Dalbergia maritima. Synthetic and Systems Biotechnology, 2022.

Funding

We are grateful for the funding provided by ANR (grant ANR-21-CE48-0003), CNRS, Digicosme, INRAe, Institut Farman, RFSI, and Université Paris-Saclay.