Control Engineering of Biological Systems for Reliable Synthetic Biology Applications

Project Information

COSY-BIO

Grant agreement ID: 766840

DOI 10.3030/766840

Project closed

EC signature date 24 August 2017

Start date 1 October 2017

End date 31 March 2021

Funded under

• EXCELLENT SCIENCE - Future and Emerging Technologies (FET)

Total cost € 2 996 856,25

EU contribution € 2 975 345,00

Coordinated by

FONDAZIONE TELETHON ETS
Italy

Deliverables

Other (4)

Website and intranet portal

Website and intranet portal put online

Official Logo of COSY-BIO
Software tool suite
Software tool for model identification

Open Research Data Pilot (3)

Data Management plan
Final Dissemination and exploitation report
Detailed Dissemination and Exploitation plan

Demonstrators, pilots, prototypes (2)

Constructing and testing of reporters of the cell cycle
Optimal Experimental Design and BioModel Identification platform

Documents, reports (5)

Financial/Scientific report RP2
Comparison of model identification strategies
Modelling circuit/chassis interactions in high load conditions
Report of completed communication activity
Report on robust and adaptive control

Publications

Peer reviewed articles (28)

Self-adaptive biosystems through tunable genetic parts and circuits

Author(s): Vittorio Bartoli, Mario di Bernardo, Thomas E. Gorochowski
Published in: Current Opinion in Systems Biology, Issue 24, 2020, Page(s) 78-85, ISSN 2452-3100
Publisher: Elsevier
DOI: 10.1016/j.coisb.2020.10.006

Automatic synchronisation of the cell cycle in budding yeast through closed-loop feedback control

Author(s): Giansimone Perrino, Sara Napolitano, Francesca Galdi, Antonella La Regina, Davide Fiore, Teresa Giuliano, Mario di Bernardo, Diego di Bernardo
Published in: Nature Communications, Issue 12/1, 2021, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-021-22689-w

ChipSeg: An Automatic Tool to Segment Bacterial and Mammalian Cells Cultured in Microfluidic Devices

Author(s): Irene de Cesare, Criseida G. Zamora-Chimal, Lorena Postiglione, Mahmoud Khazim, Elisa Pedone, Barbara Shannon, Gianfranco Fiore, Giansimone Perrino, Sara Napolitano, Diego di Bernardo, Nigel J. Savery, Claire Grierson, Mario di Bernardo, Lucia Marucci
Published in: ACS Omega, Issue 6/4, 2021, Page(s) 2473-2476, ISSN 2470-1343
Publisher: ACS Omega
DOI: 10.1021/acsomega.0c03906

In Vivo Feedback Control of an Antithetic Molecular-Titration Motif in Escherichia coli Using Microfluidics

Author(s): Barbara Shannon, Criseida G. Zamora-Chimal, Lorena Postiglione, Davide Salzano, Claire S. Grierson, Lucia Marucci, Nigel J. Savery, Mario di Bernardo
Published in: ACS Synthetic Biology, Issue 9/10, 2020, Page(s) 2617-2624, ISSN 2161-5063
Publisher: American Chemical Society
DOI: 10.1021/acssynbio.0c00105

Furthering genome design using models and algorithms

Author(s): Joshua Rees-Garbutt, Jake Rightmyer, Jonathan R. Karr, Claire Grierson, Lucia Marucci
Published in: Current Opinion in Systems Biology, Issue 24, 2020, Page(s) 120-126, ISSN 2452-3100
Publisher: Elsevier Ltd
DOI: 10.1016/j.coisb.2020.10.007

Analysis and Control of Genetic Toggle Switches Subject to Periodic Multi-Input Stimulation

Author(s): Davide Fiore, Agostino Guarino, Mario di Bernardo
Published in: IEEE Control Systems Letters, Issue 3/2, 2019, Page(s) 278-283, ISSN 2475-1456
Publisher: IEEE
DOI: 10.1109/lcsys.2018.2868925

Computer-Aided Whole-Cell Design: Taking a Holistic Approach by Integrating Synthetic With Systems Biology

Author(s): Lucia Marucci, Matteo Barberis, Jonathan Karr, Oliver Ray, Paul R. Race, Miguel de Souza Andrade, Claire Grierson, Stefan Andreas Hoffmann, Sophie Landon, Elibio Rech, Joshua Rees-Garbutt, Richard Seabrook, William Shaw, Christopher Woods
Published in: Frontiers in Bioengineering and Biotechnology, Issue 8, 2020, ISSN 2296-4185
Publisher: Frontiers
DOI: 10.3389/fbioe.2020.00942

A universal biomolecular integral feedback controller for robust perfect adaptation

Author(s): Stephanie K. Aoki, Gabriele Lillacci, Ankit Gupta, Armin Baumschlager, David Schweingruber, Mustafa Khammash
Published in: Nature, Issue 570/7762, 2019, Page(s) 533-537, ISSN 0028-0836
Publisher: Nature Publishing Group
DOI: 10.1038/s41586-019-1321-1

Multicellular Feedback Control of a Genetic Toggle-Switch in Microbial Consortia

Author(s): Davide Fiore, Davide Salzano, Enric Cristobal-Coppulo, Josep M. Olm, Mario di Bernardo
Published in: IEEE Control Systems Letters, Issue 5/1, 2021, Page(s) 151-156, ISSN 2475-1456
Publisher: IEEE
DOI: 10.1109/lcsys.2020.3000954

Approximations of Countably Infinite Linear Programs over Bounded Measure Spaces

Author(s): Juan Kuntz, Philipp Thomas, Guy-Bart Stan, Mauricio Barahona
Published in: SIAM Journal on Optimization, Issue 31/1, 2021, Page(s) 604-625, ISSN 1052-6234
Publisher: Society for Industrial and Applied Mathematics
DOI: 10.1137/19m1268847

The Exit Time Finite State Projection Scheme: Bounding Exit Distributions and Occupation Measures of Continuous-Time Markov Chains

Author(s): Juan Kuntz, Philipp Thomas, Guy-Bart Stan, Mauricio Barahona
Published in: SIAM Journal on Scientific Computing, Issue 41/2, 2019, Page(s) A748-A769, ISSN 1064-8275
Publisher: Society for Industrial and Applied Mathematics
DOI: 10.1137/18m1168261

Cheetah: A Computational Toolkit for Cybergenetic Control

Author(s): Elisa Pedone, Irene de Cesare, Criseida G. Zamora-Chimal, David Haener, Lorena Postiglione, Antonella La Regina, Barbara Shannon, Nigel J. Savery, Claire S. Grierson, Mario di Bernardo, Thomas E. Gorochowski, Lucia Marucci
Published in: ACS Synthetic Biology, Issue 10/5, 2021, Page(s) 979-989, ISSN 2161-5063
Publisher: American Chemical Society
DOI: 10.1021/acssynbio.0c00463

Stationary Distributions of Continuous-Time Markov Chains: A Review of Theory and Truncation-Based Approximations

Author(s): Juan Kuntz, Philipp Thomas, Guy-Bart Stan, Mauricio Barahona
Published in: SIAM Review, Issue 63/1, 2021, Page(s) 3-64, ISSN 0036-1445
Publisher: Society for Industrial and Applied Mathematics
DOI: 10.1137/19m1289625

A network model of Italy shows that intermittent regional strategies can alleviate the COVID-19 epidemic

Author(s): Fabio Della Rossa, Davide Salzano, Anna Di Meglio, Francesco De Lellis, Marco Coraggio, Carmela Calabrese, Agostino Guarino, Ricardo Cardona-Rivera, Pietro De Lellis, Davide Liuzza, Francesco Lo Iudice, Giovanni Russo, Mario di Bernardo
Published in: Nature Communications, Issue 11/1, 2020, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-020-18827-5

Face coverings and respiratory tract droplet dispersion

Author(s): Lucia Bandiera, Geethanjali Pavar, Gabriele Pisetta, Shuji Otomo, Enzo Mangano, Jonathan R. Seckl, Paul Digard, Emanuela Molinari, Filippo Menolascina, Ignazio Maria Viola
Published in: Royal Society Open Science, Issue 7/12, 2020, Page(s) 201663, ISSN 2054-5703
Publisher: Royal Society Publishing
DOI: 10.1098/rsos.201663

Tools for engineering coordinated system behaviour in synthetic microbial consortia

Author(s): Nicolas Kylilis, Zoltan A. Tuza, Guy-Bart Stan, Karen M. Polizzi
Published in: Nature Communications, Issue 9/1, 2018, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-018-05046-2

An Optogenetic Platform for Real-Time, Single-Cell Interrogation of Stochastic Transcriptional Regulation

Author(s): Marc Rullan, Dirk Benzinger, Gregor W. Schmidt, Andreas Milias-Argeitis, Mustafa Khammash
Published in: Molecular Cell, Issue 70/4, 2018, Page(s) 745-756.e6, ISSN 1097-2765
Publisher: Cell Press
DOI: 10.1016/j.molcel.2018.04.012

On-Line Optimal Input Design Increases the Efficiency and Accuracy of the Modelling of an Inducible Synthetic Promoter

Author(s): Lucia Bandiera, Zhaozheng Hou, Varun Kothamachu, Eva Balsa-Canto, Peter Swain, Filippo Menolascina
Published in: Processes, Issue 6/9, 2018, Page(s) 148, ISSN 2227-9717
Publisher: MDPI AG
DOI: 10.3390/pr6090148

Synthetic control systems for high performance gene expression in mammalian cells

Author(s): Gabriele Lillacci, Yaakov Benenson, Mustafa Khammash
Published in: Nucleic Acids Research, Issue 46/18, 2018, Page(s) 9855-9863, ISSN 0305-1048
Publisher: Oxford University Press
DOI: 10.1093/nar/gky795

Characterization and mitigation of gene expression burden in mammalian cells

Author(s): Timothy Frei, Federica Cella, Fabiana Tedeschi, Joaquín Gutiérrez, Guy-Bart Stan, Mustafa Khammash, Velia Siciliano
Published in: Nature Communications, Issue 11/1, 2020, Page(s) 4641, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-020-18392-x

Synchronisation of yeast cell cycle through quorum sensing coupling

Author(s): Giansimone Perrino, Diego di Bernardo
Published in: IFAC-PapersOnLine, Issue 53/2, 2020, Page(s) 16779-16784, ISSN 2405-8963
Publisher: Elsevier, IFAC Publisher
DOI: 10.1016/j.ifacol.2020.12.1143

Autonomous and Assisted Control for Synthetic Microbiology

Author(s): Alvaro Banderas, Matthias Le Bec, Céline Cordier, Pascal Hersen
Published in: International Journal of Molecular Sciences, Issue 21/23, 2020, Page(s) 9223, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms21239223

Regulation of Gene Expression and Signaling Pathway Activity in Mammalian Cells by Automated Microfluidics Feedback Control

Author(s): Lorena Postiglione, Sara Napolitano, Elisa Pedone, Daniel L. Rocca, Francesco Aulicino, Marco Santorelli, Barbara Tumaini, Lucia Marucci, Diego di Bernardo
Published in: ACS Synthetic Biology, Issue 7/11, 2018, Page(s) 2558-2565, ISSN 2161-5063
Publisher: American Chemical Society
DOI: 10.1021/acssynbio.8b00235

Quantitative Characterization of α-Synuclein Aggregation in Living Cells through Automated Microfluidics Feedback Control

Author(s): Giansimone Perrino, Cathal Wilson, Marco Santorelli, Diego di Bernardo
Published in: Cell Reports, Issue 27/3, 2019, Page(s) 916-927.e5, ISSN 2211-1247
Publisher: Cell Press
DOI: 10.1016/j.celrep.2019.03.081

Balancing Cell Populations Endowed with a Synthetic Toggle Switch via Adaptive Pulsatile Feedback Control

Author(s): Agostino Guarino, Davide Fiore, Davide Salzano, Mario di Bernardo
Published in: ACS Synthetic Biology, Issue 9/4, 2020, Page(s) 793-803, ISSN 2161-5063
Publisher: American Chemical Society
DOI: 10.1021/acssynbio.9b00464

A low-cost, open-source Turbidostat design for in-vivo control experiments in Synthetic Biology

Author(s): Agostino Guarino, Barbara Shannon, Lucia Marucci, Claire Grierson, Nigel Savery, Mario di Bernardo
Published in: IFAC-PapersOnLine, Issue 52/26, 2019, Page(s) 244-248, ISSN 2405-8963
Publisher: Elsevier Ltd
DOI: 10.1016/j.ifacol.2019.12.265

A finite state projection method for steady-state sensitivity analysis of stochastic reaction networks

Author(s): Patrik Dürrenberger, Ankit Gupta, Mustafa Khammash
Published in: The Journal of Chemical Physics, Issue 150/13, 2019, Page(s) 134101, ISSN 0021-9606
Publisher: American Institute of Physics
DOI: 10.1063/1.5085271

Tunable genetic devices through simultaneous control of transcription and translation

Author(s): Vittorio Bartoli, Grace A. Meaker, Mario di Bernardo, Thomas E. Gorochowski
Published in: Nature Communications, Issue 11/1, 2020, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-020-15653-7

Conference proceedings (10)

Towards feedback control of the cell-cycle across a population of yeast cells

Author(s): Giansimone Perrino, Davide Fiore, Sara Napolitano, Mario di Bernardo, Diego di Bernardo
Published in: 2019 18th European Control Conference (ECC), 2019, Page(s) 2644-2650, ISBN 978-3-907144-00-8
Publisher: IEEE
DOI: 10.23919/ecc.2019.8796301

Cybergenetics: Theory and Methods for Genetic Control System

Author(s): M. Khammash, M. Di Bernardo, D. Di Bernardo
Published in: 2019 IEEE 58th Conference on Decision and Control (CDC), 2019, Page(s) 916-926, ISBN 978-1-7281-1398-2
Publisher: IEEE
DOI: 10.1109/cdc40024.2019.9030209

Optimal Parameter Tuning of Feedback Controllers with Application to Biomolecular Antithetic Integral Control

Author(s): Maurice Filo, Mustafa Khammash
Published in: 2019 IEEE 58th Conference on Decision and Control (CDC), 2019, Page(s) 951-957, ISBN 978-1-7281-1398-2
Publisher: IEEE
DOI: 10.1109/cdc40024.2019.9029430

Quantification of loading effects in interconnections of stochastic reaction networks

Author(s): Ankit Gupta, Patrik Durrenberger, Mustafa Khammash
Published in: 2019 18th European Control Conference (ECC), 2019, Page(s) 2165-2170, ISBN 978-3-907144-00-8
Publisher: IEEE
DOI: 10.23919/ecc.2019.8796155

Can optimal experimental design serve as a tool to characterize highly non-linear synthetic circuits?

Author(s): Maxim Kryukov, Arthur Carcano, Gregory Batt, Jakob Ruess
Published in: 2019 18th European Control Conference (ECC), 2019, Page(s) 1176-1181, ISBN 978-3-907144-00-8
Publisher: IEEE
DOI: 10.23919/ecc.2019.8796209

Ratiometric control for differentiation of cell populations endowed with synthetic toggle switches

Author(s): Davide Salzano, Davide Fiore, Mario di Bernardo
Published in: 2019 IEEE 58th Conference on Decision and Control (CDC), 2019, Page(s) 927-932, ISBN 978-1-7281-1398-2
Publisher: IEEE
DOI: 10.1109/cdc40024.2019.9029592

Optimal control of an artificial microbial differentiation system for protein bioproduction

Author(s): Elise Weill, Virgile Andreani, Chetan Aditya, Pierre Martinon, Jakob Ruess, Gregory Batt, Frederic Bonnans
Published in: 2019 18th European Control Conference (ECC), 2019, Page(s) 2663-2668, ISBN 978-3-907144-00-8
Publisher: IEEE
DOI: 10.23919/ecc.2019.8795858

In-silico feedback control of a MIMO synthetic Toggle Switch via Pulse-Width Modulation

Author(s): Agostino Guarino, Davide Fiore, Mario Di Bernardo
Published in: 2019 18th European Control Conference (ECC), 2019, Page(s) 680-685, ISBN 978-3-907144-00-8
Publisher: IEEE
DOI: 10.23919/ecc.2019.8795642

Optimally designed vs intuition-driven inputs: the study case of promoter activity modelling

Author(s): L. Bandiera, V. Kothamachu, E. Balsa-Canto, P. S. Swain, F. Menolascina
Published in: 2018 IEEE Conference on Decision and Control (CDC), 2018, Page(s) 1880-1885, ISBN 978-1-5386-1395-5
Publisher: IEEE
DOI: 10.1109/cdc.2018.8618920

Characterization of Biologically Relevant Network Structures form Time-series Data

Author(s): Zoltan A. Tuza, Guy-Bart Stan
Published in: 2018 IEEE Conference on Decision and Control (CDC), 2018, Page(s) 1089-1095, ISBN 978-1-5386-1395-5
Publisher: IEEE
DOI: 10.1109/cdc.2018.8619360

Other (5)

Exploring the Dynamics of Nonlinear Biochemical Systems using Control-Based Continuation

Author(s): Brandon Gomes, Irene de Cesare, Agostino Guarino, Mario di Bernardo, Ludovic Renson, Lucia Marucci
Published in: 2019
Publisher: biorxiv
DOI: 10.1101/695866

A Class of Simple Biomolecular Antithetic Proportional-Integral-Derivative Controllers

Author(s): Maurice Filo, Mustafa Khammash
Published in: 2021
Publisher: biorxiv
DOI: 10.1101/2021.03.21.436342;

Tutorial of numerical continuation and bifurcation theory for systems and synthetic biology

Author(s): Mark Blyth, Ludovic Renson, Lucia Marucci
Published in: arxiv, 2020
Publisher: arxiv
DOI: 10.5281/zenodo.4835824

Feedback control promotes synchronisation of the cell-cycle across a population of yeast cells

Author(s): Giansimone Perrino, Davide Fiore, Sara Napolitano, Francesca Galdi, Antonella La Regina, Mario di Bernardo, and Diego di Bernardo
Published in: biorXiv, 2019
Publisher: biorXiv
DOI: 10.1101/590844

Self-adaptive Biosystems Through Tunable Genetic Parts and Circuits

Author(s): Vittorio Bartoli, Mario di Bernardo, Thomas E. Gorochowski
Published in: 2020
Publisher: Preprints
DOI: 10.20944/preprints202007.0751.v2

Book chapters (1)

Minimal Genome Design Algorithms Using Whole-Cell Models

Author(s): Joshua Rees-Garbutt, Oliver Chalkley, Claire Grierson, Lucia Marucci
Published in: Computational Methods in Synthetic Biology, Issue 2189, 2021, Page(s) 183-198, ISBN 978-1-0716-0821-0
Publisher: Springer US
DOI: 10.1007/978-1-0716-0822-7_14