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CyberGenetics SIGNED

Cybergenetics: Theory and Design Tools for Biomolecular Control Systems

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Project "CyberGenetics" data sheet

The following table provides information about the project.

Coordinator
EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH 

Organization address
address: Raemistrasse 101
city: ZUERICH
postcode: 8092
website: https://www.ethz.ch/de.html

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Total cost 2˙499˙887 €
 EC max contribution 2˙499˙887 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-ADG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-08-01   to  2022-07-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH CH (ZUERICH) coordinator 2˙499˙887.00

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 Project objective

We propose to develop a new theory and design tools for the estimation and real-time control of living cells. The control systems designed using these tools will precisely and robustly steer the dynamic behavior of living cells in real time to achieve desired objectives. Cells would be controlled either collectively at the population level, or individually as single cells. The control systems achieving this regulation will be realized either on a digital computer that is interfaced with living cells, or using de novo genetic circuits that are introduced into the cells where they are designed to function as molecular control systems. Our methods will explicitly confront the numerous challenges brought about by the special environment of the cell including nonlinearity, stochasticity, cell-to-cell variability, metabolic burden, etc. The theory and methods developed in this project will thus enable the systematic, rational, and effective feedback control of living cells at the gene level, and will lay the foundation for a new corresponding body of knowledge which we call ``Cybergenetics'. It will also open new research directions in the areas of control theory and estimation.

We also propose to design three cybergenetic control systems, each addressing an important application in biotechnology or therapeutics. In the first, the controller will use light and nutrient supply to precisely regulate gene expression and cell growth in E. coli to achieve high protein and low biomass production rates. The second involves multiple feedback controllers regulating in parallel a large number of single stem cells, and leading to their differentiation to desired fates, e.g. beta cells, with potential for therapeutic applications. Finally, we will engineer into living cells dynamic molecular control systems. Such controllers can be used to monitor physiological variables and secrete biological effectors in a feedback fashion for the treatment of diseases like Type 1 diabetes.

 Publications

year authors and title journal last update
List of publications.
2018 Dirk Benzinger, Mustafa Khammash
Pulsatile inputs achieve tunable attenuation of gene expression variability and graded multi-gene regulation
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-05882-2
Nature Communications 9/1 2020-04-24
2020 Melinda Liu Perkins, Dirk Benzinger, Murat Arcak, Mustafa Khammash
Cell-in-the-loop pattern formation with optogenetically emulated cell-to-cell signaling
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-020-15166-3
Nature Communications 11/1 2020-04-24
2020 Daniele Cappelletti, Andrés Ortiz-Muñoz, David F. Anderson, Erik Winfree
Stochastic chemical reaction networks for robustly approximating arbitrary probability distributions
published pages: 64-95, ISSN: 0304-3975, DOI: 10.1016/j.tcs.2019.08.013
Theoretical Computer Science 801 2020-04-24
2019 Stephanie K. Aoki, Gabriele Lillacci, Ankit Gupta, Armin Baumschlager, David Schweingruber, Mustafa Khammash
A universal biomolecular integral feedback controller for robust perfect adaptation
published pages: 533-537, ISSN: 0028-0836, DOI: 10.1038/s41586-019-1321-1
Nature 570/7762 2020-04-24
2020 Ankit Gupta, Marc Manceau, Timothy Vaughan, Mustafa Khammash, Tanja Stadler
The probability distribution of the reconstructed phylogenetic tree with occurrence data
published pages: 110115, ISSN: 0022-5193, DOI: 10.1016/j.jtbi.2019.110115
Journal of Theoretical Biology 488 2020-04-24
2018 Gabriele Lillacci, Yaakov Benenson, Mustafa Khammash
Synthetic control systems for high performance gene expression in mammalian cells
published pages: 9855-9863, ISSN: 0305-1048, DOI: 10.1093/nar/gky795
Nucleic Acids Research 46/18 2019-05-27
2018 Dirk Benzinger, Mustafa Khammash
Pulsatile inputs achieve tunable attenuation of gene expression variability and graded multi-gene regulation
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-05882-2
Nature Communications 9/1 2019-05-27
2018 Corentin Briat, Ankit Gupta, Mustafa Khammash
Antithetic proportional-integral feedback for reduced variance and improved control performance of stochastic reaction networks
published pages: 20180079, ISSN: 1742-5689, DOI: 10.1098/rsif.2018.0079
Journal of The Royal Society Interface 15/143 2019-05-27
2018 Marc Rullan, Dirk Benzinger, Gregor W. Schmidt, Andreas Milias-Argeitis, Mustafa Khammash
An Optogenetic Platform for Real-Time, Single-Cell Interrogation of Stochastic Transcriptional Regulation
published pages: 745-756.e6, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2018.04.012
Molecular Cell 70/4 2019-05-27

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The information about "CYBERGENETICS" are provided by the European Opendata Portal: CORDIS opendata.

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