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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - COSY-BIO (Control Engineering of Biological Systems for Reliable Synthetic Biology Applications)

Teaser

Summary

The overarching aim of the COSY-BIO consortium is to develop a theoretical framework and innovative technological tools to engineer reliable biological systems that are robust despite their individual components being not by translating principles of control engineering to molecular and cell biology. Attempts to apply engineering principles to biological processes to understand and build new functions in cells have led to the growing research interdisciplinary community of Synthetic Biology.Currently synthetic circuits can perform only very basic functions thus having a limited impact in biotechnology and biomedicine. Application and adaption of established theories and techniques from conventional control engineering have been hampered by the peculiarities of biological systems, such as cell-to-cell variability, metabolic load, cross-talking and practical realizability. COSY-BIO is laying theoretical and methodological foundations of biomolecular control engineering. COSY-BIO focuses on three major control strategies to impose a desired dynamical behaviour to a biological process of interest, with increasing levels of sophistication and with complementary practical applications: external controllers, embedded controllers and multicellular controllers. This is fundamental to the advancement of current synthetic biology research, especially in the direction of high-impact applications. In the short-term, i.e next 5 year, COSY-BIO can make an impact in biotechnology where engineered microbial cells are used to convert biomass and other feedstock into desired products such as fuels, food and antibiotics. These processes can be made much more efficient in terms of costs and time by engineering external, embedded or multicellular controllers that ensure that the cells behave as desired in the bioreactors to maximise production. In the long-term, in biomedicine, the impact of the future technologies emerging from COSY-BIO lead to major inroads into human cell engineering for therapeutic purposes and regenerative medicine. During the first year of the project we have proceeded on both the theoretical and practical aspects of the projecy, according to the plan. At the theoretical level, we have found a set of guiding principles that allow us to design biological controllers that work reliably and robustly in the cell. At practical level, we have a built an initial prototype of an automated platform able to autonomously perform experiments in bacterial and yeast cells and to build a mathematical model of the biological process of interest, based on the experiment results. We also made progrees on generating the molecular parts needed to engineer controllers in cells and in software tools to simulate their behaviours. At the moment, COSY-BIO is progressing as planned and we do not foresee major hurdles for the next year.

Work performed

The first year of the COSY-BIO project has successfully reached all its milestones and deliverable (D1.1 Comparison of model identification strategies; D6,1 Constructing and testing of reporters of the cell cycle). We do not foresee any major deviations from the project in the next year. Indeed, we made progress both at the theoretical and methodological level, as well as, at the technological and experimental level. The consortium as a whole has published 5 manuscripts in peer-reviewed journals and 3 manuscripts in conference proceedings (details can be found in the References section below). We also organised an Image Analysis Workshop (27 March 2018, Paris) featuring discussion on how to best perform online image segmentation and quantification for real-time feedback control. We also held the Kick-off meeting in November 2017 in Naples and the 1st Annual Meeting (20-21 September 2018, Pozzuoli (Naples)) with the participation of our external advisory board (Prof. Jeff Hasty, UCSD and Prof. Jared Toettcher, Princeton University). As a consortium, we have organised two special sessions on Control Engineering in Biology at the upcoming European Control Conference to be held in Naples in June 2019.

Final results

Control Engineering is a scientific discipline devoted to engineer complex systems and make sure they behave reliably and robustly. For example, airplanes and self-driving cars are equipped with â€œcontrollersâ€ that make sure they track the the correct route at the correct speed, is spite of external disturbances such as wind, rain, traffic, etc. The basic idea driving the COSY-BIO project is to translate Control Engineering principle to engineer bacteria and yeast cells to make useful products with applications to biotechnology and medicine. Attempts to apply engineering principles to biological processes to understand and build new functions in cells have led to the growing research interdisciplinary community of Synthetic Biology. However, application and adaption of established theories and techniques from conventional control engineering have been hampered by the peculiarities of biological systems. As s result, currently synthetic circuits can perform only very basic functions thus having a limited impact in practice. COSY-BIO wants to change this by tackling the problem both at theoretical level and at the practical level. During the first year of the project we have proceeded on both fronts. At the theoretical level, we have found a set of guiding principles that allow us to design biological controllers that work reliably and robustly in the cell. At practical level, we have a built an initial prototype of an automated platform able to autonomously perform experiments in bacterial and yeast cells and to build a mathematical model of the biological process of interest, based on the experiment results. We also made progrees on generating the molecular parts needed to engineer controllers in cells and in software tools to simulate their behaviours. At the moment, COSY-BIO is progressing as planned and we do not foresee major hurdles for the next year.