New granted project

Design, characterization and optimal tuning of synthetic biocircuits for bioproduction with control of the metabolic load (SynBioControl)

The project SynBioControl has been granted by the MINECO/AEI/FEDER,UE  (Grant DPI2017-82896-C2-1-R). New The biotech industry of the immediate future will integrate complex synthetic genetic circuits into microorganisms used as cell factories to produce proteins and metabolites of industrial importance. To this end, it has to deal with several critical problems that currently limit the applicability of synthetic biology: the rational design of synthetic genetic circuits of increasing complexity, their experimental characterization and robust tuning, and their industrial scaling. One of the main factors hindering the solution of these problems is the modification of the expected behavior of the circuits designed as a consequence of metabolic and genetic load of the cell caused by usage of shared time-varying cellular resources. Managing these phenomena requires the redesign of the circuits and the addition of additional feedback control mechanisms in order to maintain the specified design behavior. In this line SynBioControl adopts synthetic biology as a discipline of engineering, and emphasizes the application of engineering principles and methodologies via strategies of feedback control, computational optimization and multivariate analysis.

The project focuses on a practical challenge and two related general objectives:

- General Practical Challenge: Design and implementation of feedback control mechanisms of protein and metabolite expression with consideration of the effects of metabolic and genetic load.

- Methodological Objective 1: Development of methods of structural design, analysis and robust parametric tuning of synthetic control genetic circuits through multiobjective optimization.

- Methodological Objective 2: Development of data analytics methods and grey models with application to scaling-up from the laboratory to the pre-industrial bioreactor.

Two objectives will be considered transversal to the previous ones:

- Transversal Objective 1: Contribution to the conversion of Synthetic Biology into an engineering, making the modeling and design process more systematic (standardized), modular, predictable, and robust, with an emphasis on the development of methodologies that can be applied in an effective way in the practical environment of a standard industrial biotechnology laboratory.

- Transversal Objective 2: Implementation of open source software tools and devices or biological parts (biobricks) of public access, facilitating the dissemination of Synthetic Biology as an area of engineering.

In SynBioControl we will make use of essential enabling technologies (feedback control, computational optimization, and multivariate analysis) coupled with metabolic engineering and DNA synthesis and assembly, will provide the right solutions.

To achieve its objectives, SynBioControl integrates an academic group of systems engineering, control and statistics specialized in modeling and control of bioprocesses, systems and synthetic biology, multivariate statistics, monitoring, scaling of processes and analysis of omics data (SB2CLab/GIEM-UPV) and a chemical engineering group specialized in bioprocess engineering, including modelling and optimization in systems and synthetic biology (IIM-CSIC). In addition, the project includes Biopolis S.L. (http://www.biopolis.es/es/inicio/), a Valencian biotechnology company leader in Spain, belonging to the ADM group, and provider of R & D and production services for the agro-food, pharmaceutical, chemical and energy industries.