CE45 - Mathématiques et sciences du numérique pour la biologie et la santé

Optimization and control of the productivity of a bacterial-algal consortium – Ctrl-AB

Submission summary

Communities associating algae and other microorganisms display complex interaction dynamics and give rise to biochemical processes that the single species could not realize in isolation. Suitable design of algal-bacterial consortia thus has tremendous potential for environmental and biotechnological applications of great societal relevance. In-depth exploitation of algal-microbial communities requires careful engineering of the microbial species, quantitative characterization of the community dynamics, the design of microbial community control strategies, and their deployment in automated bioreactors. All of these elements carry challenges at the forefront of current research.

In the Ctrl-AB project, we aim at developing new theoretical analysis and control methods to maximize productivity of lipids by a synthetic algal-bacterial community, and at demonstrating their effectiveness on state-of-the-art experimental platforms, using cutting-edge technologies for the synthesis of molecular sensors and actuators. In our community design, lipid synthesis of the algal population profits from the import of vitamins that are released in the environment by a bacterial population. Bacteria shall be endowed with optogenetic circuits enabling control of vitamin overexpression via light. Despite the mutualistic interactions, which include favorable gaseous exchange between species, growth on common carbon sources results in nontrivial tradeoffs that require careful modulation of interactions by the light control.

Mathematical modelling of the community dynamics must strike an appropriate balance between accuracy and simplicity for later control design. Starting from algal and bacterial metabolic and growth models available to the partners, using new data from dedicated experiments, we will develop accurate mathematical models of the consortium as a whole, and come to a coarse-grained model via a dynamical model reduction approach. Based on this, we will investigate several optimal control problems corresponding to different notions of productivity and yield. Gold-standard control performance will be sought by the Pontryagin optimality principle as a first step. Then, we will develop model-based controllers based on robust and Model Predictive Control techniques, coupled with online algal and bacterial state estimators. Yet, complexity of the system implies possible model inaccuracies and partial knowledge of the dynamics. To circumvent the need for a precise model, we will additionally address data-driven control, an approach essentially unexplored in this context. Finally, our control approaches will be deployed and tested in liter-scale bioreactors, and results compared with lipid biosynthesis via monospecific algal cultures.

The Ctrl-AB project will profit from two experimental platforms. The first is a computer-automated mini-bioreactor platform. Run by our own software ODIN, and further endowed with a light actuation system, it will provide the ideal support for the engineering and testing of optogenetics control in bacteria. The second is a well-established liter-scale experimental platform conceived for the culturing of algae. Further equipped for the co-culturing of algae with the controllable bacterial strains, it will run microbial community modelling and control experiments.

The project is carried out by a strong interdisciplinary consortium providing complementary expertise in the fields of applied mathematics, control theory, synthetic biology, and biotechnology. The coordinator, Jean-Luc Gouzé, is a senior researcher with a long-track record in mathematics and control applied to biology.

Stimulated by the peculiar challenges of the biotech application, the project will spawn advancements in control theory and methods. Symmetrically, the investigation of control methods will advance the use of microbial ecology approaches in biotechnology, with possible breakthroughs of great societal impact.

Project coordination

Jean-Luc GOUZE (Centre de Recherche Inria Sophia Antipolis - Méditerranée)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

LIPHY Laboratoire Interdisciplinaire de Physique
Inria Centre de Recherche Inria Sophia Antipolis - Méditerranée
Inria Grenoble Rhône-Alpes - IBIS Team Centre de Recherche Inria Grenoble - Rhône-Alpes
LOV Laboratoire d'océanographie de Villefranche

Help of the ANR 495,565 euros
Beginning and duration of the scientific project: January 2021 - 48 Months

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