The Cell-Free Biofoundry

The Cell-Free Biofoundry : Micalis Institute

Built on solid expertise in biofoundry construction, artificial intelligence, acellular production using alternative strains to E. coli, and strain engineering to optimize acellular efficiency for specific applications, the Micalis Institute is responsible for designing and developing the cell-Free biofoundry.

This biofoundry is dedicated to the production and functional screening of enzymes and therapeutic proteins, as well as the detection of biomarkers (clinical or environmental) using transcriptional and translational devices. To optimize the productivity of acellular systems and reduce variability between batches, the biofoundry standardizes the preparation of extracts by finding the optimal composition of energy buffers and genetic material to maximize transcription and translation processes from linear or plasmid DNA.

Capable of working with extracts from E. coli cells and other strains (purified components, bacteria, yeasts, and mammals), the biofoundry employs new AI methods such as active learning and reinforcement learning to maximize batch-to-batch reproducibility and optimize the transcription process.

In addition to its cell-Free biofoundry, the Micalis institute also works jointly with the Genoscope (UMR8030) to develop the Galaxy-SynBioCAD platform, bringing together around twenty open-source tools under the MIT license, developed by the synthetic biology community.

The platform covers the DBTL cycle on the Galaxy workflow system. The tools use standard formats (InChI, SMARTS, FASTA, SBML, SBOL) to build workflows for metabolic pathway design, enzyme search, cellular network dynamics (FBA), genetic circuit construction, vector assembly using various protocols (Gibson, Golden Gate, BASIC, LRC), and the generation of scripts to control robotic stations for circuit assembly and strain transformation.

The platform is directly connected with omics analysis tools already available on the Galaxy ToolShed, and also includes design of experiments (DoE) tools and can interface with Galaxy deep learning tools. This platform will be integrated into the Paris Biofoundry to develop production and biodetection circuits on cellular or cell-free systems through retrosynthesis approaches combined with artificial intelligence (supervised learning, active learning, reinforcement learning). The platform will be tested across all DBTL cycle stages of the engineering process on the cell-free biofoundry hosted at the Micalis Institute, and will then be deployed to the other three sites of the Paris Biofoundry.

Scientific and technical managers

Jean-Loup Faulon (Director of Micalis Institute, team leader at INRAE)

Joan Herisson (co-leader of Galaxy SynBioCAD platform)

Olivier Borkowski (Synthetic Biology Researcher at INRAE)

Where to find us

Rue de la Manufacture des Toiles de Jouy, Les Metz, Jouy-en-Josas, Versailles, Yvelines, Île-de-France, France métropolitaine, 78350, France

Meet the supervisory institutions of the Micalis Institute Cell-Free Biofoundry