Leader: Jean-Loup Faulon.
This research team is developping retro-synthesis methods to design and build new metabolic networks. Retro-synthesis consists of determining a set of exogenous genes, which once inserted into a host organism, produce a target compound. This method is applied to therapeutic product synthesis by bacterial strains.
Group's website: jfaulon.com
Leader: François Képès.
This team analyzes topology of biological regulatory networks by developping these networks in time (dynamic studies) and in space. The team's recent studies concern the functional organization of the nucleus as well as the genomes evolution and organization. These studies suggest wet experiments, aiming cell regulatory engineering at genomic scale.
The MEGA team analyses how the topology of regulatory biological networks unfolds in time (dynamical studies) and space; this latter point being totally original. We also study links between transcription regulation and DNA replication and segregation, as well as the control of DNA replication by central carbon metabolism.
On the topological level, three original methods have been developed: 1) detection of gene position regularities along chromosomes (Fig. 1); 2) numerical simulation of the folding of a chromosome bound to bifunctional transcription factors, without (Fig. 2) or with (Fig. 3) supercoiling; 3) bioinformatics use of gene position and of gene promoter consensus sequences in order to predict transcriptional interaction maps.
|Figure 1||Figure 2|
Figure 3: a 21kb DNA segment is stretched with a force f=0.8pN, and a supercoiling index sigma=0.033.
The results obtained change our view of nuclear functional organization, as well as of genome evolution and organization. They suggest bench experiments, paving the way to a rational engineering of cell regulation at the genome scale.
Logical approaches of the dynamics of regulatory biological networks are also used to prune models based on spatial information. The same logical approaches are used to study how small biological networks can be embedded into larger networks without altering their dynamical properties.
We carry on this multi-disciplinary work not only on transcriptional networks but also on the dynamics and spatial organization of secretory endomembranes in eukaryotic cells.
Finally, we study how the central carbon metabolism regulates DNA replication. Our results show that this regulatory system involves, in the bacterium Bacillus subtilis, terminal glycolytic reactions and probably conformational modifications of some replication enzymes (Fig. 4).
We currently study the roles of carbon fluxes and of interactions between replication enzymes and metabolic molecules (proteins or metabolites) in this regulatory system.
Leader: Alfonso Jaramillo.
This group works on several aspects of biological networks design and synthetic biology. Theses aspects include transcriptional networks, but also metabolic engineering and systems biology. The team develops computational methods to design bacterial RNA or transcriptional circuits which are then characterized in vivo. Finally, results from experiments feed models and thus close the loop.
The synth-bio group works on the design, synthesis and characterization of synthetic regulatory pathways. Our objective is to systematically construct models from scratch, either of synthetic protein, enzyme or nucleic acid parts, or of genetic devices (oscillators, inverters, amplifiers, digital devices, memory units...), taking special care to: the part characterization; the proteomic/transcriptomic analysis of the E. coli chassis and the re-use of that data in simulations to predict the final behaviour. This approach has the advantages of being quantitative, reproducible and it builds from the current knowledge of the rational design of parts and systems. We will take advantage of our automated computational design methodologies that could be later used with other model systems. We will also benefit from the increasingly available high-throughput data in structural and systems biology. We take advantage of MIT's biobrick database to experimentally construct and characterize our designs and we will incorporate back into the software the necessary design specifications that will arise from the experiments.
The design of more complex genetic devices will pose important questions such as the designability of biological networks, the scalability of the assembly of devices, the most appropriate way to model devices from modular components, or the robustness under noises or under evolutionary pressure. Our aim is to address such questions by extending our computational design methodology while working with concrete projects to be experimentally validated. We will work with an E. coli chassis implementing the different types of genetic devices (sensor, regulatory and metabolic) that would arise from the previous projects.
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Leader: Piet Herdewijn
The ultimate aim of the XENOME team is to design and engineer novel cellular components to elaborate safe GMOs (genetically modified organisms) whose in vivo generation and functionality can be strictly controlled, and which therefore allow the development of new and advanced applications in biotechnology.
Director of Research: Philippe Marliere
Imperatively, such components should be completely hazardless for their surrounding by their inability to genetically spread into existing ecosystems. As the natural genetic code for all life on our planet is solely recognized in the form of DNA and RNA polymers, a robust approach is being development of a truly orthogonal nucleic acid which is chemically distinct from DNA and RNA, but which can harbour structural and/or sequence information that is essential for the viability and phenotype of the cell. Obviously, such a “xeno”-nucleic acid (XNA) will be genetically inert, unless it can be accommodated by artificially evolved enzymes and synthesized from its xeno-nucleotide (XN) precursors. The latter, however, are not present in nature and need to be chemically synthesized and explicitly provided to the cell.