Research Groups

• Metabolomic and Bacteria group
• Respiratory Quinone Group
• Experimental Evolution Group
• Computational Biology's group

Axis #1: Metabolism evolution and engineering

Coordinators: Dr. Audrey le Gouellec & Dr. Fabien Pierrel

The axis “metabolism evolution and engineering” gathers clinicians and researchers who study the evolution of microbial metabolism in connection to their environment and engineer rationally microbes for health benefits. We study metabolic evolutions at different scales by combining experimental and bioinformatics approaches. We employ classical molecular biology and biochemistry but also untargeted metabolomics at the GEMELI-GExiM core facility.

Axis #2: Microbiota evolution and engineering

Coordinators: Dr. Dalil Hannani

We study the impact of gut microbiota on the host, in particular on its  immune system in health and diseases (response to vaccination, cancer,  auto-immunity, acute, and chronic infections). We are developing several strategies to manipulate and optimize the host  gut microbiota, notably through prebiotics or probiotics  administration, or through  bacteria that are engineered on relevant  metabolic pathways. This translational axis extends from preclinical research  to clinical studies aiming at demonstrating the critical role of gut  microbiota metabolic functions in the response to immunotherapy in NSCLC  (Non-Small Lung Cell Carcinoma).

Axis #3: Evolution of the structure and expression of (meta)-genomes

Coordinators: Dr. Ivan Junier & Dr. Thomas Hindré

The composition and organisation of prokaryotic genomes are strongly constrained by natural selection and neutral drift effects. Both mechanisms operate on multiple time scales, from a few generations to billions of generations. As a result, genomes are made of a complex mosaic of both stable and dynamical structures, which contribute to the extraordinary adaptive capacity of microorganisms. In this axis, we study the mechanisms of this plasticity in order to better predict the adaptive responses of microorganisms. To this end, we combine approaches from experimental evolution, molecular biology, comparative genomics, phylogenomics and DNA biophysics.

Axis #4: Microbial evolution toward resistance to antimicrobials

Coordinators: Prof. Muriel Cornet & Dr. Corinne Mercier

The objectives of this research axis include the analysis of evolutionary trajectories leading to the establishment of resistance mechanisms (intrinsic resistance, resistance to low and high doses) and tolerance to antimicrobial agents (antibiotics and antifungals). These studies are conducted in vitro (induction of resistance under antibiotic or antifungal pressure), in natura (patients, environment) and in silico. They use various technologies (microbiology, metagenomics, genetics, cell biology, biochemistry, metabolomics, lipidomics, immunology, epidemiology, multivariate statistical analysis, ...). Basic research allows the development of diagnostic tests and new means of control against targeted infectious agents (Escherichia coli, Pseudomonas aeruginosa, Streptomyces spp, Candida spp, and agents of zoonosis...).

Axe #5: Vectorization and membranes

Coordinators: Dr. Béatrice Schaack & Prof. Jean-Luc Lenormand

The "Vectorization and Membranes" axis focus on the study of membranes and membrane proteins in the context of host-pathogen interactions, the determination of membrane antigenic targets and the influence of the lipid environment on the structure and function of membrane proteins. We use several experimental approaches including the production and the characterization at the biochemical and biophysical levels of extracellular vesicles from different prokaryotic and eukaryotic organisms, the production of membrane proteins in the form of proteoliposomes using cell-free expression systems in the presence of synthetic lipids of different compositions, the use of microscopy techniques (AFM, electron, fluorescence), DLS, impedance spectroscopy (Tethapod) and circular dichroism to name a few. In order to allow a better internalization of certain macromolecules, vectorization systems are used such as cell penetrating peptides and synthetic liposomes. These biotechnological approaches allow a better understanding at the level of pathogen and host cell membranes of certain molecular mechanisms responsible for pathogenesis and provide innovative therapeutic or vaccine solutions. These approaches are used to treat bacteria that are multi-resistant to antibiotics, as well as fungal infections and certain types of cancer.