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Scientific theme and general objectives

Members of the TrEE team combine experimental and in silico interdisciplinary approaches to understand the evolutionary mechanisms leading to adaptation of microorganisms to their environment or to the host they inhabit or infect, and to develop biotechnological applications. We study the dynamics of interactions within the cell, within microbial populations, between microbial populations and their host/environment. Our five research axes constitute a continuum between fundamental and translational research with the aim to advance knowledge and to propose diagnostic and therapeutic innovations.

Research topics

Research Groups

 

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.

Team members
Presentation of team members (introductory sentence)

The team is co-directed by Prof. Bertrand Toussaint and Fabien Pierrel.

Team coordinator(s)

Permanent members

Others members

PhD students

 

Post-doctoral students of the TrEE team :

 

(Coming soon...)

 

 

 

Thesis

TrEE PhD thesis:

Platforms - Resources
EXPERIMENTAL INFECTIOLOGY PLATFORM

PIE

 

Experimental Infectious Diseases Platform

 

   

enumeration

   		MOLECULAR SCREENING VIDEOMICROSCOPIA

 

PIE1 PIE2

Applications areas :

  • Enumeration

  • Invasion

  • Proliferation

  • Interactions with the host

  • Molecular screening

  • Cellular dynamics

PIE3

Aims : evaluate repression or gene expression
in bacteria depending on their environment

 

Place : Jean Roget building
               (UGA - Site Santé)

 

Scientific supervisor :
  Delphine Aldebert

 

 

 

 

PIE4

Aims : evaluate the action of antifungals on the chitin content of yeasts

 

PIE5

Aims: enumeration of parasitic cysts (Dolichos-FITC) in brain crushes

 

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Plateforme de métabolomique par spectrométrie de masse // GExiM

 

Plateforme de métabolomique par spectrométrie de masse

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* Mission de la plateforme

Le laboratoire TIMC dispose d’un accès à un spectromètre de masse haute résolution couplé à une système de chromatographie liquide pour la recherche fondamentale, la recherche translationnelle et clinique en santé, et d’un savoir-faire de l’équipe en analyse de données de métabolomique non ciblée. La plateforme de métabolomique GExiM est une structure technologique hospitalo-universitaire (UGA et CHUGA) fondée en 2018 qui a pour objectif l'étude du métabolome, c'est-à-dire de l'ensemble des métabolites (molécules <1,5 kDa) présents dans un échantillon biologique, pour donner une information diagnostique, pronostique ou thérapeutique ou bien encore d’une meilleur compréhension des mécanismes physiopathologiques des maladies humaines. Elle contribuera à générer des connaissances dans le domaine de la santé, à communiquer aux communautés de scientifiques et au grand public les résultats de la recherche mais aussi à promouvoir la formation des futurs médecins et personnels de santé.
 

* Localisation :

Plateforme de métabolomique GExiM
1er étage Institut de Biologie et de pathologie CHU Grenoble Alpes
9 Boulevard de la Chantourne, 38700 La Tronche

La plateforme GExiM est localisée à l’institut de Biologie et de Pathologie, facilitant ainsi la prise en charge des échantillons clinique par une équipe pluridisciplinaire compétente constituée entre autres de biologistes des hôpitaux et d’ingénieurs.

  • 1er étage, pièce N1-215 :  Pre-analytique et analyse de spectrométrie de masse
  • 1er étage, pièce N1-208 :  Post-analytique. Analyses chimiométriques
    IBP

    * Équipement :

    • Un système de  chromatographie : Vanquich Flex Binary W/O Det
       
    • Un spectromètre de masse : Q Exactive Plus avec enhanced resolution mode. System with Ion Max Source, H-ESI II probe, Chemyx Fusion 100 syringe pump and Rheodyne 6-Port Valve.
      • Gamme de masse : 50 à 6000 Da
      • Résolution de 140,000 à la masse m/z 200 et une vitesse de scan de 1,5 Hz, 17500 la masse m/z 200 à 12 Hz
      • Précision de masse : 5 ppm
      • Sensibilité : sub femtomole pour des peptides, 500fg de Buspirone « on column,
      • Full MS: S/N 100:1 et en mode SIM : 50 fg Buspirone, on column S/N 100:1
         
    • Un générateur d’azote: Nitrogen Generator Genius 1022 (Peak Scientific)

     

    * Personnels :

          - Responsables scientifiques : Pr Bertrand Toussaint et Dr Audrey Le Gouellec      

          - Ingénieurs : Valérie Cunin, Sylvie Michelland et Federica Fiorini     

          - Comité scientifique : Pr M. Seve (Doyen de la Facuté de Pharmacie), Pr P. Faure (Chef de service de Biochimie, Biologie moléculaire, et Toxicologie Environementale), Dr A.E. Hay de Bettignie (UFR de Lyon)

          - Comité de suivi : un coordinateur scientifique, un membre de la DRCI pour le CHUGA, un personnel de Floralis, un personnel de la DGDRIV
     

    * Soutien financier : 

    Cette plateforme a bénéficié d'une aide de l’État gérée par l'Agence Nationale de la Recherche au titre du programme « Investissements d'avenir» portant la référence ANR-15-IDEX-02.

      AURA IDEX UGA CHUGA

     

    * Demande de projet : 

      Principe

       

      CYTOLOGY HISTOLOGY UNIT

       

      University Medical-Technical Unit of Cytology Histology

       

      cyto cyto

       

      The objective of the unit is to provide expertise in the field of morphological analysis through the examination of histological sections but also immunolabels for the detection of specific antigens.
      A quantitative approach can also be taken depending on the type of immunolabelling.

       

      * Place : Bâtiment Jean Roget

      • 1st floor, room 113 :  Impregnation and inclusion in paraffin  -  Colorations  -  Immunolabelling
      • 4th floor, room 410 (air-conditioned) : Paraffin cutting – Cryostat cutting

       

      * Scientific supervisor : Dr Jean Boutonnat PH DACP

      * Technical supervisor : Véronique Curri

       

      Teaching-Training

      The multidisciplinary nature of the research activities of the TrEE team is based on the association of researchers and teacher-researchers attached to a large panel of french CNU sections (64, 65, 44.01, 82, 87 ...) and CNRS commissions (7, 16, 21, 28, 51, ...). This particularity leads logically to the involvement of the team members in teaching and training activities at all levels (from Bachelor's to Doctorate) and in several components of the Grenoble Alpes University (Medicine, Pharmacy, Chemistry-Biology departments) but also of the CNAM Paris. These include courses in microbiology, prokaryotic genetics, molecular and cell biology, infectious diseases, host-pathogen interactions, parasitology, animal biology, differentiation and development, biochemistry, systems biology of biotechnologies, immunology and immuno-oncology.
      In addition, several members of the team have pedagogical and/or collective responsibilities;

      Valorization
      Several biotechnology companies have emerged from the laboratory and are or have been housed in our premises, such as Synthelis, APCure, Pelican Health and Epygone Therapeutics

       

      Contact

      BToussaint@chu-grenoble.fr - Fabien.Pierrel@univ-grenoble-alpes.fr
      Phone: 04 76 63 74 39 -
      Address: Site Santé, Bât Jean Roget, Domaine de la Merci, 38000 La Tronche