Centre d'Immunophénomique (PHENOMIN-CIPHE)

PHENOMIN-CIPHE (Centre d'ImmunoPHEnomique) is a UMS (INSERM US12 and Aix-Marseille University/CNRS UMS3367). It is dedicated to the development of KO/KI mice and their extensive and standardised analysis to understand the function of genes involved in immune response in normal and infectious conditions. PHENOMIN-CIPHE, on the strength of its expertise in genetics and mouse immunology, is positioned as a pioneer in multiparametric analysis of the immune system of mutant mice in normal conditions or exposed to risks of infection, by an integration of innovative research and technical knowledge in the field of flow and mass cytometry as well as advanced microscopy.

PHENOMIN-CIPHE develops functional genomic approaches to create preclinical models of the immune system. It creates customisable and high-scale mouse models of human disease or displaying an abnormality (KI, KO mouse models) and it provides a complete phenotyping characterisation of the immune system by polychromatic and mass cytometry measuring more than 50 simultaneous quantitative parameters in standardised conditions.

PHENOMIN-CIPHE has developed a whole set of standardised protocols constituting PHENOMIN-CIPHE "toolbox", which enables to identify with unparalleled precision, the composition and the activation status of myriads of cell populations constituting of the adaptative and innate immune system. By purchasing the mass cytometer CYTOF, PHENOMIN-CIPHE became one of the first European laboratory to provide this service.

Services provided by PHENOMIN-CIPHE are the following :

  • creation of KO (knock-out) and KI (knock-in) innovative mouse models
  • multiparametric analysis of each cell component of the immune system, either in normal conditions or exposed to pathogens, thanks to around 300 quantitative parameters
  • possibility to test the immune system responses in in vivo infectious context (bacterial and viral pathogens)

Technological modules of PHENOMIN-CIPHE include:

  • a module of gene invalidation, of transgenesis and of creation of KI/KO mouse models
  • a module of microinjection and an unit of cryopreservation
  • a module of immunophenotyping
  • a BSL3 laboratory to illustrate in vivo the course of infectious processes
  • a SOPF and A3 animal facility with a housing capacity of 9400 cages

Activities concerning the construction of DNA vectors, production of ES cells and of genetically modified mice, have been certified ISO 9001:2008 by AFNOR in September 2014.

PHENOMIN-CIPHE is the co-founder of PHENOMIN infrastructure, founded by a future investment grant in 2011, together with PHENOMIN-ICS and PHENOMIN-TAAM, enabling a coordination of their complementary activities dedicated to phenogenomic. Through this involvement, PHENOMIN-ICS contributes to European consortium InfraFrontier I3, to the International Mouse Phenotyping Consortium (IMPC) and to the International Knockout Mouse Consortium (IKMC).

Genetic engineering and mouse transgenesis

  • Development of innovative mouse lines by targeted genome modification (knockin-knockout (KI/KO) approaches).
  • Development of humanised mouse models
  • Development of reporting lines enabling tracing and deletion of specific cell populations belonging to the adaptive and innate immune system (dentritic and mast cells)
  • Development of vectors for « multitask » genetic screening
  • Development of mouse models using CRISPR/Cas9 technology

Cryopreservation

  • Microinjection and cryopreservation of established lines

Functional exploration of the immune system

  • Complete phenotyping of the mouse immune system by polychromatic and mass cytometry (CYTOF), thanks to a set of standardised protocols enabling isolation of viable cells from lymphoid and non-lymphoid organs (lung, skin, intestine,...) for labelling using complex ranges of antibodies whose compatibility allows the simultaneous registration of 50 quantitative parameters at least (size, structure, specific antibodies and cell viability).
  • Phenotyping of every cell component of the immune system either in normal conditions or exposed to pathogens, thanks to around 300 quantitative parameters.
  • Cell screening for functional analyses, transcriptomic studies and morphological studies together with imaging
  • Functional analyses of enriched or purified cell populations

Functional exploration in infectious conditions

  • Phenotyping and analysis of the immune system of mutant mice exposed to bacterial and viral pathogens in a BSL3 confined environment
  • Characterisation of immune responses in infected mouse models
  • Testing of vaccines, adjuvants and anti-microbial components
  • Visualisation of the spread of infection by in vivo imaging (two-photon imaging, bioluminescence)

Breeding under SOPF sanitary status

  • Breeding under SOPF sanitary status for development, management of mouse lines and study of mouse models targeting genes involved in the immune response.

Cytometry

  • Flow, mass, spectral cytometry and analysis tools for multiparametric data analysis

    This INSERM training given in English is composed of 2 phases: theoretical courses and technical workshops. It is open to researchers and engineers mastering 6-8 colours cytometry.
    The training implies two partner centers of CELPHEDIA: PHENOMIN-CIPHE and AniRA
    Aims:
    ① Multiparameter flow, mass and image cytometry imply mastering new tools to analyze datasets in order to identify statistically significant variations, but also to efficiently visualize the results. In order to focus on these problematics, state-of-the-art lectures on innovative sampling methods and data analysis pipelines will be presented.
    ② Phase II objective is to initiate participants to fundamental and applied aspects highlighted in Phase I of the workshop. Advanced training on MIC (Multiparametric Image Cytometry) will be dispensed at SFR BioSciences Gerland-Lyon Sud. Practical training on multi-parameter flow, mass and spectral cytometry (respectively MFC, MMC and MSC) will be performed on one single site at CIPHE (Marseille). Finally, a training focused on advanced data analysis pipelines will be performed at FlowCyTech (CEA, Fontenay-aux-Roses).

    Inserm workshop 247 - Registration deadline: June 16
    Workshop 2017 in 2 phases:
    ▪ Theoretical phase I: September 25-27 in Bordeaux
    ▪ Practical phase II: October 2-4 in Fontenay-aux-Roses or October 9-11 in Lyon or October 17-20 in Marseille

    Program

Contribution to regulatory trainings

The objective is to acquire the mandatory qualification to practice animal experimentation in accordance with the transposition of the new European Directive 2010/63.

  • Contribution to regulatory trainings in surgery
    A 28-hour program for people requiring an authorization to perform experiments requiring surgery in accordance with the transposition of the new European Directive 2010/63.

    Formation "CNRS formation entreprises" training: 4 days
    ▪ 1 session in Marseille in 2017: October 17-20
    Description

    Trainings exclusively limited to CNRS employees or non-CNRS employees working in a CNRS unit: 4 days
    ▪ 5 sessions in Marseille in 2017: April 24-27, May 9-12, June 12-15, November 27-30, December 4-7
    Registration procedures

    INSERM training: 4 days
    ▪ 1 session in Marseille in 2017: June 6-9
    Registration

 

  • Contribution to the regulatory trainings to use "rodents" for staff applying experimental procedures (formerly level II)
    A 45-hour training program (a 13-hour basic module + a 32-hour specialized module) for staff required to directly participate to experimentation on animals (technicians).
    "CNRS formation entreprises" in 2017 (5 days): September 25-29 in Marseille
    Training description in Marseille

    Trainings exclusively limited to CNRS employees or non-CNRS employees working in a CNRS unit: 5 days
    ▪ 2 sessions in Marseille in 2017: March 20-24, November 6-10
    Registration

Other trainings

  • Wednesdays of the animal facility
    Trainings and coordination as part of zootechnicians career
  • Courses on animal model and genetic engineering tools for l'UMR-911 of Pharmacy faculty of Aix-Marseille.

PHENOMIN-CIPHE has developed several R&D activities that permitted to maintain a constellation of innovative and branded new technologies in genetic engineering of the mouse genome, immunology and infectiology. A few of those activities are outlined below:

Genome editing

  • Gene engineering tools (‘’One-StrepTagged’’ alleles for interactomics of primary immunocytes, cassette allowing the fast-track construction of multitask alleles, multicolor mice)
  • Gene editing technology tools (TALE nucleases, CRISPR/Cas9)

Immunology

  • Reporter mouse lines for the study of the innate and adaptive immune systems
  • Immunophenotyping panels and assays under normal or infectious (BSL3) conditions (unique combination of antibodies, fluorochromes and user-friendly analysis of data)

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