25/03/2020
The Human Resources Strategy for Researchers

Oral vaccination with Fc-coupled antigens for preventing type 1 diabetes


  • ORGANISATION/COMPANY
    INSERM U1016 - Cochin Institute
  • RESEARCH FIELD
    Medical sciencesMedicine
  • RESEARCHER PROFILE
    First Stage Researcher (R1)
  • APPLICATION DEADLINE
    30/06/2020 00:00 - Europe/Brussels
  • LOCATION
    France › Paris
  • TYPE OF CONTRACT
    Temporary
  • JOB STATUS
    Full-time
  • HOURS PER WEEK
    40
  • OFFER STARTING DATE
    01/07/2020
  • EU RESEARCH FRAMEWORK PROGRAMME
    H2020
  • REFERENCE NUMBER
    IMI2 INNODIA

A postdoctoral position is available to work on a project aimed at developing a new oral vaccination strategy for preventing type 1 diabetes (T1D).

T1D results from the destruction of insulin-producing pancreatic β cells by autoreactive T cells. Antigen-specific strategies are attractive to restore tolerance in T1D due to their selectivity and safety, but have failed so far. Our strategy is to employ β-cell autoantigens coupled with an IgG Fc fragment (Ag-Fc) as tolerogenic vaccines. Our hypothesis is that these Ags-Fc can be transported across the placenta and gut epithelial barriers through the highly expressed neonatal Fc receptor (FcRn), which physiologically delivers maternal IgG to the offspring during fetal life and lactation, thus achieving systemic bioavailability in a non-invasive way. Our proof-of-concept studies using the disease-initiating β-cell Ag preproinsulin (PPI-Fc) demonstrated that maternal vaccination with PPI-Fc during pregnancy protects newborn mice from T1D (Culina et al, Diabetes 2015; Gupta et al, Sci Transl Med 2015). We have now adapted our strategy for oral vaccination, which is non-invasive and easier to translate into T1D prevention trials. Preliminary results show that oral Ag-Fc crosses the intestinal epithelial barrier in an Fc/FcRn-dependent manner and is taken up by antigen-presenting cells.

The post-doctoral fellow will have to evaluate the preventative effect of various forms of oral Ag-Fc vaccines using the non-obese diabetic (NOD) mouse model of T1D, and will identify the therapeutic mechanisms at play and the associated biomarkers: does oral Ag-Fc ‘upgrade’ the selection of autoreactive T cells at the thymic and/or at the peripheral level? Is this effect dependent on elimination of effector T cells and/or on boosting of Tregs? These questions will also be addressed in a new NOD mouse model constitutively expressing the human FcRn that we are generating, allowing us to test different therapeutic windows (neonatal, adult).

This research will provide the preclinical validation and mechanistic understanding of oral Ag-Fc vaccination required to move into T1D prevention trials. To this end, allergy models will be explored in parallel, since they may allow to move faster into human trials because of the short-term clinical outcome in this setting.

 

The Postdoc will design and set up experiments for the progression of the project. He/she will critically analyze the data obtained, generate reports, and use this information to fine-tune the starting hypotheses and design new experiments.

Our Team « T-cell tolerance, biomarkers and therapies in type 1 diabetes » is part of the Cochin Institute located in the center of Paris, 123 boulevard de Port Royal – 75014 Paris, France.

The Cochin Institute is one of the largest biomedical research center in France and provides a multidisciplinary scientific environment and state-of-the-art core facilities. It is affiliated with the French National Institute for Health and Medical Research (INSERM), the University of Paris, the CNRS and the Assistance Publique/Hôpitaux de Paris.

Our team is associated with the Clinical Department of Diabetology and Clinical Immunology of the Cochin Hospital. It belongs to different international consortia such as the European IMI2 Innodia (www.innodia.eu) and the Network for Pancreatic Organ Donors (nPOD; www.jdrfnpod.org).

We offer a stimulating and productive lab environment of young researchers with strong team spirit. This is an excellent career opportunity, as the candidate will have a senior role within the Laboratory and interact with several international collaborators.

Further information. About our Laboratory: www.dearlab.org; about our institute: www.institutcochin.fr.

Applicants should send their CV, letter of motivation and name of 2 references.

Roberto MALLONE & Sylvaine YOU: roberto.mallone@inserm.frsylvaine.you@inserm.fr

 

Required Research Experiences

  • RESEARCH FIELD
    Medical sciencesMedicine
  • YEARS OF RESEARCH EXPERIENCE
    1 - 4
  • RESEARCH FIELD
    Biological sciencesBiology
  • YEARS OF RESEARCH EXPERIENCE
    1 - 4

Offer Requirements

  • REQUIRED LANGUAGES
    ENGLISH: Excellent

Skills/Qualifications

  • Knowledge: A strong expertise in immunology, multiparametric flow cytometry, cell culture and animal experimentation is preferred. Fluent English, written and spoken. Applications not fulfilling these criteria will not be considered.
  • Professional skills: The candidate must be highly motivated and use creative thinking in the resolution of scientific questions. He/she will be able to adapt to rapidly evolving technologies and will have a broad interest for biomedical research. He/she will need to give proof of independent thinking and writing skills and capacity to undertake responsibility as project leader. It is essential that the candidate can work autonomously and as part of a team.
  • Education: MD/PhD or PhD in immunology/biological sciences.

Map Information

Job Work Location Personal Assistance locations
Work location(s)
1 position(s) available at
INSERM U1016 - Cochin Institute
France
Paris
75014
Groupe Hospitalier Cochin-Port-Royal, Bâtiment Cassini - 123, boulevard de Port-Royal

EURAXESS offer ID: 508190

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