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.
Début/Biginning: June 1st, 2020
Durée du contrat/Length of contract: 12-month contract, renewable yearly for up to 3 years.
Structure employeur/organization INSERM
Applicants should send their CV, letter of motivation and name of 2 references.
Envoyez votre CV, lettre de motivation et deux contacts de recommandations à :Meer informatie
|Titel||Post Doc position - Oral vaccination with Fc-coupled antigens for preventing type 1 diabetes|
|Job location||22 rue Méchain, 75014 Paris|
|Gepubliceerd||maart 24, 2020|
|Vakgebieden||Biogeneeskunde,   Klinische wetenschappen,   Pathologie,   Immunologie,   Celbiologie,   Endocrinologie  |