Intitulé de l'offre : PhD student in nanomedicine M/W (H/F)
Référence : UMR5305-DANARR-001
Nombre de Postes : 1
Lieu de travail : LYON 07
Date de publication : vendredi 8 septembre 2023
Type de contrat : CDD Doctorant/Contrat doctoral
Durée du contrat : 36 mois
Date de début de la thèse : 15 janvier 2024
Quotité de travail : Temps complet
Rémunération : 2 135,00 € gross monthly
Section(s) CN : Pharmacology, bio-engineering, imaging, biotechnology
Description du sujet de thèse
Mucosal tissues are composed by a specialized epithelium covered by a mucus layer, and are the main portal of entry of most of pathogens. The induction of local (mucosal) immune response is highly desirable in order to effectively prevent mucosal infection and transmission, especially against rapidly emerging pathogens. The presence in the small intestine of Peyer's Patches (PP) as inductive sites of the gut-associated lymphoid tissue (GALT) makes the oral route of administration as a desirable approach to mucosal vaccination. However, the oral vaccine delivery needs to overcome some harsh conditions in the gastrointestinal tract (GIT) such as acid pH, degradation by digestive enzymes, low uptake across mucus layer, and immune tolerance. Lipid-polymer hybrid nanoparticles (NPs) allow the modification of surface properties to overcome the mucosal permeation barriers, enhanced physicochemical stability and drug protection during the transit through the GIT. The objective of SpheOrVac project is to conceive a robust mRNA delivery system able to bypass the GI barrier and to permit a mRNA expression, strong enough to induce a mucosal immune response. Our hypothesis is that by using a combination of dedicated lipids and polymers to form hybrid nanoparticles named Spheroplexes (Sphx), we could gather mRNA vectorization, adjuvant properties and muco-penetrating property in a unique delivery system able to induce a robust and long-lasting mucosal and systemic immune response following oral administration.
Contexte de travail
The project will be carried out within the Laboratory of Tissue Biology and Therapeutic Engineering (LBTI – UMR 5305) in the “Colloidal vectors and targeted therapeutic engineering” team. The team's main projects focus on the design of therapeutic nanoformulations capable of crossing biological barriers with a focus on mucosal transport and immunity. It is important to emphasize that technical staff of the team have strong expertise on nanoparticle mRNA and antigen formulations, in vitro characterization, immunization protocols, serological tests (ELISA, Elispot) and analyzes histological studies dedicated to new vaccine approaches. Likewise, the LBTI benefits from a rich environment within the Lyon – Gerland bio-campus and new installations on the Lyon Santé East campus (main building at Rockefeller) of UCBL1 where this work will be carried out. The recruited person will be required to interact with the team located in Gerland (20 minutes by metro from Rockefeller).
Le poste se situe dans un secteur relevant de la protection du potentiel scientifique et technique (PPST), et nécessite donc, conformément à la réglementation, que votre arrivée soit autorisée par l'autorité compétente du MESR.
Contraintes et risques
The position is exposed to the handling of biological products of human and murine origin. The LBTI follows the Good Laboratory Practices (GLP) guide and strict compliance with the health and safety rules in force. Finally, specific training for the use of equipment and application of techniques used throughout the project are set up by the laboratory.