Description du sujet de thèse

The thesis project is part of an interdisciplinary ANR GlycoDyn research program aimed at developing new therapeutic tools for the selective targeting of pathogenic bacteria by recognition of saccharide epitopes. The main objective is the synthesis of functionalized glycosides and their incorporation into glycosylated polymeric nanovectors capable of targeting bacterial lectins and delivering antibiotics in a controlled manner.
The doctoral student will contribute to the following activities:
Synthesis of functionalized glycosides including saccharide epitopes (Glc, Gal, Fuc, Man) linked to soluble arms (oligoethylene glycol).
Synthesis of functionalized polymers by multi-step organic route, in particular acrylamides carrying aldehyde groups, for integration into polymers via controlled radical polymerization (RAFT, NMP).
Reversible conjugation of these glycosides via dynamic covalent bonds (hydrazones, oximes) to functionalized polymers.
Design of glycosylated, hydrophilic or amphiphilic copolymers, allowing the vectorization of active ingredients.
Study of the structure-activity relationship between polymer architecture, glycosylation density, and binding affinity to bacterial targets.
The thesis will be carried out in co-supervision with Dr. Sébastien Vidal (ICSN) and Dr. Julien Nicolas (IGPS).
Both laboratories are located within the perimeter of the Paris-Saclay University campus, less than 5 kilometers from each other.

Contexte de travail

The Institut de Chimie des Substances Naturelles (ICSN) is a CNRS Research Unit whose research focuses on chemistry and biology. It is part of the University of Paris-Saclay. The ICSN is located on the Gif-sur-Yvette campus and has approximately 120 employees, including 74 permanent staff, spread across 3 buildings. Within the Chemical Biology Department, the recruited employee will join the "Probes and Modulators for Biological Targets" team. He/she will be placed under the hierarchical authority of the team leader and the project will be carried out under the co-direction of Dr. Sébastien Vidal (ICSN) and Dr. Julien Nicolas (IGPS). The laboratory is equipped with all the necessary instruments for the project (HPLC, automatic flash chromatography, microwave synthesis reactor, freeze dryer, rotavap, etc.). Several analytical platforms are present in the institute and provide cutting-edge instruments: NMR (300, 500 MHz), mass spectrometry (LCMS, HRMS) and X-ray diffraction in particular.

The Institut Galien Paris-Saclay (https://www.institut-galien.universite-paris-saclay.fr/) is located on the campus of the University of Paris-Saclay, in the new Henri Moissan building and will benefit from a first-rate academic and research infrastructure, while operating in a rich and scientifically stimulating environment. The IGPS is a joint research unit (UMR 8612) of the CNRS and the University of Paris-Saclay which develops original and innovative research in the fields of micro and nanotechnologies applied to medicine and diagnostics in the health sector.

Contraintes et risques

The project involves the Health and Safety constraints related to the handling of chemicals. The experiments will be carried out in a laboratory equipped with fume hoods.