Missions

Mucins are glycoproteins that protect the intestinal wall from infections and have a significant amount of sialic acids on their surface, such as N-acetylneuraminic acid (Neu5Ac). Neu5Ac serves as a substrate for the growth of specific bacterial species in the microbiota. Several independent studies have shown that excessive hydrolysis of Neu5Ac by bacterial sialidases (SAs) promotes the development of enterobacteria, which play a crucial role in the severity of inflammation. The ANR SIALOBACTER project proposes, for the first time, the development of potent and selective multivalent inhibitors targeting these different families of enzymes. These compounds will allow for a more precise study of their role and could offer an innovative approach for the treatment of chronic inflammatory bowel diseases, particularly by reducing intestinal colonization by enterobacteria.

Within the framework of this ANR project, and following additional funding from the Regional Council of Pays de la Loire, we offer a 12-month funding opportunity for a postdoctoral researcher. The project involves synthesizing analogues of Neu5Ac as inhibitors of SAs and grafting them onto carrier proteins or the surface of microorganisms. This second step will be carried out using an electrochemical bioconjugation reaction recently developed within our group.

For recent publications see:

Click-electrochemistry for the rapid labeling of virus, bacteria, and cell surfaces. 2023. https://chemrxiv.org/engage/chemrxiv/article-details/6401f35737e01856dc159a87

Luminol anchors improve the electrochemical-tyrosine-click labeling of proteins. Chem. Sci., 2021, 12, 15374-15381.

Polyvalent Transition-State Analogues of Sialyl Substrates Strongly Inhibit Bacterial Sialidases. Chem. Eur. J. 2021, 27, 3142-3150.

Activités

-Chemical synthesis and purification of sialidase inhibitors
-Grafting of inhibitors onto proteins or cells using click-electrochemistry
-Writing research reports, presenting results to the group, and at conferences.

Compétences

The candidate holds a Ph.D. in organic chemistry and has an interest in the chemistry/biology interface.

-Previous experience in glycochemistry, bioconjugation reactions, or electrochemistry would be a plus.
-Good communication and writing skills.
-Leadership ability.
-Ability to work in a team and commit to a common project.

Contexte de travail

The CEISAM institute ("Interdisciplinary chemistry: Synthesis, Analysis, Modelling") at the University of Nantes encompasses research activities dedicated to molecular chemistry. The laboratory benefits from cutting-edge equipment for chemical synthesis and analysis, distributed over an area of 3000 m².

Our group has specific expertise in i) designing synthetic multivalent inhibitors of pathogenic lectins and glycosidases, and ii) developing new protein bioconjugation methods for modifying viral, bacterial, and cellular surfaces, as evidenced by the 60 publications and 8 patents published in the field since 2010.
Web link to the research team:
https://ceisam.univ-nantes.fr/en/corail-team/glycochemistry-bioconjugates/

Contraintes et risques

Inherent risks associated with organic synthesis in the laboratory.