Mots-Clés

chemoinformatics drug design structural bioinformatics virtual screening molecular modelling

Description

The Team

The DSIMB team is part of the UMR S_1134 « Integrated Biology of Red Blood Cell » (Inserm- University of Paris) and is led by Dr. Alexandre G. de Brevern. For several years, we developed our research on bioinformatics analysis of protein (e.g. structural alphabet, evolutionary analysis, molecular dynamics simulations, drug design approaches, etc…) and the development of various bioinformatics softwares.

Subject of the internship

Basophils are rare immune cells expressed in the human body. They are involved in several biological functions, such as defence against helminth parasite and connection between the innate and adaptive immune compartments. However, because of their rapid activation in reaction to a wide range of stimuli, they are directly involved in pathogenic processes such as atopic/allergic and inflammatory processes, in both respiratory and skin systems (asthma, rhinitis, urticaria, etc…). It has been shown that the IL3 cytokine is a key protein in the activation of basophils processes and inflammatory response and the team has already characterized deeply the interface between IL-3 and its receptor. Thus, the candidate will study this system in order to identify compounds that can target efficiently the IL-3/IL-3Rα interface. Virtual screening of several chimiotheques will be performed on mouse and human interfaces, followed by molecular dynamics simulations in order to refine the binding pose obtained in our screening protocols. Depending on the progression of the project, drug design approaches will also be employed to optimise the chemical structure of the best hits and by consequence their affinity. The project is financially supported by the ANR (Agence Nationale pour la Recherche, BASIN project, ANR-19-CE17-0021) and involves collaboration with several experimental labs. The position will start in beginning of 2022, with some flexibility on the exacting date, for a duration of 6 months.