Stage M2 en bioinformatique structurale

 Stage · Stage M2  · 6 mois    Bac+5 / Master   Biologie intégrée du globule rouge, UMR S_1134 Inserm-Université Paris Cité · Paris (France)  Gratification standard à 590 euros environ

 Date de prise de poste : 16 janvier 2023

Mots-Clés

Modélisation moléculaire, cinétique, interaction ligand-protéine, dynamique moléculaire

Description

Alzheimer's disease is one of the most worrying neurodegenerative diseases of recent years. Among the actors of the disease, amyloid peptides-β lead to a deregulation of the biosynthesis of neurosteroids, drastically reducing their concentration in patients and thus their regenerative properties. It has been demonstrated than neurosteroids stimulate neuroregenerative processes et helps to fight against the disease. Precisely, patients have a high level of endogenous inhibitors of the TSPO protein, a transmembrane protein involved in numerous biological processes, including cholesterol translocation in mitochondria. The protein as also a high tendency to oligomerize, which could be directly related to its function. Furthermore, it appears than cholesterol is the precursor of all steroids, including neurosteroids. Consequently, developing ligands capable of restoring the efficiency and the function of TSPO might be an original way of fighting the disease.

The aim of this internship is therefore to study and understand the impact of different TSPO ligands on the protein behaviour and cholesterol translocation with the mean of in silico tools. Combination of classical and advanced molecular dynamics simulations will allow to measure the impact of ligand binding on the protein and to unravel the molecular mechanisms associated to cholesterol transport. Efforts will be put to a proper estimation of ligands kinetic parameters, since they are crucial to correctly and deeply understand the TSPO will be considered as monomer but also in dimeric state in order to envision all possibilities. Results of this project will be of great importance in order to build an ambitious drug design project targeting TSPO with therapeutic end. This internship is founded by the IDEX Emergence program of Université Paris Cité.

 

Candidature

Procédure : Envoyez un CV et une lettre de motivation à l'adresse mail ci-dessus

Date limite : 1 décembre 2022

Contacts

Julien Diharce

 juNOSPAMlien.diharce@u-paris.fr

Offre publiée le 24 octobre 2022, affichage jusqu'au 1 décembre 2022