DYNAMICS OF THE MICROTUBULE CYTOSKELETON: STRUCTURAL BIOINFORMATICS of spastin in interaction with ITS partners

Type de poste
Dates
Durée du poste
Contrat renouvelable
Contrat non renouvelable
Date de prise de fonction
Date de fin de validité de l'annonce
Localisation
Adresse

<p>Université d&#39;Evry-Val d&#39;Essonne</p><p>Bât. Maupertuis</p><p>1 rue du Père Jarlan</p><p>Evry</p>
91000 Evry
France

Contacts
R. Charbel MAROUN
Email du/des contacts
charbel.maroun@inserm.fr
Description

<p>OFFRE POURVUE</p><p>&nbsp;</p><p>The understanding of the dynamics of microtubules and the role of the protein partners that regulate the cytoskeleton remains incomplete. A better knowledge will enlighten fundamental processes of critical importance in biology, such as cell cycle and neurodegeneration). Spastin (Spastic ParapleGia 4, SPG4) is a ubiquitous protein involved in several microtubule-dependent functions such as intracellular membrane traffic, cytokinesis and endoplasmic reticulum morphogenesis. Mutations of SPG4 induce hereditary Human Spastic Paraplegias (HSP) -genetic disorders characterized by progressive lower limb spasticity and weakness. At the cellular level this disease is characterized by a degeneration of cortico-spinal tract axons. To date only symptomatic treatments partially improving spasticity are available for HSP patients -no preventive or curative treatments exist; thus, the importance of understanding the molecular mechanisms regulated by spastin underlying axon maintenance and function. In our laboratory an interdisciplinary approach (NMR, cell and molecular biology, optical and video microscopy, structural bioinformatics) is used for studying the physiological and pathological role of spastin and its regulation by molecular partners, several of which have been recently identified by us. The goal of this research project is to analyze, via structural bioinformatics (molecular modeling and simulation), the 3D structure and dynamics of the biomolecular interactions between different spastin domains and known and unknown promising molecular partners, so as to understand the mechanism of action of spastin and its pathogenic mutants, leading eventually to HSP-directed therapy.</p><p>&nbsp;</p><p>Ecole Doctorale Structure et dynamique des systèmes vivants (SDSV), Université Paris-Saclay</p><br/>
Laboratoire: UMR INSERM U1204/UEVE Structure et activité des biomolécules normales et pathologiques