General information
Organisation
The French Alternative Energies and Atomic Energy Commission (CEA) is a key player in research, development and innovation in four main areas :
• defence and security,
• nuclear energy (fission and fusion),
• technological research for industry,
• fundamental research in the physical sciences and life sciences.
Drawing on its widely acknowledged expertise, and thanks to its 16000 technicians, engineers, researchers and staff, the CEA actively participates in collaborative projects with a large number of academic and industrial partners.
The CEA is established in ten centers spread throughout France
Reference
SL-DRF-24-0527
Direction
DRF
Thesis topic details
Category
Life Sciences
Thesis topics
Molecular dynamics and disorder in the viral replication machinery of SARS CoV 2
Contract
Thèse
Job description
The nucleoprotein (N) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for genome replication, encapsidating the viral genome and regulating gene transcription. The central disordered domain is essential to the function of this highly dynamic protein, containing a number of important mutations that are responsible for enhanced viral fitness, and comprising a region that is hyperphosphorylated during the viral cycle. NMR spectroscopy is the tool of choice for studying the conformational behaviour of intrinsically disordered proteins, an abundant class of proteins that are functional in their disordered form. They represent 40% of the proteome and are too dynamic to be studied by crystallography or electron microscopy. The host lab has developed a large number of unique NMR-based tools to help understand the function of this class of proteins at atomic resolution. We will use NMR, paramagnetic NMR, small angle scattering, single molecule FRET and electron microscopy, in combination with molecular dynamics simulation, to describe the interactions of N with viral partner proteins and viral RNA. Post-translational modification, in particular phosphorylation, is thought to play an important functional role, that remains poorly understood, we will investigate the impact of phosphorylation on conformational dynamics and relate this to modifications in function. The results will be correlated with light end electron microscopy, carried out in collaboration.
University / doctoral school
Ecole Doctorale de Physique de Grenoble (EdPHYS)
Université Grenoble Alpes
Thesis topic location
Site
Grenoble
Requester
Position start date
01/10/2024
Person to be contacted by the applicant
BLACKLEDGE Martin martin.blackledge@ibs.fr
CEA
DRF/IRIG//IBS
Protein Dynamics and Flexibility
Institut de Biologie Structurale
CAMPUS EPN
71 avenue des Martyrs
CS 10090
38044 Grenoble Cedex 9
France
0457428554
Tutor / Responsible thesis director
BLACKLEDGE Martin martin.blackledge@ibs.fr
CEA
DRF/IRIG//IBS
Protein Dynamics and Flexibility
Institut de Biologie Structurale
CAMPUS EPN
71 avenue des Martyrs
CS 10090
38044 Grenoble Cedex 9
France
0457428554
En savoir plus
https://www.ibs.fr/en/research/assembly-dynamics-and-reactivity/protein-dynamics-and-flexibility-by-nmr-group-m-blackledge/?lang=en
https://scholar.google.com/citations?hl=en&user=m7f8QWQAAAAJ&view_op=list_works&sortby=pubdate