HDR de Slavica Jonic - Jeudi 26 novembre 2015 à 14 h

Université P. et M. Curie, 4, Place Jussieu, 75005 Paris

Amphi Astier - Bâtiment Esclangon

"Structure and dynamics by electron microscopy and X-ray free electron lasers: Data analysis algorithms and computational tools for structural biology applications"

Abstract

Biological molecular complexes such as proteins and RNAs are of great interest in the area of molecular biology as they are involved in core biological functions such as gene transcription, protein synthesis, and cellular transport. Such systems undergo large conformational transitions to achieve functions. Therefore, characterization of structure and dynamics of these macromolecular complexes is crucial to understand their functional mechanisms, and plays an important role in the development of new drugs to treat human diseases. X-ray crystallography has been the primary tool to study protein conformations, providing high-resolution structures. However, crystallization is difficult in the case of large complexes with conformational flexibility. We have recently shown that single-particle EM can be used to study full and continuous conformational dynamics (a full set of intermediate states of a gradual conformational change) in cryo conditions (close to physiological conditions). Following the example of EM, single-particle X-ray free-electron laser (XFEL) experiments are currently under development because of their great potential to fully investigate dynamics of biological systems under physiological conditions, such as in cellular environment. Current major approach to study biomolecular structures by XFEL is serial femtosecond crystallography that allows structural resolution at atomic level but requires crystallization and cannot be used to study full dynamics. Thus, single-particle XFEL (without crystallization) is currently under development to allow studying full conformational dynamics in physiological conditions. Because of the impact that current EM and XFEL technological developments may have in a near future, it is important to work on the development of single-particle EM image analysis approaches for studying structure and dynamics of macromolecular complexes and on their extensions to single-particle XFEL experiments.


Jury

- M. Guy SCHOEHN (DR CNRS, IBS Grenoble), reviewer
- M. Charles KERVRANN (DR INRIA, INRIA Rennes - Bretagne Atlantique), reviewer
- Mme Elena ORLOVA (Prof. Birkbeck College, United Kingdom), reviewer
- M. Pascal FREY (Prof. UPMC, ICS UPMC)
- M. Sergio MARCO (DR INSERM, Institut Curie Orsay)
- Mme Aleksandra KORAC (Prof. University of Belgrade, Serbia)