Description du projet
Lumière, caméra, action: instantanés de protéines en mouvement
Les protéines sont omniprésentes et leurs changements de conformation dynamiques sous-tendent un nombre pratiquement illimité de processus cellulaires. La prise d’instantanés en 3D de ces changements au fil pourrait apporter des informations essentielles relatives à des processus tels que la catalyse enzymatique, la transduction de signal et le repliement des protéines. Les protéines sont toutefois flexibles et délicates, ce qui complexifie l’étude de leur structure. Le projet FemtoPix, financé par le CER, entend faire de l’imagerie ultrarapide de protéines uniques hydratées une réalité grâce à la technologie des lasers à rayons X à électrons libres. L’équipe développera des diagnostics pour les échantillons de taille nanométrique, de nouveaux instruments de distribution d’échantillons pour permettre l’imagerie par diffraction des rayon X d’une seule protéine, et une approche pour l’imagerie d’une seule protéine résolue dans le temps en utilisant la gamme d’énergie des rayons X tendres. Cela ouvrira la voie à l’enregistrement de films moléculaires.
Objectif
Conformational dynamics are crucial for the functioning of most macromolecules and a deeper understanding of these motions holds great promise for future discoveries in biology. But it is difficult to probe the structure of macromolecules away from their most stable conformations, and time-resolved studies remain limited by the available techniques.
Today a new generation of XFELs is growing. The extremely short pulse duration, high pulse intensity and repetition rate of these lasers offer new research opportunities in physics, chemistry, and biology.
Since the first XFELs were proposed, the idea of obtaining images of individual proteins frozen in time has fascinated and inspired many, and we have been at the forefront of this quest. The combination of advances in XFEL technology with ESI has brought the dream of imaging hydrated single proteins by X-ray diffraction within reach.
Currently time-resolved studies in solution in the sub-ms range are done through solution X-ray scattering or spectroscopic methods, but they can only provide limited structural information. XFELs provide a way to dramatically improve our understanding of these time-scales. This proposal aims to develop the science and technology to make ultrafast single-protein imaging a reality, through a three-step approach: (I) develop diagnostics suitable for nanosized samples, (II) enable single protein X-ray diffraction imaging through new sample delivery instrumentation, (III) perform time-resolved single protein imaging experiments using the unexplored tender X-ray energy range.
Ultrafast imaging of macromolecules will reveal new horizons. As a single-molecule method with high time-resolution, it enables imaging the structural changes associated with fundamental processes such as enzyme catalysis, allosteric signal transduction or even protein folding. It also opens a way to record molecular movies and mapping the conformational landscape of isolated macromolecules for the first time.
Champ scientifique
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein folding
- natural sciencesphysical sciencesopticslaser physicsultrafast lasers
- natural sciencesbiological sciencesbiophysics
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
751 05 Uppsala
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