Descrizione del progetto
Luce, «motore», azione: istantanee di proteine in movimento
Le proteine si trovano ovunque e i loro cambiamenti conformazionali dinamici sono alla base di processi virtualmente illimitati nelle cellule. L’acquisizione di istantanee tridimensionali di questi cambiamenti nel tempo consentirebbe di ottenere informazioni essenziali su processi quali la catalisi enzimatica, la trasduzione del segnale e il ripiegamento delle proteine. Le proteine sono però flessibili e delicate, il che rende difficile lo studio delle loro strutture. Il progetto FemtoPix, finanziato dal CER, prevede di trasformare in realtà l’imaging ultraveloce di singole proteine idratate utilizzando la tecnologia dei laser a elettroni liberi a raggi X. Il team svilupperà una diagnostica per campioni di dimensioni nanometriche, una nuova strumentazione per la consegna dei campioni per consentire l’imaging a diffrazione dei raggi X di singole proteine e un approccio per l’imaging a risoluzione temporale di singole proteine utilizzando la gamma di energia dei raggi X molli. Ciò aprirà la strada alla registrazione di film molecolari.
Obiettivo
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.
Campo scientifico
- natural sciencesphysical sciencesopticsmicroscopy
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein folding
- natural sciencesphysical sciencesopticslaser physicsultrafast lasers
- natural sciencesbiological sciencesbiophysics
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Parole chiave
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-ERC - HORIZON ERC GrantsIstituzione ospitante
751 05 Uppsala
Svezia