Descrizione del progetto
Uno zoom sulle strutture proteiche potrebbe espandere significativamente le opportunità di trattamento per le disfunzioni
Le proteine, comprendenti anticorpi, enzimi e ormoni, sono molecole grandi e complesse necessarie per la maggior parte delle funzioni cellulari. Non sorprende che una disfunzione proteica sia alla radice di numerose malattie e condizioni. Un meccanismo caratteristico dell’attività proteica consiste nel legarsi ad altre molecole a livello di siti specifici attraverso cambiamenti conformazionali. La caratterizzazione precisa della struttura 3D dettagliata alla base di funzioni specifiche è fondamentale per far progredire la comprensione. La microscopia crioelettronica, vincitrice del Nobel, consente l’imaging di campioni idratati congelati nel loro stato nativo senza coloranti o fissativi, aprendo una nuova finestra su fini strutture cellulari a risoluzione molecolare. IMpaCT sta utilizzando questa tecnica rivoluzionaria per visualizzare le proteine legate alla salute umana aumentando al contempo la visibilità dell’università coordinatrice.
Obiettivo
Proteins are building blocks of life, often forming complexes with essential cellular roles. Dysfunction of proteins or their complexes in cells are associated with a wide variety of pathologies, making them excellent drug target candidates. Their 3D structures are essential for a rational drug design. However, many important proteins and complexes are extremely hard to crystallize. Recent advances in Cryo-Electron Microscopy methodologies enabled the structure determination of large macromolecular complexes at near-atomic resolution. An unprecedented level of detail in cell imaging using Cryo-Electron Tomography is also now possible. IMpaCT will improve the expertise at the UNL in Cryo-EM methodologies applied to the structural studies of proteins related to human health (e.g. cancer, antiviral infections) from individual molecules to macromolecular complexes, both isolated and in a cellular context. To this end, UNL will team up with renowned Cryo-EM experts from the National Centre for Biotechnology of the Spanish National Research Council (Spain), the Institute of Biotechnology of the University of Helsinki (Finland) and the Weizmann Institute of Science (Israel). A solid work programme grounded on hands-on Workshops will be complemented with short-term visits to the partner labs, visits from partner labs experts to ITQB NOVA, seminars by leading experts in Cryo-EM (e.g. Nobel Prize winners), industry stakeholders’ engagement via a Mini-symposium and workshop participation, knowledge transfer to other research groups in Portugal and a WP devoted to early-stage researchers. An ambitious Dissemination, Exploitation and Communication plan will be implemented to leverage the research results potentiated by this project as high-impact publications and invited communications at international meetings, leading to a fundamental outcome: an increased visibility and activity of UNL researchers as players in the Cryo-EM field.
Campo scientifico
Parole chiave
Programma(i)
- H2020-EU.4.b. - Twinning of research institutions Main Programme
Argomento(i)
Invito a presentare proposte
Vedi altri progetti per questo bandoBando secondario
H2020-WIDESPREAD-2018-03
Meccanismo di finanziamento
CSA - Coordination and support actionCoordinatore
1099 085 Lisboa
Portogallo