NPCCRYOET

A combined approach of cryo-electron tomography and protein tagging for elucidating the structural organization of the human Nuclear Pore Complex

Coordinatore	EUROPEAN MOLECULAR BIOLOGY LABORATORY    more  Organization address address: Meyerhofstrasse 1 city: HEIDELBERG postcode: 69117 contact info Titolo: Ms. Nome: Jillian Cognome: Rowe Email: send email Telefono: +49 6221 387 8316 Fax: +49 6221 387 8301
Nazionalità Coordinatore	Germany [DE]
Totale costo	174˙475 €
EC contributo	174˙475 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2011-IEF
Funding Scheme	MC-IEF
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-12-01   -   2014-11-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	EUROPEAN MOLECULAR BIOLOGY LABORATORY  Organization address address: Meyerhofstrasse 1 city: HEIDELBERG postcode: 69117 contact info Titolo: Ms. Nome: Jillian Cognome: Rowe Email: send email Telefono: +49 6221 387 8316 Fax: +49 6221 387 8301	DE (HEIDELBERG)	coordinator	174˙475.20

Mappa

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 Obiettivo del progetto (Objective)

'Nuclear Pore Complexes (NPCs) represent the exclusive passageway in and out of the nucleus but also function in gene regulation and nuclear organization. NPCs serve as docking sites for many viruses and were associated with several human diseases, e.g. leukemia. Understanding the nuclear transport mechanism will have a huge impact on human health research of such diseases. Multiple copies of ~30 different protein components, termed nucleoporins (Nups), form the major building blocks of NPC. Nups are organized as repetitive modules, called subcomplexes. The subcomplexes, in turn, form the scaffold of NPC in an unknown arrangement. Despite their importance, structure determination of NPCs is a considerable challenge, primarily due to their sheer size.

To generate an atomic model of the human NPC, data at the different resolution levels have to be systematically collected and integrated. Determining the position of Nup subcomplexes within the NPC will be a critical step to bridge the resolution gap between different structural techniques. Since the precision of 2D-immuno-gold labeling techniques is insufficient to associate individual Nups with distinct features of the NPC structure from cryo-electron tomography (cryo-ET), alternative strategies are needed to achieve this goal. Here I propose to improve the resolution of the human NPC structure to allow assigning subcomplexes into the overall assembly. This will be achieved by cryo-ET, subtomogram averaging and further development of algorithms correcting for NPC plasticity. Furthermore, I will determine the precise positioning of subcomplexes by obtaining 3D structures of NPCs containing tagged Nups. This will contribute significantly to our understanding of the overall organization of the NPC and thus, nuclear tranport mechanism. This proposed project will give me the opportunity to learn new skills, acquire competencies and, thus pave the way towards an independent career.'

Introduzione (Teaser)

Nuclear pore complexes (NPCs) in the nuclear envelope surrounding the nucleus regulate much more than bi-directional transport. Pioneering work has revealed subcomplex structural information for the first time, opening the door to elucidation of function.