Nuclear pore complexes (NPCs) are large multi-protein structures (~125 MDa) spanning the double membrane of the nucleus and acting as the only gateway of nucleocytoplasmic transport. The three dimensional (3D) architecture of the NPC, its role in trafficking of proteins and RNA, and its molecular composition (nucleoporins 'Nups') have been extensively studied.
Nonetheless, to understand how the NPC mediates nucleocytoplasmic exchange requires the independent characterization of its molecular components at atomic resolution and a detailed description of physical interactions between nucleoporins in the NPC assembly. Crystal structures of three nucleoporin domains have been resolved (Nup98, hNup133, Nup159), although no atomic model for any sub-complex of N ups is yet available.
This proposal aims to elucidate the structure of the nuclear pore subcomplex p62, a biomedical agent essential to signal-mediated nucleocytoplasmic transport, using 'bi-cistronic multiple co-expression' for in vitro complex reconstitution and X-ray crystallography. This accomplishment will contribute to the construction of parts of the NPC at atomic detail essential to understand nucleocytoplasmic trafficking and to establish basic knowledge into human diseases caused by disruption of transport pathways (objective of the LifeSciHealth Priority Programme of Framework 6).
The applicant, of Spanish nationality, will accomplish this task under the supervision of Dr. Olga Mayans at the renowned Swiss institute Biozentrum (in compliance with the section 220.127.116.11 of the WP HRM). The multidisciplinary and advanced training received by the applicant will complement and expand her technical experience and research management capabilities to initiate an independent career in Molecular Structural Biology.
Fields of science
- engineering and technologymaterials engineeringcrystals
- natural sciencesearth and related environmental sciencesgeologymineralogycrystallography
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesgeneticsRNA
- natural sciencesbiological sciencesmolecular biologystructural biology
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