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SUMMARY:Deconstructing Nuclear Pore Complex Function by Bio-Synthetic Reco
 nstruction - Professor Roderick Lim\,  University of Basel\, Switzerland
DTSTART:20120119T140000Z
DTEND:20120119T150000Z
UID:TALK35696@talks.cam.ac.uk
CONTACT:Tracy Inman
DESCRIPTION:The manner by which specific macromolecules are sorted and tra
 nsported in the complex environment of living cells (i.e.\, protein target
 ing) is unprecedented and unmatched by technology. Yet\, how does a molecu
 le get to exactly where it is supposed to in the cell? This defines the dr
 iving impetus in our lab to resolve the modus operandi of the nuclear pore
  complex (NPC)\, which regulates macromolecular traffic between the nucleu
 s and the cytoplasm. \n\nAs a 50 nm-diameter physical pore\, the biolog
 ical marvel of the NPC lies in its ability to restrict or promote cargo tr
 anslocation via biochemical selectivity and not size exclusion per se. Mor
 eover\, unlike synthetic nanopores\, the NPC does not clog in vivo - in sp
 ite of the molecular complexity of the cellular environment. \n\nHere we u
 se a hybrid methods approach to resolve and correlate across the pertinent
  biophysical\, biochemical and structural aspects of NPC functionality. Th
 ese efforts range from (i) applying AFM to study the nanomechanical respon
 se of the key NPC proteins (i.e.\, intrinsically disordered phenylalanine-
 glycine (FG)-rich nucleoporins or FG Nups) on pore-like nanostructures\; (
 ii) to correlating binding-induced conformational changes in the FG Nups t
 o binding affinities using surface plasmon resonance\; (iii) to constructi
 ng biomimetic nanopores that reproduce the transport selectivity of the NP
 C. \n\nIn my talk\, I will describe how these efforts provide new insight 
 into the underlying principles governing molecular mechanics\, selectivity
  and transport in the NPC. By replacing the NPC machinery with synthetic p
 olymers\, I will further demonstrate how NPC-like functionality can be har
 nessed to target specific proteins from authentic biological environments 
 to site-selective locations with nanoscale precision in technological syst
 ems.\n\n\n\n1.	J. T. Hyotyla\, J. Deng and R. Y. H. Lim\, Synthetic Protei
 n Targeting by the Intrinsic Biorecognition Functionality of Poly(ethylene
  glycol) using PEG-Antibodies as Biohybrid Molecular Adaptors\, ACS Nano\,
  5 5180 (2011)\n2.	S. W. Kowalczyk\, L. Kapinos\, T. Magalhães\, P. van N
 ies\, R. Y. H. Lim*\, and C. Dekker*\, Single-Molecule Transport Across an
  Individual Biomimetic Nuclear Pore Complex\, Nature Nanotechnology\, 6 43
 3 (2011)\n3.	Peleg O. and Lim R. Y. H.\, Converging on the Function of Int
 rinsically Disordered Nucleoporins in the Nuclear Pore Complex\, Biologica
 l Chemistry 391 719 (2010)\n4.	R. Y. H. Lim\, B. Fahrenkrog\, J. Koser\, K
 . Schwarz-Herion\, J. Deng\, and U. Aebi\, Nanomechanical Basis of Selecti
 ve Gating by the Nuclear Pore Complex\, Science\, 318 640 (2007)  \n5.	Lim
 \, R. Y. H.\, Huang\, N. P.\, Koser\, J.\, Deng\, J.\, Lau\, K. H. A.\, Sc
 hwarz-Herion\, K.\, Fahrenkrog\, B. & Aebi\, U. Flexible Phenylalanine-Gly
 cine Nucleoporins as Entropic Barriers to Nucleocytoplasmic Transport\, PN
 AS 103\, 9512 (2006)\n
LOCATION:Pippard Lecture Theatre\, Cavendish Laboratory
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