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Selective transport control in biological and biomimetic nanopores

General Information

The conference will take place from June 24-28, 2024 at the Congressi Stefano Franscini (CSF) in Monte Verità, which is perched above Lago Maggiore in the city of Ascona, Canton Ticino in the south of Switzerland.

Event description

Nuclear pore complexes (NPCs) are remarkable sorting machines that mediate nucleocytoplasmic transport (NCT). NCT is a highly regulated process that underlies the trafficking of essential macromolecular cargoes between the cytoplasm and nucleus in eukaryotic cells. These range from the import of transcription factors into the nucleus to the export of messenger ribonucleoproteins (mRNPs) out of it. Transport through the NPC is highly selective and the unsolicited passage of non-specific cargoes is suppressed. To underscore its importance, defective NPC/NCT function is associated with neurodegeneration, aging, and viral infections.

When considered in physical terms, NPC function is compelling because macromolecular transport is restricted or promoted via biochemical selectivity and not by size selection per se. The biochemical selectivity derives from the behavior of intrinsically disordered proteins termed phenylalanine-glycine nucleoporins (FG Nups) that generate a permeability barrier within its 60 nm-diameter central channel. NCT selectivity is facilitated by cargo-carrying nuclear transport receptors termed karyopherins (Kaps), which exert multivalent interactions with the FG Nups to rapidly diffuse through the NPC. However, the number of NPCs in the cell is exceedingly small compared to the number of Kaps, so that in fact there is a high likelihood that the pores are always populated by Kaps. This raises the following key questions: (1) What is the fundamental nature of the NPC permeability barrier? (2) How do Kaps rapidly move through the NPC permeability barrier? (3) How do over-sized cargoes (e.g. viral capsids) overcome the NPC permeability barrier?

These are multifaceted problems that require an interdisciplinary effort to address. Indeed, recent breakthroughs have benefited from advances in theoretical, computational and experimental methods. Another exciting development pertains to the design of biomimetic ‘NPCs’ that have been shown to reconstitute aspects of NPC function by incorporating FG Nups or other bio-functional “smart” polymers into DNA origami-based and other synthetic nanopores. In this way, such NPC biomimics may be used in emergent technologies such as DNA sequencing, water purification and biological sensing. Taken together, this epitomizes the close synergies between NPC function, smart polymers and synthetic nanopores.

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