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Helico-Selective Membrane Transport

Project description

Engineered nanopores control transport via helical tags

Membranes are characteristic features of eukaryotic cells, serving to compartmentalise and control essential functions and materials. Transmembrane transport of molecules is regulated very precisely via specialised pore-forming membrane proteins. Replicating this machinery remains a challenge. The ERC-funded ChiroPore project aims to address this with inspiration from nuclear pore complexes and helical peptides, structures crucial to biological functions and heavily researched in drug design. Nanoscale pores will be engineered from a variety of transmembrane peptide barrels and helical peptides using advanced ‘origami’. The pores will selectively recognise and admit only molecules carrying a matching helical tag. Success could open transformative new possibilities in targeted drug or gene delivery, biosensing, signalling and precise manipulation of cellular communication.

Objective

Membrane transport regulation is a sophisticated process only achieved by complex pore-forming membrane proteins. Controlling the transportation of bioactive molecules with high selectivity can pioneer a paradigm shift in the precision of membrane-related applications (e.g. drug and gene delivery, biosensing, signaling, metabolic activity manipulation, etc.).

Despite the research effort in membrane transport and significant advances in membrane pore engineering, a critical knowledge gap still hinders the development of pore technologies for high-selective membrane translocation processes. Inspired by the recognition mechanisms of transport-specialized membrane proteins, ChiroPore aims to fill this gap by using helical topologies as recognition patterns in nanopore-mediated membrane translocation for the first time.

Inspired by natural tagging recognition systems like nuclear nanopores, ChiroPore’s strategy consists of a two-component system in which matching helical topologies are used as recognition motifs, akin to bolt and nut complementarity. A variety of nuts (transmembrane peptide barrels) and bolts (helical peptides) designed with helical complementarities form the basis of a versatile multivalent key-lock system for tag-selective membrane trespassing of bioactive cargo.

I will synergistically combine the advantages of existing membrane nanopore engineering strategies into a novel peptide assembly technology to construct membrane pores with precise internal topology. I propose introducing a helical peptide nucleic acid (α-PNA) origami to synthesize membrane-spanning barrels capable of displaying an array of helical topologies.

Overall, ChiroPore technology proposes a tag-selective supramolecular membrane transport system that utilizes macromolecular chirality as a recognition motif. This system will contribute to progress toward high-precision delivery, sensing, and communication applications at the cellular level.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2025-COG

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Host institution

UNIVERSIDAD DE SANTIAGO DE COMPOSTELA
Net EU contribution
€ 1 999 625,00
Address
COLEXIO DE SAN XEROME PRAZA DO OBRADOIRO S/N
15782 Santiago De Compostela
Spain
Region
Noroeste Galicia A Coruña
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 1 999 625,00

Beneficiaries (1)