Objective This proposal aims at developing novel hybrid DNA-protein nanopores with well-defined, uniform channel sizes, to advance fundamental studies on transport across membranes and to enable the development of new biosensors and progress towards creating artificial cells and tissues. Currently used protein nanopores either have a limited cargo capacity, which is set by their internal diameter, or they are heterogeneous in size and sometimes incompletely assembled. I propose to use DNA origami nanostructures as scaffolds for barrel- and ring-forming peptides of alpha-haemolysin and ClyA/Wza to create hybrid pores with larger and uniform pore sizes. These hybrid pores have the advantage that they are fully biocompatible and retain the potential for genetic and chemical engineering at the level of the DNA and proteins through the use of nucleotide recognition sequences and functionalised amino acid residues. By systematic characterisation of the hybrid nanopores in the controlled environment of droplet interface bilayers using single-channel current recordings and fluorescent detection of transport across membranes, the proposed hybrid nanopores will provide valuable insights into membrane transport and potential applications in biotechnology and medicine. Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural sciencesbiological sciencesgeneticsnucleotidesnatural scienceschemical sciencesorganic chemistryaminesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Keywords nanopores alpha-haemolysin protein engineering DNA-origami membrane transport biosensors Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2014 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Net EU contribution € 195 454,80 Address WELLINGTON SQUARE UNIVERSITY OFFICES OX1 2JD Oxford United Kingdom See on map Region South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 195 454,80