Nanopore Design and Engineering
Where Chemistry, Biology and Nanotechnology meet up
One of the main focus in our laboratory is to design and re-engineer membrane proteins and nanopores to modify their properties.
We use a range of techniques including directed evolution, genetic engineering, bioorthogonal chemical modifications (e.g. by covalently attaching DNA molecules) and computational approaches (with Prof. S. Marrink) to introduce target functions to the nanopore.
Nanopore design and engineering
Virtually all cells make proteins that form nanoscale holes on biological membranes, thus hundreds of biological nanopores are available. However, today only a few nanopores with different size, shape and properties are available. One important line of research in our laboratory is to characterise nanopores which structure is available (Figure below). Another is the de novo design nanopores with tailored properties.
Origin of Membrane Proteins
Arguably, one of the first events of cellular life was the formation of a permeable protective barrier that allowed the communication between the cell and the environment. We are aiming to recreate the spark that ignited cellular life by designing, engineering and evolving molecular components that specifically control cellular communication.
Bottom-up fabrication of a proteasome–nanopore that unravels and processes single proteins Nature Chemistry (2021).https://doi.org/10.1038/s41557-021-00824-w
The Manipulation of the Internal Hydrophobicity of FraC Nanopores Augments Peptide Capture and Recognition. ACS Nano (2021).https://doi.org/10.1021/acsnano.0c09958
Accurate modeling of a biological nanopore with an extended continuum framework. Nanoscale (2020) 10.1039/D0NR03114C
Electro-osmotic vortices promote the capture of folded proteins by PlyAB nanopores. Nano Letters (2020). https://doi.org/10.1021/acs.nanolett.0c00877
Reversible photo-controlled nanopore assembly. JACS (2019) doi.org/10.1021/jacs.9b06998
DNA capture into the ClyA nanopore: diffusion-limited versus reaction-limited processes. J Phys Condens Matter (2018) 10.1088/1361-648X/aacc01
Alpha-helical Fragaceatoxin C nanopore engineered for double stranded and single stranded nucleic acid analysis. Angewandte Chemie 10.1002/anie.201606742.
Engineering a nanopore with co-chaperonin function. Science Advances. (2015) 10.1126/sciadv.1500905.