University of Groningen Associate Professor in Chemical Biology Giovanni Maglia has received an ERC Consolidator Grant for his project on the design of new nanopores. He wants to use these pores to identify proteins, which may result in new diagnostic devices. The EUR 2 million grant follows an earlier ERC Starting Grant for Maglia.
Nanopores are a class of membrane proteins that form nanoscale holes in biological membranes. In nature nanopores allow different nutrients to cross cell membranes. Modified pores in artificial membranes are currently in use to sequence DNA. ‘These pores allow an ionic current to pass across the membrane, and any substance entering the pore will interfere with this current’, Maglia explains. ‘The four bases in DNA affect the current in different ways, so when a DNA molecule passes through the pore, it is possible to read the order of the bases.’ Portable devices which use this technique are already commercially available.
In his previous work, Maglia used nanopores to study single molecules. Again, the molecule inside the pore affects the current across the membrane, and changes in the molecule cause a measurable change in the ionic current. In all these cases, modified natural pores are used. But this time, Maglia wants to design new pores from scratch.
‘We will first study how pore proteins enter membranes. Then, we’ll use molecular dynamics to simulate the way new pore proteins behave inside the membrane.’ Finally, he will pair nanoscale machines to control the passage of proteins across the nanopore. Designing entirely new pore proteins, especially with complex new functions, is something no one has done so far, but as a leading expert in nanopore engineering, Maglia is confident he will be able to do so during the five-year project.
His aim is to construct a pore that will recognize proteins passing through it. ‘Then, using the kind of devices that are already constructed to study DNA with nanopores, it will be possible to recognize specific proteins in biological samples.’ Such a device could be used for medical diagnostics.
For Maglia, the most important aspect is to prove it is possible to design pores from scratch. ‘Nanopores can be used for different practical applications and for research purposes, but so far we are limited by the type of pores that Nature provides. Finding a way to design them will remove this limitation.’
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