Scientists from Ecole Polytechnique Fédérale De Lausanne have discovered a way to use a dangerous toxin as a biosensor.
“Pore-forming toxins” (PFTs) are specialised proteins released by certain bacteria. These toxins latch onto the cell’s membrane and form a tube-like channel that goes through it. The hole across the membrane is call a pore. After being punctured by multiple PFTs, the target cell self destructs.
The nano sized pores that they form are used for ‘sensing’ biomolecules (e.g. DNA or RNA) passing through the nanopore like a string steered by a voltage and its individual components give out distinctive electrical signals that can be read out.
Led by Matteo Dal Peraro at Ecole Polytechnique Fédérale De Lausanne, the team of researcher studied a PFT that can be used effectively for more complex sensing, such as protein sequencing. The toxin studied by the team is aerolysin, which is produced by the bacterium Aeromonas hydrophilia, and is the ‘founding member’ of a major family of PFTs found across many organisms.
Aerolysin form very narrow pores that can tell the different between molecules with much higher resolution than other toxins.
The researchers first used a structural model of aerolysin to study its structure using computer simulations. Aerolysin is made up of amino acids, and the model helped the scientists understand how aerolysin’s amino acids affect the function of aerolysin in general.
After studying that relationship, the researchers began to strategically change different amino acids in the computer model. The model then predicted the possible impact of each change on the function of aerolysin.
“By understanding the details of how the structure of the aerolysin pore connects to its function, we can now engineer custom pores for various sensing applications,” says Dal Peraro. “These would open new, unexplored opportunities to sequence biomolecules as DNA, proteins and their post-translational modifications with promising applications in gene sequencing and biomarkers detection for diagnostics.” The scientists have already filed a patent for their sequencing and characterisation of the genetically engineered aerolysin pores.