We are biological physicists pursuing single molecule measurements involving a nanopore. In particular we are working on a method to sequence DNA. Such DNA sequencing would be particularly fast and cheap.

The concept of nanopore sequencing is simple: Electrophoretically drive DNA through a tiny pore, and use that pore to read out the DNA. A number of schemes have been proposed, but conceptually the simplest is to measure the simultaneously passing ionic current through the pore. The traversing DNA modulates the ion current and provides direct information about the structure of the DNA. Ideally (and naively) one would detect a distinct current level for each nucleotide passing through the pore. The field of nanopore sequencing was founded using the well studied pore &alpha-Hemolysin. For a few years we have also used the work horse &alpha-Hemolysin , but we have recently introduced a new biological pore to the playing field: Mycobacterium smegmatis porin A (MspA). This naturally occuring rugged pore has an ideal shape for the task. Together with micro biologists at the University of Alabama at Birmingham, who dicovered MspA in tuberculosis related research, we are now modifying this pore protein to optimize it for sequencing. Through molecular dynamics simulation carried out by collaborating physicists at the University of Illinois, Urbana-Champaign we are learning more about the nano-scale dynamics of single-stranded DNA in MspA, leading us to rational design of MspA at the sub-nanometer scale.