The University of Washington Nanopore Physics Lab investigates two protein porins, mycobacterium smegmatis porin A (MspA) and a -hemolysine porin (aHL) and their interaction with DNA to develop a fast and cheap alternative to current DNA sequencing technologies, as well as to probe nano-scale physics of proteins and polymers.
Our primary aim is to augment nanopore-based sequencing techniques with MspA. DNA sequencing techniques have been around since 1977, and have been continually improved to allow entire genomes comprised of billions of nucleotides to be sequenced. However the developed techniques are still expensive and time-consuming, taking years and millions of dollars to read entire genomes. Improving both the speed and cost of DNA sequencing will have a great impact on the areas of personalized medicine, biotechnology, archaeology, anthropology, genetics, molecular biology, forensic sciences, etc. If nanopore sequencing and is realized, deciphering an entire genome could easily take under a day and only thousands of dollars.
Previously, no biological nanopore other than aHL had been shown to have most of the characteristics needed to sequence DNA. In our recent result (submitted for publication) we reveal MspA is a novel pore that also has some of these necessary characteristics. Though wild-type MspA appears to be unuseable as an assay for DNA, we collaborated with the leading researcher of MspA to genetically engineer MspA into a nucleic-acid (DNA) detector. This accomplishment will open new possibilities within the nanopore-sequencing community. Much exciting work remains to be done.
An alternative goal is to understand the effect of MspA structure on its interaction with the environment. Although a broad aim, understanding how mutations of MspA affect its interaction with lipids and DNA will not only help to guide us in our mutation strategies of MspA, but it will help to provide key insight into the nature of protein.