Sequencing 'ALIEN' DNA and watching molecular motors at work: DNA is an incredibly dense information storage system used by all life as we know it. Genetic information is encoded in the sequence of bases A, C, G, & T. Sequencing DNA is a remarkable feat of engineering. Individual DNA bases differ from one another by just a few atoms and occur in a chain separated from each other by just ~6 Ångstroms, while typical genomes are billions of bases long. A decade ago, our group was the first to demonstrate a new way of sequencing DNA using a nanopore that is now regularly used by geneticists world-wide. In my talk, I’ll describe how nanopore sequencing works and how we’re working to improve it and expand its use beyond ACGT-DNA. Notably, it is the first sequencing technology based on a physical measurement of DNA bases. We took advantage of this to enable the first sequencing of “ALternative Isoinformational ENgineered” (ALIEN) DNA, a biomimetic genetic polymer. ALIEN DNA has the same sugar-phosphate backbone as natural DNA, however its bases “P," "Z," "S," & "B,” are entirely anthropogenic and base-pair orthogonally to ACGT DNA. In the second half of my talk I’ll show how the nanopore can be used as a powerful new single-molecule tool to observe the biophysics of molecular motors at unrivaled spatiotemporal resolution, revealing how they use chemical energy to perform work and walk along DNA.