Single Molecule Science Special Seminar

Speaker: Professor William Shih, Harvard Medical School, Dana-Farber Cancer Institute and the Wyss Institute

William Shih is a Professor in the Department of Biological Chemistry and Molecular Pharmacology at
Harvard Medical School and the Department of Cancer Biology at the Dana-Farber Cancer Institute and a
Core Faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard. William
studied Biochemical Sciences at Harvard for his A.B. (1990–1994) and Biochemistry at Stanford for his
Ph.D. (1994–2000) He did a postdoctoral fellowship at The Scripps Research Institute (2001–2004) and
has since been back at Harvard as a faculty member. William was a 2008 NIH Director’s New Innovator
Awardee, a 2013 Blavatnik National Award Finalist in the Physical Sciences, the 2017 Foresight Prize
Awardee in Experimental Nanotechnology, and the 2018 Rozenberg Tulip Awardee in DNA Computing.

DNA Origami Barrels
DNA origami, in which a long scaffold strand is assembled with a large number of short staple strands into
parallel arrays of double helices, has proven a powerful method for custom nanofabrication. Although
diverse shapes in 2D are possible, the single-layer rectangle has proven the most popular, as it features
fast and robust folding and modular design of staple strands for simple abstraction to a regular pixel
surface. Here we introduce a barrel architecture, built as stacked rings of double helices, that retains these
appealing features, while extending construction into 3D. We demonstrate hierarchical assembly of a 100
megadalton barrel that is ~90 nm in diameter and ~270 nm in height, and that provides a rhombic-lattice
canvas of a thousand pixels each, with a pitch of 9 nm, on its inner and outer surfaces. Complex patterns
rendered on these surfaces were resolved using up to twelve rounds of exchange PAINT super-resolution
fluorescence microscopy. We envision these structures as versatile nanoscale pegboards for applications
requiring complex 3D arrangements of matter. One application I will discuss is the use of DNA barrels to
scaffold the manufacture large lipid nanodiscs suitable for cryoEM structure determination of large
membrane proteins and their complexes embedded in a native lipid bilayer environment.