NEWS 11/12/2018: Due to a backlog of unpublished manuscripts and
other paperwork, I am unable to consider or process requests for
letters of recommendation, requests for reviews, letters in support of
greencard applications, awards, or any other requests other than those
directly related to current projects in the lab. The sole exception is
for recommendation letter requests for direct student or postdoc
collaborators, or in the case of tenure letters.
NEWS: If you are an undergrad interested in DNA nanotechnology, or
other areas of biomolecular design such as protein design, check out
the BIOMOD biomolecular design
competition run by Shawn Douglas at Harvard.
I am a Research Professor at Caltech where I maintain a small lab
including grad
students, postdocs and visitors. Currently, I collaborate with
postdoc Ashwin Gopinath on the integration of DNA origami into
microfabricated devices, and the applications of this technology to
nanophotonics, nanoelectronics, and biology. With postdoc Cody Geary
and visitor Ebbe Andersen, I work on RNA origami architectures for
folding RNA into arbitrary shapes. We share resources with the laboratory
of professor Erik
Winfree
at Caltech. We collaborate
on many projects; papers are available on the
publications page. My curriculum vitae is available
here.
I have had the good fortune to be supported by the NSF , the CISE directorate Computer & Information
Science and Engineering has been particularly
generous. Similarly, the
Semiconductor Research Corporation , through its FENA program, has funded much of our
recent work attempting to marry DNA self-assembly with
microfabrication. A grant from Microsoft Research seeded
our efforts to study stacking bonds between DNA origami. We have a
grant from the Army (ARO)
Biochemistry program to study the bacterial actin homolog parM
with Dyche Mullins from
UCSF. And we have a grant from DARPA, under its
Living Foundries program, to create excitable biochemical wires
analogous to the long range signal carriers of the nervous system, the
axons.
My interests lie at the interface of computer science,
biology, and chemistry. By this I do not mean the application of
computer science to solve problems in biology or chemistry such as the
protein folding problem. Rather, I am interested in how processes in
biology and chemistry can actually act as computers and execute
molecular algorithms.
In August 2008, a group of 6 Caltech and University of Washington PIs
were awarded a $10 million grant National Science Foundation Grant for
developing this idea: The
Molecular Programming Project . There are several video
presentations linked from this site about Molecular Programming,
including a
public talk which I delivered at the TED conference.
In 2006, I reported a method of creating nanoscale shapes
and patterns using DNA. Each of the two smiley faces above, at right,
are actually giant DNA complexes imaged with an atomic force
microscope. Each is about 100 nanometers across (1/1000th the width of
a human hair), 2 nanometers thick, and each is comprised of about
14,000 DNA bases. 7000 of these DNA bases belong to a long single
strand, a DNA molecule that just happens to be the genome of the virus
M13. The other 7000 of these bases belong to about 250 shorter
strands, each about 30 bases long. These short strands fold the long
strand into the smiley face shape. I call the method "scaffolded DNA
origami". (For the record: there is no fundamental significance to the
fact that it is viral DNA; I could buy it and it was cheap and
pure. M13 is a bacteriophage---it can make the bacteria in your
intestine sick but not you! Also, I apologize to my Japanese
colleagues for the name "DNA origami" which literally translated would
be "DNA paper folding"---English speakers sometimes use "origami" as
verb meaning just "to fold up", similar to the way we use "pretzel" as
a verb---thus "DNA origami" had the feeling of "DNA folding" even
though it is an abuse of the word "origami".)
While the smiley face shape is somewhat silly DNA artwork, it is
a high technology artifact and there is serious science behind it. We
hope to use the technique of DNA origami (as well as many other
techniques of DNA nanotechnology) to build smaller, faster computers
and many other devices.
The best way to understand how this works is to read the
original article published in Nature .
There are two supplemental files associated with this paper. The
first (82 pages, 6.3 megabytes)
describes the design method, block diagrams for the designs,
sequences for all of the designs, and includes data on control
experiments. This file is likely to be of most interest. The second
(9 pages, 192 kilobytes) includes diagrams for all the
designs that have the full sequence written out in the diagrams. This
file is useful if one wishes to check details of the design or modify
them. It cannot be printed clearly and is best viewed with a PDF
viewer on the screen. Please email me with your PDF viewer name and
version if either of these files do not work for you.
I apologize that the MATLAB code for the design of origami structures
has not been released. Unfortunately the code was in such a bad state
that it proved too difficult to clean up for release. Luckily it was
quickly obsolesced by much better software caDNAno , by Shawn Douglas at Harvard.
We use caDNAno to design DNA origami almost every day. It features a
great graphical user interface, and a large number of other scientists
are developing software that interfaces with caDNAno. Thus it has
really become the standard for DNA origami design. The latest version of caDNAno is recommended,
but you may also be interested in a previous version, available from a
repository of legacy caDNAno code
.
If you are interested in DNA origami, and DNA nanotechnology in
general, and want more information, please email me. I maintain a list of
researchers in DNA origami, as well as lists and repositories of references which
I am happy to share.
Once the basic design for a shape has been completed, one can add a
surface pattern on top of the shape. For demonstration purposes in the
Nature paper, the surface pattern was also made out of DNA although in
principle it could be rendered using a chemically, electronically, or
optically interesting material. Because each staple occurs in a
unique location in the origami shape, this location can serve as a
pixel. The normal DNA staple can represent a '0' or a flat pixel. A
modified DNA staple with an extra DNA bump (a DNA hairpin) can be used
to represent a '1'. This is what has been done for the first three
images below, the map, some snowflakes, and the word 'DNA' rendered
above a representation of the double helix. Each of these patterns has
been applied on a roughly 100 nanometer wide rectangle and each pixel
is roughly 6 nanometers in size. Because there are about 200 staples,
each pattern can have 200 pixels. Two copies of the origami have stuck
together in the third image to make the helix appear
continuous. Errors occasionally occur as in the lefthand 'D' in the
first 'DNA' at right.
The structure below is a hexagon that is actually built up of six origami triangles. Each triangle
has a pattern added to it (the green bumps) so that orientation of the triangles in the hexagon can be ascertained.
All of the images shown here are actual atomic force microscope (AFM)
data of DNA molecules (smoothed to remove noise). An AFM measures surface topography. Here,
false color is used to indicate height. The height of a basic shape
(say the smileys) is just the 2 nanometer thickness of DNA. Wherever a
DNA bump has been added in a pattern the surface height is 4
nanometers. The height contrast has been exaggerated (with respect to
the lateral dimensions) to emphasize the topography.
Importantly, there is a long list of people who do work on DNA
nanotechnology. Among them the inventor of DNA
nanotechnology
Ned Seeman at NYU, William Shih at
Harvard, Milan Stojanovic and Darko Stefanovic at Columbia and UNM,
Hao Yan at Arizona State University, Thom LaBean at Duke,
Andrew Turberfield at Oxford,
Hiroshi Sugiyama and Masayuki Endo at Kyoto University,
Bernie Yurke and others in the Nanoscale Materials and Devices Lab
at Boise State University, Hendrik Dietz ,
Fritz Simmel , and
Tim Liedl with their three groups in Munich, and many others.
Also, DNA nanotechnology encompasses much more than just making shapes
as shown above. It includes extended DNA sheets, DNA tubes, DNA
machines, DNA walkers, etc.
email: pwkr@dna.caltech.edu
Rendered by Nick Papadakis, Copyright P.W.K.R. and N.P.