All of a sudden we will be able to jump from studying behavior one
element at a time to as many as we like at a time. We will be able to
fully recognize everyone on the dance floor. If this does not
accelerate our understanding, it is difficult to imagine what would.
It will of course take time to successfully implement and perfect but
this tells us it is well on the way.
Again it is more good news on the greatest science story ever as we
learn to understand our own biology.
Researchers at
Harvard’s Wyss Institute Engineer Novel DNA Barcode
Researchers have
created a new kind of barcode that uses DNA origami technology.
Colored dots can be arranged into geometric patterns or fluorescent
linear DNA barcodes, and the combinations are almost limitless --
substantially increasing the number of distinct molecules or cells
scientists can observe in a sample. [Credit: Chenxiang Lin, Ralf
Jungmann, Andrew M. Leifer, Chao Li, Daniel Levner, George M. Church,
William M. Shih, Peng Yin, Wyss Institute for Biologically Inspired
Engineering, Harvard Medical School]
New technology could
launch biomedical imaging to next level
BOSTON -- Much like
the checkout clerk uses a machine that scans the barcodes on packages
to identify what customers bought at the store, scientists use
powerful microscopes and their own kinds of barcodes to help them
identify various parts of a cell, or types of molecules at a disease
site. But their barcodes only come in a handful of "styles,"
limiting the number of objects scientists can study in a cell sample
at any one time.
Researchers at the
Wyss Institute for Biologically Inspired Engineering at Harvard
University have created a new kind of barcode that could come in an
almost limitless array of styles -- with the potential to enable
scientists to gather vastly more vital information, at one given
time, than ever before.
The method harnesses
the natural ability of DNA to self-assemble, as reported today in the
online issue of Nature Chemistry.
"We hope this new
method will provide much-needed molecular tools for using
fluorescence microscopy to study complex biological problems,"
says Peng Yin, Wyss core faculty member and study co-author who has
been instrumental in the DNA origami technology at the heart of the
new method.
Fluorescence
microscopy has been a tour de force in biomedical imaging for the
last several decades. In short, scientists couple fluorescent
elements -- the barcodes -- to molecules they know will attach to the
part of the cells they wanted to investigate. Illuminating the sample
triggers each kind of barcode to fluoresce at a particular wavelength
of light, such as red, blue, or green -- indicating where the
molecules of interest are.
Shown here are the
color combinations (216) resulting from attaching just three colors
to a DNA nanotube using origami technology -- underscoring the
potential of this new method. [Credit: Chenxiang Lin, Ralf Jungmann,
Andrew M. Leifer, Chao Li, Daniel Levner, George M. Church, William
M. Shih, Peng Yin, Wyss Institute for Biologically Inspired
Engineering, Harvard Medical School]
However, the method is
limited by the number of colors available -- three or four -- and
sometimes the colors get blurry. That's where the magic of the DNA
barcode comes in: colored-dots can be arranged into geometric
patterns or fluorescent linear barcodes, and the combinations are
almost limitless -- substantially increasing the number of distinct
molecules or cells scientists can observe in a sample, and the colors
are easy to distinguish.
Here's how it works:
DNA origami follows the basic principles of the double helix in which
the molecular bases A (adenosine) only bind to T (thymine), and C
(cytosine) bases only bind to G (guanine). With those "givens"
in place, a long strand of DNA is programmed to self-assemble by
folding in on itself with the help of shorter strands to create
predetermined forms--much like a single sheet of paper is folded to
create a variety of designs in the traditional Japanese art.
To these more
structurally complex DNA nano-structures, researchers can then attach
fluorescent molecules to the desired spots, and use origami
technology to generate a large pool of barcodes out of only a few
fluorescent molecules. That could add a lot to the cellular imaging
"toolbox" because it enables scientists to potentially
light up more cellular structures than ever possible before.
"The intrinsic
rigidity of the engineered DNA nanostructures is this method's
greatest advantage; it holds the fluorescent pattern in place without
the use of external forces. It also holds great promise for using the
method to study cells in their native environments," Yin says.
As proof of concept, the team demonstrated that one of their new
barcodes successfully attached to the surface of a yeast cell.
More research beckons,
particularly to determine what happens when each of the fluorescent
barcodes are mixed together in a cell sample, which is routine in
real-life biological and medical imaging systems--but there's plenty
of good news as a starting point. It's low-cost, easy to do, and more
robust compared to current methods, says Yin.
"We're moving
fast in our ability to manipulate DNA molecules using origami
technology," says Wyss Institute Founding Director Don Ingber,
M.D., Ph.D., "and the landscape of its potential is tremendous
-- from helping us to develop targeted drug-delivery mechanisms to
improving the scope of cellular and molecular activities we are able
to observe at a disease site using the latest medical imaging
techniques."
The research team was
led by three Wyss Founding Core Faculty members: Peng Yin, Ph.D.,
William Shih, Ph.D., and George Church, Ph.D. Yin is also an
Assistant Professor of Systems Biology at Harvard Medical School
(HMS). Church is also Professor of Genetics at HMS and Professor of
Health Sciences and Technology at Harvard and the Massachusetts
Institute of Technology. Shih is an Associate Professor in the
Department of Biological Chemistry and Molecular Pharmacology at HMS
and the Department of Cancer Biology at the Dana-Farber Cancer
Institute. Other research contributors included Chenxiang Lin, Ph.D.,
now Assistant Professor of Cell Biology at Yale School of Medicine;
Wyss Institute Postdoctoral Scholar Ralf Jungmann, Ph.D.; Wyss Staff
Scientist Chao Li, Ph.D.; Wyss Senior Staff Scientist Daniel Levner,
Ph.D.; and Andrew Leifer, Ph.D., formerly at Harvard University, who
is now a Lewis-Sigler Fellow at Princeton University.
The work was funded by
the National Institutes of Health, the National Science Foundation,
the Office of Naval Research, and the Wyss Institute.
For more information,
contact Kristen Kusek
Kristen.kusek@wyss.harvard.edu +1 617-432-8266
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