Download Microchip technology rapidly identifies compounds for regrowing nerves, in live animals

Nerve-cell regeneration quest is fast tracked
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Nerve-cell regeneration quest is fast tracked
Microchip technology rapidly identifies compounds for regrowing
nerves, in live animals.
Anne Trafton, MIT News Office
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Lending a hand
October 12, 2010
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Scientists have long sought
the ability to regenerate
nerve cells, or neurons,
which could offer a new way
to treat spinal-cord damage
Astronaut Joseph R. Tanner, STS as well as neurological
-115 mission specialist, waves
diseases such as
toward the digital still camera
during a space walk.
Alzheimer’s or Parkinson’s.
Photo: NASA
Many chemicals can
MIT researchers may be closer regenerate neurons grown in
MIT engineers have developed a way to rapidly perform surgery
to understanding why
on single nerve cells in the worm C. elegans. The white lines
Petri dishes in the lab, but
spacesuit gloves hurt
represent axons — long extensions of nerve cells that carry
it’s difficult and timemessages to other cells.
astronauts’ hands.
Image: Craig Millman and Yanik Lab
consuming to identify those
MIT economist Peter
chemicals that work in live animals, which is critical for developing drugs for humans.
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Engineers at MIT have now used a new microchip technology to rapidly test potential
drugs on tiny worms called C. elegans, which are often used in studies of the nervous
system. Using the new technology, associate professor Mehmet Fatih Yanik and his
colleagues rapidly performed laser surgery, delivered drugs and imaged the resulting
neuron regrowth in thousands of live animals.
“Our technology helps researchers rapidly identify promising chemicals that can then be
tested in mammals and perhaps even in humans,” says Yanik. Using this technique, the
researchers have already identified one promising class of neuronal regenerators.
Mehmet Fatih Yanik
ARCHIVE: "Imaging fish
on the fly"
ARCHIVE: "Live-animal
nerve regeneration study
gets a boost"
tags
biology
computer science and
technology
electrical engineering
and electronics
microfluidics
neuroscience
pharmaceuticals
laser micro-surgery
regeneration
The paper will appear in the online edition of the Proceedings of the National Academy of
Sciences the week of Oct. 11.
Lead authors of the paper are postdoctoral associate Chrysanthi Samara and graduate
students Christopher Rohde and Cody Gilleland, and collaborating chemists are Steve
Haggarty and Stephanie Norton. Development of the new technology and the
regeneration screen was funded by the NIH Director’s New Innovator Award Program, a
Packard Fellowship in Science and Engineering, an Alfred Sloan Award in Neuroscience,
an NSF Graduate Fellowship and a Merck Graduate Fellowship.
Rapid analysis
C. elegans is a useful model organism for neuron regeneration because it is optically
transparent, and its entire neural network is known. Yanik and colleagues had previously
developed a femtosecond laser nanosurgery technique which allowed them to cut and
observe regeneration of individual axons — long extensions of neurons that send signals
to neighboring cells. Their femtosecond laser nanosurgery technique uses tightly-focused
infrared laser pulses that are shorter than billionth of a second. This allows the laser to
penetrate deep into the animals without damaging the tissues on its way, until the laser
beam hits its final target.
In the PNAS study, the researchers used their microchip technology to rapidly cut the
axons of single neurons that sense touch. Moving single worms from their incubation well
http://web.mit.edu/newsoffice/2010/neural-regeneration-1012.html
10/13/2010
Nerve-cell regeneration quest is fast tracked
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to an imaging microchip, immobilizing them and performing laser surgery takes only about
20 seconds, which allows thousands of surgeries to be performed in a short period of
time.
After laser surgery, each worm is returned to its incubation well and treated with a different
chemical compound. C. elegans neurons can partially regrow without help, which allowed
Yanik’s team to look for drugs that can either enhance or inhibit this regrowth. After two or
three days, the researchers imaged each worm to see if the drugs had any effect.
The MIT team found that a compound called staurosporine, which inhibits certain
enzymes known as PKC kinases, had the strongest inhibitory effect. In a follow-up study,
they tested some compounds that activate these kinases, and found that one of them
stimulated regeneration of neurons significantly. Some of Yanik’s students are now testing
those compounds on neurons derived from human embryonic stem cells.
The new technology represents a significant advance in the level of automation that can
be achieved in C. elegans studies, says Michael Bastiani, professor of biology at the
University of Utah. “Using ‘classical’ handling techniques you can cut and assay at most
100 animals per day,” he says. “Yanik's automated system seems like it could increase
throughput by at least 10-fold over that number.” He points out that one potential limitation
of the system is that it might not pick up the effects of neural regenerators that can’t
penetrate the worm’s cuticle, a thick outer layer that surrounds the skin.
However, chemicals can still be taken up through the worms’ digestive tract, which is an
important test for checking whether chemicals would work on live animals, says Yanik.
This microchip technology can also be used to screen compounds for their effects on
other diseases such as Alzheimer’s, Parkinson’s and ALS, says Yanik.
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http://web.mit.edu/newsoffice/2010/neural-regeneration-1012.html
10/13/2010