Maverick Science mag 2013-14

things would not be possible
without him.”
Another of Mohanty’s current
projects, which the twophoton
optogenetic stimulator
builds upon, involves finding a
better way to initiate certain
gene therapies that are more
effective against retinitis pigmentosa,
an inherited eye disease
that causes progressive
vision loss and can cause blindness.
Mohanty will receive
$384,269 over the next two
years from the National Institutes
of Health for the project.
The study involves using NIR
ultrafast laser beams to deliver
genes that allow expression of
light-sensitive proteins, called
opsins, in specific cells. The
proteins’ expression allows researchers
to influence neural
activity through optogenetics.
In the past, the genes have
been delivered to cells by a
virus, but that method has
drawbacks, such as undesired
immune responses, in addition
to the benefits. In Mohanty’s
method, a laser beam creates a
“It is becoming evident that physics and
new physical tools and materials are playing
very important – almost inevitable – roles
in answering key questions in biology and
medicine.”
– Samarendra Mohanty
transient sub-micrometersized
hole, which allows for the
gene encoding the proteins to
permeate the cell membrane. It
can limit the risk of immune
response as well as deliver
larger genes than viral methods, he said.
“Our minimally invasive near-infrared method can deliver DNA and other
impermeable molecules effectively where you want it and only where you want
it,” Mohanty said. “For example, in retinitis pigmentosa, only the peripheral
retina begins to lose light sensitivity due to loss of photoreceptors. This is
where a laser can deliver the genes, making those neurons respond to light
again. With a virus, the genes will be delivered everywhere, causing complications
in areas already working fine.”
Optogenetic stimulation also holds promise for influencing neurons in the
brain. Scientists, including Mohanty’s lab group, are studying ways it could
be used to understand how the brain works or to intervene in cases of neurological
disorders or to affect behavior. Ultimately, Mohanty’s team has a goal
of creating all-optical, or light-based, control and monitoring of cell activity.
So, in addition to the light-assisted delivery of genes, his lab also will work on
refining methods for stimulating the neural activity using NIR and visible
light.
“Dr. Mohanty's innovations continue to be recognized because of the great
potential they hold," College of Science Dean Pamela Jansma said. "Hopefully,
his work will one day provide researchers in other fields the tools they need
to examine how the human body works and why normal processes sometimes
fail.”
A
nother major focus of Mohanty’s research is to understand
the mysterious ways by which different
types of neurons – nerve cells that are the basic
building block of the nervous system – and neuronal
circuits respond to physical cues such as force, flow
and heat. Information is transmitted between neurons
via axons, or nerve fibers, which are long, slender
appendages. The process of sending messages
from one neuron to another depends on connection
between neurons, which requires axonal guidance. Although numerous methods
to achieve fully-controlled
axonal guidance have been introduced,
they are ineffective or
require introducing invasive
external factors, Mohanty said.
“Recently, we discovered
that an important physical cue,
heat, can be highly efficient for
axonal guidance,” Mohanty
said. “Our non-contact approach
shows remarkable capability
of non-invasively
navigating axons with 100 percent
efficiency and high spatiotemporal
resolution at large
working distance.”
Mohanty believes that this
new, optically-controlled method
will open new avenues for
non-invasive guidance of regenerating
axons at long working
distances for the restoration
of impaired neural
connections and functions. He
and his group, along with UT
Arlington assistant professor of
bioengineering Young-Tae
Kim, are working with the Veterans
Administration Spinal
Cord Injury Center in Dallas to
evaluate the technology as a
new option for the treatment of
spinal cord injuries.
A paper on the findings coauthored
by Mohanty, Kim,
visiting researcher Argha Mondal
and lead author Bryan
Black, was published in the July 1, 2013 edition of Optics Letters.
“The major goal of this project is to develop an effective, therapeutic approach
for robust guidance of regenerative axonal outgrowths past the glial
scar in the case of spinal cord injury,” Mohanty said.
M
ohanty’s group is also developing hybrid optical
methods of phototherapy. While use of light
alone has been beneficial in many applications,
there is a growing need to target light to diseased
tissue so that healthy tissue is not damaged.
Also, certain diseases – especially those
affecting the nervous system – require cell-selective
interaction with light. The recent development
of nanoparticles/genetic targeting in
combination with light irradiation is emerging as a new modality for hybrid
phototherapy, Mohanty said.
“We have developed new nanomaterials and employed existing light-activatable
molecules for various therapeutic applications such as cancer therapy,
restoration of vision and inhibition of pain,” he said.
Working with UT Arlington professor of physics Ali Koymen, Mohanty’s
lab developed a method using magnetic carbon nanoparticles to target and
destroy cancer cells through laser therapy - a treatment they believe could be
effective in cases of skin and other cancers without damaging surrounding
healthy cells.
Mohanty and Koymen co-authored a paper about the work along with Ling
Gu (lead author) and Vijayalakshmi Vardarajan, two postdoctoral researchers
in Mohanty’s lab, which was published in the January 2012 edition of the
Journal of Biomedical Optics.
“Because these nanoparticles are magnetic, we can use an external magnetic
field to focus them on the cancer cells. Then, we use a low-power laser
to heat them and destroy the cells beneath,” Koymen said. “Since only the carbon
nanoparticles are affected by the laser, the method leaves the healthy tis-
34 Maverick Science 2013-14