Shining a LIGHT Samarendra Mohanty’s innovative biophysics research utilizes tools such as optical tweezers and light therapy as he and his students seek new and more effective ways to find and treat disease. By Greg Pederson Samar Mohanty, center, in his lab with doctoral students Bryan Black, left, and Kamal Dhakal. Brandon Wade 32 <strong>Maverick</strong> <strong>Science</strong> <strong>2013</strong>-<strong>14</strong>
B reakthroughs in technology are expanding the limits of what’s possible in biophysics research. Samarendra Mohanty is helping to push those boundaries by developing new tools to discover safer, more efficient ways to treat disease and study the human body. Mohanty, a UT Arlington assistant professor of physics, is using the principles of biophysics – studying biological processes and materials by means of the theories as well as the tools of physics – to find new and innovative ways to alter biological systems down to the molecular level. He and his students are improving cutting-edge tools such as optical tweezers, specialized optical microscopes and optogenetics (the science of controlling brain activity with light) to understand and influence processes in cells and cellular networks. “We have taken an integrated approach of cellular manipulation, activation and control by optical as well as hybrid approaches, combined with a variety of i<strong>mag</strong>ing methods to visualize and quantify responses in in-vitro and in-vivo models,” Mohanty said. “In order to evaluate miniscule changes to cell membranes during optical manipulation, we developed a unique multimodal i<strong>mag</strong>ing platform integrated with laser scissors, tweezers, spanners, transporters and stimulators here at UT Arlington.” At the moment, Mohanty and the Biophysics and Physiology Laboratory group he leads are working on projects in five major research areas, along with a number of smaller projects. He keeps up a relentless pace in preparing and submitting grant proposals which have brought millions of dollars in research support from the National Institutes of Health, National <strong>Science</strong> Foundation and other sources. He authors and co-authors manuscripts which are regularly published in top journals. “His projects are highly i<strong>mag</strong>inative. He’s doing an intriguing combination of physics, biology, chemistry and biomechanics,” said Alex Weiss, professor and chair of the Department of Physics. “He’s doing very interesting research with nerve cells and optical stimulation of the brain, among other things. The work his group is doing has a lot of potential to improve medical research and treatment of disease down the road.” A s excited as he is by his group’s current work, Mohanty is even more thrilled by the research he envisions happening in his lab in the years ahead. He wants to shift his main focus from different aspects of neuronal manipulation, i<strong>mag</strong>ing and control, to the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative, an effort unveiled by President Barack Obama in April <strong>2013</strong> which is intended to revolutionize understanding of the human brain through groundbreaking research. This i<strong>mag</strong>e shows a highly-controlled laser transfection of ChR2-YFP gene into a targeted area of retina (green is ChR2-YFP and blue is nuclei) by a near-infrared femtosecond laser microbeam. I<strong>mag</strong>e courtesy of Samarendra Mohanty. This illustration demonstrates the non-invasiveness of two-photon optogenetic stimulation. It shows brain tissue da<strong>mag</strong>e by an invasive fiber delivering one-photon stimulation (shown in blue) vs. non-invasive, two-photon stimulation (shown in red). Illustration courtesy of Samarendra Mohanty. One of Mohanty’s current projects which could be useful in the BRAIN initiative is the development of a tiny tool which could help scientists map and track interactions between neurons inside different areas of the brain. The fiber-optic, two-photon, optogenetic stimulator builds on a previous Mohanty discovery that near-infrared (NIR) light can be used to stimulate a light-sensitive protein introduced into living cells and neurons in the brain. This new method could show how different parts of the brain react when a linked area is stimulated. “Scientists have spent a lot of time looking at the physical connections between different regions of the brain. But that information is not sufficient unless we examine how those connections function,” Mohanty said. “That's where two-photon optogenetics comes into play. This is a tool not only to control the neuronal activity but to understand how the brain works.” The two-photon optogenetic stimulation involves introducing the gene for ChR2, a protein that responds to light, into a sample of excitable tissue cells. A fiber-optic infrared beam of NIR light can then be used to precisely excite the neurons in a tissue circuit. In the brain, researchers could then observe responses in the excited area as well as other parts of the neural circuit. In living subjects, scientists could also observe the behavioral outcome, Mohanty said. Optogenetic stimulation avoids da<strong>mag</strong>e to living tissue by stimulating neurons with light instead of electric pulses used in past research. Mohanty’s method of using low-energy NIR light also enables more precision and a deeper focus than the blue or green light beams often used in optogenetic stimulation. Kamal Dhakal, a third-year doctoral student in Mohanty’s lab, works in optogenetics and optical manipulation of cells. He says the multidisciplinary approach of Mohanty’s research is preparing him well for a career in optics and biophotonics. Dhakal was lead author of a paper on the brain mapping research that was published in the June 1, <strong>2013</strong> edition of the journal Optics Letters; Mohanty, doctoral student Bryan Black and postdoctoral researcher Ling Gu were co-authors. “Dr. Mohanty is very good researcher and has fancy ideas and visions,” Dhakal said. “He is very frank, like a friend, and helpful. Before joining his lab, I did not have any technical knowledge such as using computer software for data analysis, interfacing instruments with computers, i<strong>mag</strong>ing, programming, even how to make a good graph. But today, I know all of them. In addition, my projects require a wide variety of knowledge, from genetics to optics, mammalian cells to bacterial cells, electrophysiology to digital holography. These <strong>Maverick</strong> <strong>Science</strong> <strong>2013</strong>-<strong>14</strong> 33
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