Genetic Engineering & Biotechnology News

JUN15 2018

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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10 | JUNE 15, 2018 | Genetic Engineering & Biotechnology News | Lighting Up the Heart Continued from page 1 But it was another property of graphene that interested Alex Savtchenko, a Ph.D. biophysicist and his colleagues at the UCSD School of Medicine, along with his collaborator, biophysicist Elena Molokanova, Ph.D., CEO of Nanotools Bioscience: the fact that graphene efficiently converts light to electric charge. Dr. Savtchenko wondered if this could be exploited as a means to control the electrical activity of cells such as neu- rons or cardiomyocytes, heart muscle cells. Cultured cardio- myocytes typically beat at their own rate in a petri dish, Dr. Savtchenko explains. What if graphene could be used to pho- toelectrically pace the cells cultured on it? As described in a paper in the May 18 issue of Science Advances, Dr. Savtchenko's team found exactly this effect— after culturing cardiomyocytes on sheets of graphene, they discovered they could shine a light on the graphene and elicit an action potential, a "beat," in the cultured cells. What's more, they could control the rate of beat by in- creasing or decreasing the intensity of the light, an effect Dr. Savtchenko said drew a crowd of grad students and research- ers from neighboring labs. "I was able to actually turn the light and cells like puppies would run faster and you turn that knob up or down, and they run even faster or slower," he says. "People gathered around asking, 'Can I turn the knob so I can see this with my own eyes?'" Elegant Effect The elegance of such an effect, in a biological experiment, is impressive, says Calum MacRae, M.D., Ph.D., associate professor at Harvard Medical School and until recently the chief of cardiovascular medicine at Brigham and Women's Hospital, and it's a discovery that could offer new avenues to researchers interested in how electrical impulses modulate cell behaviors. "There is a beautiful linearity of response," he says. "It's a nice example of how materials science can really begin to have us change the way we think about what we do in biol- ogy and biomedicine and they are to be congratulated." That was part of the aim going into the study, according to Dr. Savtchenko. While other techniques exist for modu- lating the electrical activity and signaling of cells, such as direct electrical stimulation or optogenetic techniques, he says, many of those alter the cells in some fashion. His team was looking for a less-invasive method "to elicit some kind of response without perturbing what the cells are supposed to do." Cardiomyocytes, like neurons, typically maintain a rest- ing potential of around –70mv to –90mv across the cell membrane, i.e., their interior is more negatively charged than their exterior. When a cell is depolarized to a sufficient de- gree, say between –70mv to –50mv, it triggers an action po- tential, the beating of heart cell or an electrical impulse down a neuron's axon. Optically stimulated graphene produces excited, nega- tively charged electrons, which through capacitive charge transfer make the extracellular environment more negative, effectively depolarizing the cells and inducing an action po- tential, Dr. Savtchenko says. Moreover, he adds, all human cells in the body exist in an electrically conductive environment, so graphene can provide both basic researchers with a more realistic and controllable tissue model. Outside basic research, he sees initial applica- tions for the new technology in both tissue engineering and drug testing and discovery. If you want to test a new anti-arrhythmia or anti-tachy- cardia drug, for instance, current techniques involve cultured cardiomyocytes that are contracting at their own rate. Gra- phene could provide a way to pace cardiomyocytes to the exact state the drug is intended to treat. "We can actually cre- ate a cardiac arrest with these cells," Dr. Savtchenko says. "If you apply a lot of light, the cells contract faster and faster… Drug Discovery Illustration of the atomic-scale molecular structure of graphene, a single hexagonal layer of graphite. It is composed of hexagonally arranged carbon atoms linked by strong covalent bonds. Graphene is strong and flexible and transports electrons highly efficiently. Alfred Pasieka/Science Photo Library/Getty Images Researchers at the University of California San Diego say they have identified a key factor that partially unravels nucleosomes and thus opens the way for genes to activate. The identification of NDF, or nucleosome destabilizing factor, is described ("NDF, a Nucleosome Destabilizing Factor That Facilitates Transcription through Nucleosomes") in Genes & Development. The scientists say the finding provides a new perspective on how genes are turned on and off—knowledge useful in the study of human diseases such as cancer, which can be caused by improper gene activity. "It's a special privilege to discover a new activity in the regulation of our genes," said James Kadonaga, Ph.D., Distinguished Professor of Molecular Biology and the Amylin Endowed Chair in Lifesciences Edu- cation and Research, adding that the breakthrough came as a result of postdoc Jia Fei's interest in factors that might disassemble or destabilize nucleosomes. "This novel approach led to the identification of NDF as a nucleosome destabilizing factor." When genes are turned on, RNA polymerase travels along the DNA and makes a working copy (RNA) of the DNA. Here, nucleosomes, which look like beads on the DNA chain, pose a problem because they block the passage of the polymerase. This led to the question: How is the polymerase able to travel through nucleosomes? The answer emerged with the identification of NDF, which destabilizes nucleosomes and enables the progression of the polymerase. The researchers say NDF's makeup suggests that it is broadly used in perhaps all human cells and may play a role in disease. "NDF is present at abnormally high levels in breast cancer cells, and the overproduction of NDF might be partly responsible for the uncontrolled growth of these cells," continued Dr. Kadonaga. "Thus, the iden- tification of NDF resolves an old mystery and reveals a new factor that may have an important role in many aspects of human biology." n NDF Identified as Critical Molecule for Facilitating Transcription through Nucleosomes

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