NSF Funds Project to Make Better Computer Simulation of Nerve-muscle Communication

NSF Funds Project to Make Better Computer Simulation of Nerve-muscle Communication
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A $750,000 grant from the National Science Foundation will fund a project to build a better computer model of the communication between nerves and muscle cells.

The project may have applications for Lambert-Eaton myasthenic syndrome (LEMS), a condition in which the immune system disrupts nerve-muscle communication.

Nerve cells use electricity to send signals from one part of the cell to the other. When a neuron is activated, ion channels in the cell’s membrane open and allow electrically charged ions to flow in and out. This ultimately creates a sharp rise and fall in voltage that forms the base of how an action potential makes information travel down a nerve fiber and reach other cells via neurotransmitters.

The new project will build on previous work, in which researchers used software called MCell to create a computer simulation of a neuron and a muscle cell. Using supercomputers, this prior analysis was able to simulate how factors such as the location of certain proteins affected the release of neurotransmitters from nerve terminals to the muscle.

However, MCell has a limitation; it cannot account for changes in action potential that prompt neurotransmitter release while the cell is active.

“Any little change in the form of the action potential can cause a very different probability of neurotransmitter release,” Rozita Laghaei, PhD, a scientist at the Pittsburgh Supercomputing Center, said in a press release.

Laghaei is one of the principal investigators in the new grant, along with Stephen Meriney, PhD, a professor of neuroscience at the University of Pittsburgh. Robert Poage, PhD, of the University of North Carolina at Pembroke, and Thomas Blanpied, PhD, of the University of Maryland School of Medicine, also will be collaborating.

One aim of the new project is to merge MCell with another software, called NEURON (developed at Yale University), which is able to simulate changes in action potentials.

“During our earlier simulations, the action potential was constant; it’s not possible right now for MCell to alter action potentials on the fly,” Laghaei said. “NEURON is capable of calculating changes in an action potential during activity in the cell. We’re going to combine those two to make a new computer modeling approach that combines models of action potentials with models of nerve terminal structure and organization. [We will create] a realistic, 3D nerve terminal model with a voltage simulator that predicts the effects of these ion fluxes on the shape of action potentials,” she said.

The project may have immediate applications in LEMS, which is caused by the immune system mistakenly attacking ion channels — specifically calcium channels — at nerve endings, which impairs neuron-to-muscle communication.

Amifampridine, marketed as Firdapse and Ruzurgi, is an approved LEMS therapy that works by targeting potassium channels on neurons and extending action potentials.

“While [amifampridine] is helpful, our studies show that [patients] might benefit from a combination therapy … with a new calcium channel drug, called GV-58, that we are developing,” Meriney said.

Early experiments have indicated that combining GV-58 with amifampridine has a greater benefit than either treatment alone.

However, the optimal mixture of the medications still needs to be determined.

Because such tests in animal models are costly, complicated, and time-consuming, a major goal of the new project is to examine various levels of these therapies in the computer simulations. Results may be used to inform the design of future animal studies and, eventually, possible studies in people.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
Total Posts: 6

José holds a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.

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Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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