A five-year, nearly $3.5 million grant to study the mechanisms of brain receptors involved in neurological disorders such as learning disabilities has been awarded to Vasanthi Jayaraman, PhD, of UTHealth Houston by the National Institutes of Health.
Jayaraman, professor and John S. Dunn Chair in Biochemistry and Molecular Biology with McGovern Medical School at UTHealth Houston, will build upon her years of research studying glutamate receptors – which ultimately control motor and cognitive functions in the central nervous system – in an effort to shed light on the pathologies of learning disabilities, epilepsy, and other neurological issues.
Communication between nerve cells serves as the basis of all brain activity. One of the fundamental steps involved in signal transmission between nerve cells is the conversion of a chemical signal liberated at the end of one nerve cell into an electrical signal at the second nerve cell. This step is mediated by a class of membrane-bound proteins known as neurotransmitter receptors. Glutamate receptors belong to this family of proteins.
The process of learning forms new connections, called synapses, between neurons in the brain. Signals sent across excitatory synapses increase the activity of the receiving neuron. Jayaraman’s team will analyze glutamate receptors during this transmission.
“These ‘on-switches’ are extremely critical for understanding processes like learning and memory,” said Jayaraman, who is also a faculty member at The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences. “The idea is to use this fundamental research to understand signaling in the brain and how this signaling process is altered in certain diseases and genetic mutations.”
Jayaraman’s laboratory studies the structural changes in glutamate receptors to learn how to better design therapies targeting this group of proteins.
Over the past 25 years, her team has tracked the movements of single molecules to reveal how proteins on the surface of nerve cells control gates that turn chemical signals into electrical signals. In 2017, the team worked with Rice University to gather the first experimental evidence detailing the dynamics of how one subtype of receptors, NMDA receptors, alter their shapes to control the sensitivity of the gate to chemical signals. The findings were published in Nature Chemical Biology. Previously, the researchers analyzed the conformations of a smaller and simpler, but related, system: the binding domain of another receptor, AMPA, which mediates fast signal transmission in the central nervous system.
With this latest round of funding, Jayaraman plans to focus more on the two other glutamate receptor subtypes: karinate receptors and delta receptors.
“We are building the foundation upon which other translational and clinical work will be based,” Jayaraman said.
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