Identification of Small Molecules that Interact with NPas4, a Regulator of Inhibitory Synapse Development
Mentors: Jon Madison and Catherine Luce, Stanley Center Psychiatric Disease Initiative
We focused on identifying small molecules that regulate Npas4, a regulator of inhibitory synapsis development that could in turn regulate the excitatory and inhibitory balance in the brain. This balance has been hypothesized as important for proper brain function; research suggests that several cognitive and psychiatric diseases are associated with a change in the balance of excitation/inhibition (E/I balance). We screened over 20,000 compounds with Npas4 through small-molecule microarrays (SMMs) and confirmed interactions with surface plasmon resonance (SPR). Future experiments will examine the ability of these molecules to functionally regulate Npas4 and inhibitory synapsis development in primary neurons. We hope these small molecules can serve as chemical probes to further understand cognitive and mood disorders and the contribution of E/I balance to the cause of these diseases.
"I was a little star-struck this summer: the greats of our generation in health and human biology ride the same elevator as you every morning. They sit across from you to discuss how you might aspire to be as great as they are one day, and they don’t use gimmicks to sway you to science. To them it’s all about following their hearts, those burning questions, and the idealistic dream of curing disease.”
Seanna Pieper-Jordan is a sophomore at Yale University who is majoring in biology and ethnicity, race, and migration. She discovered a common scaffold that recognizes Npas4, a regulator of inhibitory synapses development.