NSF Award
2426337
Understanding the molecular-level details of how cells communicate with each other provides critical insight into how living systems perform complex functions such as regulating metabolism, responding to stress, or learning. Naturally occurring peptides (e.g., neuropeptides and peptide hormones) are molecules which can act as messages to facilitate communication between cells in living systems. After being produced in the cell, most peptides undergo numerous molecular modifications that greatly impact their function. Despite their importance in biology, much about how peptides function, including the roles of their molecular modifications, are not well understood. This project will investigate the roles of an understudied modification that occurs in some peptides called amino acid isomerization, which generates molecules called D-amino acid-containing peptides. Amino acid isomerization changes the peptide’s three-dimensional shape, which can significantly affect the molecule’s biological function. The results from this project will provide critical information about how amino acid isomerization impacts cellular communication, which will improve our understanding of how living systems function. In addition to the advancements in basic science, this project will provide training to young scientists in interdisciplinary research to prepare these individuals for a wide range of careers, including those in industry, academics, or government. <br/><br/>Some post-translational modifications (e.g., phosphorylation) are well-studied and are understood to play critical roles in regulating protein function. This project focuses on enzyme-catalyzed amino acid isomerization, for which very little information is currently known. Specifically, this project will investigate how endogenous post-translational amino acid isomerization of cell-cell signaling peptides alters interactions with their cell surface receptor proteins. This will be accomplished through three research objectives. The first objective is to thoroughly characterize the role of amino acid isomerization for a known peptide-receptor interaction in Aplysia, an important model organism for understanding the molecular basis of learning, memory, and behavior. The second objective is to investigate amino acid isomerization in Platynereis, a model organism for understanding development and regeneration. The third objective is to build a library of predicted Aplysia neuropeptide G protein-coupled receptors and utilize this library to identify the receptors for known D-amino acid-containing neuropeptides. This project will provide new knowledge about how living systems alter their cellular communication via amino acid isomerization, a severely understudied chemical transformation.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
