Excellence in research: probing DJ-1 as a hub for calcium dynamics in neuronal plasticity

The National Science Foundation awarded North Carolina Agricultural and Technical State University $1.255 million on August 1, 2026, under the Biological Sciences program (CFDA 47.074) to investigate how the RNA-binding protein DJ-1 regulates calcium homeostasis and synaptic plasticity through control of local protein synthesis and protein stability in neurons.

The research addresses fundamental mechanisms of learning and memory by examining how DJ-1 coordinates calcium signaling in neurons and influences learning-related processes. The project aims to advance understanding of how disruptions in calcium signaling and protein production contribute to neurodegenerative disorders, including Alzheimer's disease and other cognitive impairment, and to identify potential therapeutic targets. The work is performed in Greensboro, North Carolina, with a period of performance from August 1, 2026, through July 31, 2029.

The award integrates research, education, and outreach activities that provide hands-on neuroscience research training to undergraduate students, graduate students, and future STEM educators. By expanding research and educational capacity at NC A&T, the project expands participation in neuroscience and prepares a workforce with interdisciplinary expertise in molecular neuroscience, quantitative data analysis, and modern biomedical research methodologies.

Abstract

Learning and memory depend on the ability of nerve cells to modify the strength of their connections. These changes require precise control of calcium signaling and protein production. Disruptions in these processes contribute to neurological disorders, including alzheimer's disease and other forms of cognitive impairment. This project investigates how the multifunctional protein DJ-1 coordinates calcium signaling in neurons and influences learning-related processes, advancing fundamental understanding of how brain cells communicate during learning and memory. The knowledge generated by this research may provide new insights into the biological mechanisms underlying neurodegenerative disorders and identify potential targets for future therapeutic development. Through integrated research, education, and outreach activities, undergraduate students, graduate students, and future stem educators will receive hands-on training in neuroscience research. By expanding neuroscience research and educational capacity at north carolina agricultural and technical state university, the project expands participation in an important field and prepares a workforce for careers in science and education. The project also advances NSF priorities in biotechnology by generating fundamental knowledge of cellular signaling mechanisms and by preparing trainees with interdisciplinary expertise in molecular neuroscience, quantitative data analysis, and modern biomedical research methodologies. This project serves the national interest by advancing scientific discovery, promoting health and well-being, and strengthening the nation's stem workforce. This project investigates how the RNA-binding protein DJ-1 regulates calcium homeostasis and synaptic plasticity through control of local protein synthesis and protein stability in neurons. Building on preliminary evidence that DJ-1 functions as a translational regulator of calcium channel expression, the project will test the hypothesis that DJ-1 coordinates the translation and stability of three highly expressed calcium channels, namely, L-type voltage-gated calcium channels, inositol 1,4,5-trisphosphate receptors, and ryanodine receptors to regulate neuronal plasticity. Three objectives will be pursued: (1) determine whether DJ-1 regulates intracellular calcium channel expression in a region-specific manner; (2) define how DJ-1 controls calcium signaling and metabotropic glutamate receptor-dependent synaptic plasticity through translational regulation and protein-protein interactions; and (3) test whether modulation of DJ-1 restores synaptic plasticity and neuronal excitability in a mouse model of cognitive impairment. The project integrates molecular biology, proteomics, transcriptomics, imaging, and electrophysiological approaches to directly examine compartment-specific regulation of neuronal proteostasis. The anticipated outcomes will establish new mechanistic insights into how RNA-binding proteins coordinate local calcium signaling and synaptic function, providing a broader framework for understanding cellular signaling and plasticity in the nervous system and other biological systems. 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.- subawards are planned for this award.