EPSCoR Research Fellows: NSF: Building Mechanistic Models for the Interaction of Tau Protein and Neuronal Voltage

Middlebury College, Middlebury VT

Investigators

Abstract

This Research Infrastructure Improvement EPSCoR Research Fellows project provides a fellowship to an Assistant Professor and training for undergraduate students at Middlebury College. This work is conducted in collaboration with Veronica Ciocanel at Duke University. Through the fellowship, the principal investigator (PI) will develop mathematical models to describe the accumulation of both healthy and pathological tau protein in brain cells, as seen in neurodegenerative diseases such as Alzheimer’s Disease. The project will unite experts in intracellular transport and mathematical modeling of neuronal behavior to propose mechanisms underlying changes in neuron activity observed at different stages of the disease. This work will give the PI and undergraduate students hands-on experience with cutting-edge mathematical and computational tools, and the results will be shared through student mentorship and public presentations to broaden understanding of brain health and disease. In certain neurodegenerative diseases known as tauopathies, communication across brain regions breaks down due to the accumulation of a pathological form of the protein tau inside neurons, disrupting normal activity and ultimately leading to cell death. Experimental studies suggest a two-way relationship: pathological tau affects neuron activity, and changes in neuron activity can, in turn, influence the accumulation of both pathological and healthy tau. However, the mechanisms underlying this interdependence remain poorly understood. This project will develop a mathematical modeling framework that integrates the intracellular dynamics of tau accumulation with neuronal voltage behavior. The goal is to create experimentally informed models capable of predicting how pathological tau buildup, neuronal electrical activity, and intracellular transport interact. This fellowship will serve as a critical foundation for future development of large-scale models that simulate the spread of pathological tau through neuronal networks. It will also provide undergraduate students with training in advanced mathematical and computational techniques, equipping them to make meaningful contributions to this research. This project is supported by the EPSCoR Research Infrastructure Improvement Program: EPSCoR Research Fellows, which supports early- and mid-career investigators in eligible jurisdictions to develop collaborations at the nation’s private, government or academic research institutions. 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.