Cornell University

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C&CB Seminar Joan-Emma Shea (UCSB)

Monday, February 19, 2024 at 4:00pm

Baker Lab, 119
259 East Ave, Ithaca, NY 14850, USA

“Self-Assembly of the Tau Protein: Liquid-Liquid Phase Separation and Fibrillization”

Tau is an intrinsically disordered protein that plays an important role in stabilizing microtubules. Under pathological conditions, this protein can also self-assemble into fibrillar structures, a process that has been associated with a class of neurodegenerative diseases known as Tauopathies. Interestingly, this protein is also capable of assembling into liquid droplets through a process of liquid-liquid phase separation (LLPS). Using a combination of field-theoretic simulations, coarse-grained models, and atomistic simulations, we present an investigation of the mechanisms of fibrillization and phase separation of this protein. We investigate fragments of Tau that have a propensity to either phase separate or form fibrils, enabling us to shed light into the sequence characteristics linked with these two modes of assembly. Finally, we introduce a 19-residue fragment of Tau that is capable of seeding the fibrillization of full-length Tau, and we discuss the effect of point mutations in modulating aggregation in familial forms of Tauopathies.

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Chemistry and Chemical Biology

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Lori Ferrier

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Joan-Emma Shea

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