Title:Fibrillization and Liquid-Liquid Phase Separation of the Tau Peptide
Abstract: Intrinsically disordered peptides(IDP) are a special class of proteins that do not fold to a uniquethree-dimensional shape. These proteins play important roles in the cell, fromsignaling to serving as structural scaffolds. Under pathological conditions,they can self-assemble into structures that are toxic to the cell, and a numberof neurodegenerative diseases are associated with this self-assembly process.My talk will focus on the Tau protein, an IDP that binds to microtubules andcan form fibrillar aggregates, a process that has been linked with Alzheimer’sdisease. In addition to forming fibrils, the Tau protein can also phaseseparate into a protein rich and a protein depleted phase, a process known asliquid-liquid phase separation (LLPS). This process may play a protective rolein the cell against pathological fibrillization. I will present moleculardynamics and field theoretic simulations that map out the phase diagram for TauLLPS, and use this phase diagram to predict the conditions under which Tau canbe driven towards LLPS under live cell coculturing conditions.