National Institute of Neurological Disorders and Stroke 5U54NS123985-05

Core B: Macromolecular and Cellular Structure Core

Award to University of California, San Francisco to support the Macromolecular and Cellular Structure Core using cryoEM and biochemical assays to study tau metabolism and degradation, aiming to identify therapeutic targets for brain disorders.

Description

The primary objective of the Macromolecular and Cellular Structure Core is to provide cutting edge, innovative platforms for structural characterization responsive to needs and discoveries of the U54 FTD Center without Walls. The long-term goal is to understand the overall metabolism of tau, how it is stabilized by chaperones and cochaperones, and how it is channeled for degradation by the lysosome. The core will use cryoEM methodologies to determine atomic resolution structures of relevant proteins and complexes, provide cellular context for tau lysosomal degradation via cryoEM-Tomography, and quantify tau seeds via RTQuiC assays. These efforts aim to reveal mechanisms of tau turnover and identify therapeutic targets.

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