Lysosome Regulation and Signaling in Aging and Alzheimer's Disease

This is an equipment supplement application for a Program Project Grant (P01AG066606, June 1, 2021-February 28, 2026, PI: Zheng, Hui). The overarching goal of the parent P01 is to investigate the lysosome-to-nucleus signaling pathways regulating lysosomal homoeostasis in aging and Alzheimer’s disease. The P01 consists of three highly interactive projects and two scientific cores, which are overseen by an administration and data integration core. One of the essential components of the P01 is Project 2: A TFEB and V-ATPase-mediated lysosomal stress sensing pathway in tauopathy. The overarching goal of this project is to investigate a Tau-induced TFEB lysosome-to-nucleus signaling pathway regulating lysosomal homeostasis and cellular clearance in physiological and tauopathy conditions and to identify strategies to augment this pathway for enhanced cellular clearance. This project uses in vitro culture systems and mouse models and requires extensive immunofluorescence staining and microscopic imaging. We have relied on our existing EVOS FL Auto microscope for this purpose but it is currently out of order. Unfortunately, this model was discontinued in 1Q 2019 and replaced by EVOS M7000. Starting 2024, this model was no longer serviceable by the company. Therefore, we are in need to purchase a new EVOS M7000 microscope with Onstage Incubator to replace the EVOS FL Auto. This is essential to continue with the studies proposed in Project 2 of the P01. We have discussed the need with Dr. Barrett who advised us to apply for an equipment supplement.