Molecular reporters for measuring proteostasis capacity in cells

本项目旨在开发荧光染料来报道未折叠蛋白负荷的变化，从而实时反映细胞在应激条件下的蛋白稳定状态。蛋白质平衡是细胞负责维持蛋白质的正确折叠和功能的内务过程。蛋白质稳定的扰动与神经退行性疾病有关，但化学探针不能测量细胞中的蛋白质稳定能力。预期的成果包括从机制上理解蛋白质错误折叠、聚集和蛋白质稳定之间的关系。预计这最终将有利于包括痴呆症在内的蛋白质折叠疾病的诊断，并提高生活质量。

This project aims to develop fluorescent dyes to report on the change in unfolded protein load, which reflects the proteostasis status in real time in cells under stress conditions. Proteostasis is a housekeeping process cells undertake to maintain the proper folding and functions of proteins. Perturbation of proteostasis has been linked to neurodegenerative diseases, but chemical probes cannot measure the proteostasis capacity in cells. Intended outcomes include a mechanistic understanding of the relationship between protein misfolding, aggregation and proteostasis. This is expected to ultimately benefit the diagnosis of protein folding diseases, including dementia, and improve the quality of life.