北京大学定量生物学中心
学术报告
题 目: Unlocking the secrets of proteostasis: Does a 12-hour oscillator hold the key to treating neurodegeneration?
University of Pittsburgh School of Medicine
时 间: 6月24日（周一）13:00-14:00
地 点: 吕志和楼B101
主持人: 汤超 教授
摘要:
Proteostasis, the cellular mechanism that governs the synthesis, folding, and degradation of proteins, is crucial for maintaining proteome integrity, especially under proteotoxic stress. A decline in protein quality control is closely linked to aging and neurodegenerative diseases. Traditionally, proteostasis was believed to be constant under basal conditions. However, using novel mathematical tools, our lab has uncovered a surprising 12-hour rhythm in global proteostasis dynamics in normal cells, operating under physiological conditions. This 12-hour rhythm is regulated by a cell-autonomous mammalian 12-hour ultradian oscillator, independent of the 24-hour circadian clock and the cell cycle. In this talk, I will present our latest research on the gene regulatory network, chromatin and epigenetic landscape, biological function, and evolutionary origin of the 12-hour oscillator. I will further highlight our recent discovery of the critical role of nuclear speckle liquid-liquid phase separation in controlling proteostasis. Furthermore, I will discuss innovative strategies for rejuvenating nuclear speckles to combat protein misfolding diseases, such as tauopathy in neurodegeneration.
Bokai, a native of Beijing, China, earned his B.S. degree from Peking University. He then pursued his Ph.D. at Pennsylvania State University, followed by post-doctoral training with Dr. Bert W. O’Malley at Baylor College of Medicine in Houston, USA. During his tenure at Baylor, Bokai was promoted to the position of instructor as a junior faculty member. His research there focused on the molecular mechanisms regulating circadian rhythms and the interplay between circadian rhythms and hepatic cellular metabolism. Recently, Bokai discovered a novel mammalian 12-hour clock that operates independently of the circadian rhythm, coordinating cellular stress responses with metabolism. In September 2018, he joined the Aging Institute at the University of Pittsburgh School of Medicine to establish his independent lab and continue his research on the 12-hour oscillator. Bokai has received several prestigious awards for his work on the 12-hour oscillator in aging and metabolism, including the NIH Director's New Innovator Award in 2020 and the Hevolution/AFAR New Investigator Award in Aging Biology and Geroscience in 2024. He has also presented his research at prominent international conferences, such as the EMBL Symposium on biological oscillators and the Cold Spring Harbor Laboratory Symposium on proteostasis. For more details, please visit https://bzhulab.com/.
