A novel type of proteasome condensates that can target toxic protein aggregates

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• Dr Yu Ye, Imperial College London, Department of Brain Science
• Friday 01 March 2024, 16:00-17:00
• Seminar Room (Level 2), Dept of Pharmacology .

If you have a question about this talk, please contact Daniel Paolo Juan.

Dr Yu Ye

Imperial College London, Department of Brain Science

Biography

Yu completed his PhD training in David Komander’s lab at MRC -LMB, where they combined structural biology with biophysical techniques to study molecular details of ubiquitin chains and deubiquitinases, and interactions that underlaid regulation of the ubiquitin-proteasome system (UPS). Following this, Yu was fortunate to secure a stipendiary Junior Research Fellowship at Selwyn College followed by a Sir Henry Wellcome Research Fellowship, to study the UPS with super-resolution imaging techniques. They worked between David Klenerman’s group at Cambridge and Daniel Finley’s group at Harvard to establish their own research direction, focusing on using the UPS to remove protein aggregates. Notably, their group demonstrated that large fibrillar aggregates can be directly broken up by the 26S proteasome holoenzyme into small fragments in vitro in a ubiquitin-independent manner, defining a novel, fibril-fragmenting function of proteasomes (Cliffe et al., Cell Rep. 2019).

During this time, they also served as a Fellow and Director of Studies in Natural Sciences at Selwyn. With a generous start-up package, they moved to Imperial College London to study the interplay between UPS and protein aggregation in neuronal models. Recently, their group developed a quantitative super-resolution imaging approach to measure the ability of pathological aggregates to penetrate cells, showing that proteasomes respond to proteotoxicity within hours, leading to aggregate removal (Morten et al.,PNAS 2022). They are now expanding these findings to characterise mechanisms underlying this aggregate-induced proteasome response, which we think is driven by condensation of proteasomes and specific protein factors.

Venue: Level 2 Seminar Room

Zoom Link: https://cam-ac-uk.zoom.us/j/89654824601?pwd=QU9QNEVHVkJSR0dVeVZ4VmovV2Uydz09

Meeting ID: 896 5482 4601

Passcode: 482026

This talk is part of the Department of Pharmacology Seminar Series series.

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