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College 8 Seminar | Client folding in biomolecular condensates - Pr Simon Ebbinghaus

From Monday October 06, 2025 at 10:00 am to Monday October 06, 2025 at 12:00 pm

"Client folding in biomolecular condensates"

 

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Biomolecular condensates such as stress granules (SGs) are central to cellular organization and regulation, but their dysregulation is linked to neurodegenerative diseases. SGs transiently sequester misfolded proteins, including Superoxide Dismutase 1 (SOD1), a protein whose aggregation is a hallmark of amyotrophic lateral sclerosis (ALS). Yet, it remains unclear how SGs influence SOD1 stability and aggregation. To address this, we developed confocal Fast Relaxation Imaging (cFReI), which employs infrared laser–induced temperature jumps to monitor unfolding and aggregation kinetics of SOD1 within living cells. By comparing SOD1 dynamics inside SGs and in the surrounding cytoplasm, we found that SG association does not destabilize SOD1. Instead, many cells displayed a modest stability increase within SGs. These findings indicate that SGs primarily function as passive reservoirs for misfolded proteins, rather than promoting their destabilization or aggregation, providing new insight into their role in protein homeostasis and disease progression