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This lecture by the instructor delves into the changing landscape of proteome foldedness, aggregation, and conformation under proteostasis stress. The presentation covers protein aggregation in neurodegenerative diseases, the impact of aggregation on cell biology, and the susceptibility of metastably-folded proteins to aggregation. Strategies to measure stress-induced proteome aggregation, protein solubility changes, and the role of protein quality control networks are discussed. The lecture explores how proteostasis stress affects the aggregation state of the proteome and the potential collapse of proteostasis. The study of mutant proteins altering proteome solubility before and after inclusion formation is also presented.