What does a molecular thermometer look like? This seemed to be a simple question, not much different from the many science fair projects I had done in grade school and high school in Chicago. But rather than the simple solutions I’d present on triptych posterboards, the answer to this question has kept me fascinated for my entire career. The cell’s thermometer appears to be a network of stress-sensing transcription factors and specialized proteins—molecular chaperones—that function as the guardian of the proteome, sensing damage and keeping the cell’s proteins properly folded as they roll off the production line of ribosomes. Exciting as that was, none of us working on this question at the time could have predicted that this thermometer might also control the body’s fountain of youth and provide new ways of thinking about disease.
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