Proteome metastability at the edge of cellular health and age-associated protein aggregation 

Seminar Details

Host: BGA (Amelia Brave)

Time: 4:00 pm- 5:00 pm

Location: BICH 108

Seminar Abstract

The ability to maintain a stable proteome is essential for cellular health and organismal lifespan against the myriad of challenges from biochemical and physiological stress, the effects of aging and the hundreds of diseases associated with protein misfolding.  These events are regulated  by the Proteostasis Network (PN) of ~3,000 genes that determine protein synthesis, folding and assembly, localization and degradation. The properties of the PN are imbalanced by the expression of highly aggregation-prone proteins that can cause a dramatic increase in overall metastability, with the expression of even a single missense temperature sensitive mutant protein causing hundreds of proteins to become conformationally unstable. Aging, however, appears to have the most dramatic consequence on protein instability affecting 1/3rd of the proteome in C. elegans resulting from the repression of the heat shock response and expression of chaperones in early adulthood. Our current efforts are to identify when in aging these events occur and to develop strategies to prevent or delay proteome failure to enhance cellular healthspan and to prevent protein conformational diseases.