Protein homeostasis in development and aging
We study the mechanisms that govern protein homeostasis in developmental processes and during aging using the powerful C. elegans model system
Our group is interested in protein homeostasis, or proteostasis, which corresponds to the capacity of cells and organisms to maintain the integrity of their proteome. Loss of proteostasis during aging is a major driver of cellular dysfunction, and many age-related diseases are characterized by pathological protein misfolding and aggregation. While the machineries that establish and maintain proteostasis are present in all cells, the rate of cellular aging and the phenotypes associated can greatly vary between cell types. Our research aims at understanding how proteostasis is orchestrated in different cell types in an animal.
Sala AJ, Grant RA, Imran G, Morton C, Brielmann RM, Bott LC, Watts J, Morimoto RI. “Nuclear receptor signaling via NHR-49/MDT-15 regulates stress resilience and proteostasis in response to reproductive and metabolic cues” (April 2023) bioRxiv doi 10.1101/2023.04.25.537803
Sala, A. J., and R. I. Morimoto. “Protecting the Future: Balancing Proteostasis for Reproduction.” Trends Cell Biol (Oct 12 2021). https://doi.org/10.1016/j.tcb.2021.09.009. https://www.ncbi.nlm.nih.gov/pubmed/34654604.
Bott, L. C., M. Forouhan, M. Lieto, A. J. Sala, R. Ellerington, J. O. Johnson, A. A. Speciale, et al. “Variants in Atp6v0a1 Cause Progressive Myoclonus Epilepsy and Developmental and Epileptic Encephalopathy.” Brain Commun 3, no. 4 (2021): fcab245. https://doi.org/10.1093/braincomms/fcab245. https://www.ncbi.nlm.nih.gov/pubmed/34909687.
Sala, A. J., L. C. Bott, R. M. Brielmann, and R. I. Morimoto. “Embryo Integrity Regulates Maternal Proteostasis and Stress Resilience.” Genes Dev 34, no. 9-10 (May 1 2020): 678-87. https://doi.org/10.1101/gad.335422.119. https://www.ncbi.nlm.nih.gov/pubmed/32217667.
Sala, A. J., L. C. Bott, and R. I. Morimoto. “Shaping Proteostasis at the Cellular, Tissue, and Organismal Level.” J Cell Biol 216, no. 5 (May 01 2017): 1231-41. https://doi.org/10.1083/jcb.201612111. https://www.ncbi.nlm.nih.gov/pubmed/28400444.