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Date of Award
Bachelor of Science (BS)
Department of Biology
Cells experiencing misfolded protein stress can become debilitated and die, contributing to the onset of disease. The nascent polypeptide-associated complex (NAC) is a heterodimeric translational chaperone that protects against misfolded protein stress by mediating proper protein folding and localization during translation. Depletion of this complex results in misfolded protein accumulation in the endoplasmic reticulum (ER). To determine the importance of the NAC to proteostasis, we have previously depleted the complex in C.elegans via RNA interference and observed numerous dose-dependent effects, including apoptosis of neuronal cells and changes in gene expression of hypodermal cells. While we have observed these cell-specific responses to misfolded protein stress by depleting the NAC artificially, we are also investigating the state of the NAC in cells undergoing misfolded protein stress faced in biologically relevant conditions. Preliminary studies indicate that the beta subunit of the NAC is cleaved in worms undergoing chemically and heat induced misfolded protein stress putatively at a caspase cleavage site functionally conserved in other organisms. We are determining if this cleavage is a step in the apoptotic cell death triggered by misfolded protein stress and therefore dependent on the core elements of the C. elegans apoptotic pathway. By understanding the cell-specific responses to misfolded protein stress induced by NAC depletion in combination with the fate of the NAC in the face of chemically induced stress, we hope to elucidate the role of this highly conserved complex in proteostasis and biologically relevant cell survival.
Gerber, Monica, "Analyzing the effect of apoptotic mutations on the state of the nascent-polypeptide associated complex in Caenorhabditis elegans" (2019). Senior Honors Projects, 2010-current. 673.