EAGER: Engineering Molecular Sensors Of Endoplasmic Reticulum-Associated Degradation (ERAD)

William Marsh Rice University, Houston TX

Investigators

Abstract

This NSF award by the Biotechnology, Biochemical and Biomass Engineering program supports the development of novel tools that will aid researchers in the discovery of enhancers of degradation of misfolded proteins that are processed by cells. The degradation of misfolded proteins is important both in bioprocessing and in medicine, as one of the biggest problems in expression of certain recombinant therapeutic proteins is the intracellular aggregation of these proteins. Proteins which are targeted for secretion that accumulate as aggregated or misfolded proteins inside cells cause cellular stress and eventually cell death via apoptosis, leading to loss of productivity in bioprocessing applications. In diseases such as Alzheimer's or Parkinson's, the presence of an aggregated protein appears to lead to neurodegeneration. In protein misfolding diseases, endoplasmic reticulum or ER stress may play a role in cell death. The enhancement of mechanisms which would lead to degradation of those proteins might slow down the progression of disease. In this project, the investigators propose to develop a novel fluorescence based assay for the detection of the activation of a specific protein degradation pathway (ER-degradation). This assay is the first step in being able to develop high throughput screens for molecules that will enhance intracellular degradation of misfolded proteins. The assay will have applications both in the bioprocessing industry and in biomedicine. The PI will integrate research and education at the graduate and undergraduate levels, and work to increase the diversity of the biotechnology field.