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Engineering Compartmentalized Optogenetic Protein Misfolding Stress Sensors
Author(s) -
Moore Christopher,
Santiago Sebasthian,
Lu Nancy,
Shoulders Matthew
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.882.11
Subject(s) - protein folding , unfolded protein response , endoplasmic reticulum , microbiology and biotechnology , optogenetics , proteostasis , protein aggregation , cytosol , biology , chemistry , biochemistry , neuroscience , enzyme
Protein misfolding in live cells is inherently linked to disease. Afflictions ranging from cancer to viral infection have been related to some form of dysregulation in the protein folding process. While a need exists to understand protein homeostasis in live cells, protein folding is typically studied with well‐established in vitro techniques that depend on a controlled environment and conditions that often stray from biological relevance. Since the current repertoire of in vivo techniques for studying protein folding is limited, we are interested in developing novel and convenient biochemical methods to quantify protein homeostasis inside live cells. Nature already utlilizes biomolecular stress‐response sensors localized to specific organelles to actively monitor protein homeostasis in a compartmentalized fashion. The specific aim of this project is to use chemical biology methods to retool natural cytosolic and endoplasmic reticulum (ER) unfolded protein sensors with bioluminescent or fluorescent proteins allowing users to monitor a bioluminescent resonance energy transfer signal that reports on protein misfolding stress in these cellular compartments. The development of these optogenetic sensors would allow researchers to use a convenient real‐time assay that simultaneously quantifies changes in the cytosolic and ER protein folding environments in live cells.