Description: The integrated stress response (ISR) is an intracellular signaling program that is required for an organism to adapt to a variable environment and maintain health. In response to a variety of environmental and pathological conditions, including protein homeostasis (proteostasis) defects, nutrient deprivation, viral infection, and oxidative stress, the ISR restores balance by reprogramming gene expression. The various stresses are sensed by four specialized kinases that converge on phosphorylation of a single serine on the eukaryotic translation initiation factor eIF2 (gene = EIF2S1). eIF2 phosphorylation blocks the action of eIF2’s guanine nucleotide exchange factor termed eIF2B, resulting in a general reduction in protein synthesis. At the same time, phosphorylation of eIF2 also triggers the translation of specific mRNAs, including key transcription factors, such as ATF4. As such, the mechanistic underpinnings of this stress response network lie solidly in the world of post-transcriptional gene regulation at the translational level. This course will delve into the mechanism and methodology behind this essential stress response pathway, aberrations in which cause a myriad of diseases.
Structure: Lectures and student presentations
Outcome: Through lectures, assigned readings, class presentations and discussions, and individual inquiry, students will gain:
- A graduate-level understanding of how cells activate and execute the ISR.
- Familiarity with experimental methods and tools that are used to study the ISR in cells and in animals.
Grading: A total of 200 points may be earned in this course. Attendance and participation are worth 80 points (10 points per class session). Student presentation of a research paper is worth 70 points. A final project is worth 50 points. The final project consists of a concise (1-page) written report that requires answering a qualifying exam-type question based on a literature search and identification of lynchpin experiments.
Course Materials: A collection of review articles and research papers will be located in the Canvas course platform.