ביולוגיה של התא למתקדמים: תגובות תאיות לעקה בבריאות ובמחלות (0440.3125)

Perturbations to cellular homeostasis require integrative responses, involving multiple molecular mechanisms, for its restoration. Success or lack of success in this endeavor can be a central determinant between health and disease. Indeed, cellular responses to stress span the entire spectrum of cellular activities, from maintenance/alteration of chromosomal copy numbers to synthesis/turnover of all types of biological macromolecules (e.g. proteins). As such, the mechanisms involved in stress induction and/or its resolution are the subject of intense study and serve as targets for novel therapeutics. In this course, we will study the molecular mechanisms involved in such responses with emphasis on different sources of cellular stress, including toxic drugs, genetic diseases, protein misfolding and viral infection. In addition, we will expand on the experimental techniques involved in the study of cellular stress, and the model systems in which these phenomena are currently studied. 

The course is based on mandatory participation in weekly meetings during the whole semester. Each week will include a frontal lecture and active discussion based on prior obligatory reading of related papers.

The following topics will be covered:

Integrated Stress response (concept, key players, coordination), ER-stress and PERK pathway, 5'UTR-mediated translational control, translational control at the elongation level, physiological and pharmacological stressors, genetic mutations associated with stress (i.e., mitochondrial diseases and neurodegeneration), "Omics" methods to study gene expression responses to stress, stress granules, P-bodies, Genesis of unfolded protein response (UPR), chaperones, ER-associated degradation (ERAD), protein aggregation, IRE1 and ATF6 pathways, RIDD, RESET, misfolded protein diseases, late ER stress and apoptosis, therapeutic strategies. Large scale genomic responses to stress (aneuploidy, LOH, translocations), effect of stress on centromeres/kinetochores/microtubule organizing centers, effect on origin of replications and telomeres, Viral infection: a molecular battle of biosynthetic resources, viral infection-induced signaling programs that determine cell fate and infection outcome, cancer-induced alteration to cell responses, novel targets for immune- and viro-therapy.