Current topics in proteostasis: Synthesis, folding and degradation of proteins

BCH 2024H

In landmark review articles published in Science (Science 2008 319:916) and Annual Reviews in Biochemistry (Annu Rev Biochem 2009 78:959), a group of important leaders in protein folding and misfolding mapped out the idea of proteostasis, conceptualizing ways in which maintenance of a healthy proteome could be manipulated to slow aging or cure disease. They conceived of a so-called “proteostasis boundary”, a theoretical edge that envelopes all the proteins in a healthy, unstressed cell based on three dimensions— their stability, rate of folding, and rate of misfolding. The position of the proteostasis boundary within this three-dimensional space, is defined by regulators of protein translation, protein folding factors such as molecular chaperones, antioxidant enzymes, and protein degradation machinery including the ubiquitin/proteasome system and autophagy pathways. Responses to proteotoxic stress act to expand the proteostasis boundary while aging and various disease states act to contract the boundary or move certain proteins outside the boundary resulting in degenerative disease. This is a powerful idea that has seen a strong growth in the scientific literature over the last decade (1 paper in 2007 to about 450 papers in 2017). In this course we will address topics derived from recent literature and explore both basic and applied aspects of proteostasis research.

Course Next Offered

Fall 2018

Course Time and Location

Wednesday, September 5 1:30 - 3:30 pm MaRS West Tower Rm 1623
Wednesday, September 19 1:30 - 3:30 pm MaRS West Tower Rm 1623
Wednesday, September 27 1:30 - 3:30 pm MaRS West Tower Rm 1623
Wednesday, October 17 1:30 - 3:30 pm MaRS West Tower Rm 1523
Wednesday, October 24 1:30 - 3:30 pm MaRS West Tower Rm 1623
Wednesday, October 31 1:30 - 3:30 pm MaRS West Tower Rm 1623

Enrollment Limit

Yes — 10

Method of Student Evaluation

Format:
Introductory material will be available on-line prior to the start of the course.
During the first session the coordinator will provide background and context for various topics— a “Cole’s notes” overview.
For subsequent sessions, students will work in groups, with guidance by the coordinator, to analyze papers, present a synopsis of the main findings and lead a discussion on the significance of the work. Students will be asked to present more than once during the course. Non-presenting students will be required to read the papers and submit a short, 500 word, critical reflection paper* prior to class. Grading scheme: 50% based on presentations/50% based on reaction/reflection papers.

*Note: A critical reflection paper is a brief statement of your personal and intellectual reaction to the reading that involves reflecting on what you learned and how it relates to previous knowledge, how the paper might stimulate new interests, what was unclear or puzzling about the paper, and compiling a short list of questions worth discussing in class. This is distinct from a “scientific critique” which would require far more rigorous analysis of the elements of the paper.

Coordinator

John R. Glover

John R. Glover

Rm 1616 MaRS West Tower
416-200-5985
john.glover@utoronto.ca

Last Updated 31 July 2018