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    • 72678 The Life and Death of Proteins 2014
    • 72678 The Life and Death of Proteins 2013
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Syllabus 

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The purpose of this course is two-fold. 

Conceptually, we will explore the problem of protein folding and protein aggregation, starting at the molecular level to look at the way chaperones help proteins fold and remain in their native state, proceeding to the cellular network of protein folding quality control pathways and stress responses, and going all the way up to aging organisms and specific tissues that are affected by the proteotoxic stress of protein misfolding and aggregation. We will cover research topics in the field of folding and aggregation that span several model systems and emerging methodologies. 

In addition, from the practical side of things, the purpose of this course is to develop our ability to process and integrate scientific literature, and to communicate ideas to others in scientific writing and scientific talks. 

Announcements

We will be meeting in the seminar room 1-402 (note that this is different from the room specified in the course listing). 

Course organization

The course will be organized as an advanced seminar for graduate students and 3rd year undergraduates, though other students are more than welcome to apply. We will meet once a week for two hours. 

Every week I will assign one "mandatory" review article, one "mandatory" research article for presentation and discussion,  and another research article that will be presented in 15min by another student. Additional useful articles will be posted as well. I will upload the PDFs of the articles to this site. There will be a weekly assignment to write an "abstract" summarizing the research article assigned for the discussion. There will be a strict 250 word limit for the abstract, which will be graded for being succinct, accurate, and thorough. 

During the first 30min I will give a brief "chalk" presentation about the discussion topic for the following week. During the second 30min two students (different students every week) will give a short power-point presentation about the article assigned for discussion. For the remaining time, we will discuss the article together.

The final project will be a 15 min presentation on a sub-field of your choice with a proposed experimental program. We encourage students to be creative in choosing the topic. There will be an option of a power-point presentation or a "chalk-talk." Due to the number of students in the course, the talks will have to be short (15min). Therefore, we will also ask the students to submit a 1-2 page summary/proposal to go along with the presentation. 

The grade will consist of:
15% 1st presentation
35% 2nd presentation and proposal
40% average of weekly abstracts (the lowest grade will be dropped)
10% participation in weekly discussions

Weekly Schedule

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February 20
Introduction to Seminar course


Protein Folding - The Life and Death of Proteins        
       Exiting the Ribosome
       Co-translational folding and degradation
       Chaperones and Chaperonins
       Folding in compartments (Cytosol and ER)
       Proteasomal Degradation 
       Misfolding and Marginal stability


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February 27 - Dan
Protein Folding Quality Control - To Fold or to Destroy        
        Chaperone systems and Quality Control
        Small Heat Shock Proteins
        Ubiquitination of misfolded proteins
        Quality Control in Compartments (Cytosol, Nucleus, ER)

Assigned Paper for Summary and Discussion (Gardner, Cell)
Assigned Paper for Presentation (McClellan et al, 2005)
                                                                        
                                                                         Review (Wolf)
                                                                        
                                                                         Suggested Paper (England Structure)
                                                                         Suggested Review (Gierash)
                                                                         Suggested Review (Chaperones, Foldases)

                                                                        

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March 6 - Dana
Intrinsically Disordered Proteins (IDPs) and Quality Control
Intrinsic unfolding and its role in protein interaction
Degradation processes of natively unfolded proteins
Role of protein flexibility in chaperone function
Evolution of IDPs
Assigned Paper for Summary and Discussion (Gardner, Mol Cell)
Assigned Paper for Presentation (Hsp33 chaperone)

                                                                                      Suggested Review (Jakob & Bardwell,2012)
                                                                                      Suggested Review (Mittag, 2009)




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March 13 - Dan
Protein Aggregation - Sticking Together        
        All proteins can aggregate, but what does that mean?
        Phase separation
        Amyloids
        Inclusions
        Yeast Prions
  Review (Brangwynne)
  Review (Alberti)
  Assigned Paper for Summary and Discussion
  Assigned Paper for Presentation
                                                                         Suggested Paper (Treusch and Lindquist)
                                                                       
                                                                       
                                                                       


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March 20 - Dan
Spatial Organization of the Cytosol and its Functions
Review (Ungermann)
Review (Alberti)        
Review (Tyedmers)
Review (David)
         
        Assigned Paper for Presentation  (Tyedmers 2010)
        Assigned Paper for Summary and Discussion (Oling and Nystrom, 2014)
        
                                                                            Suggested Paper (Weisberg et al., 2012)
                                                                            Suggested Paper (Hudder et al, 2003)
                                                                            Suggested Paper (Dobson)
                                                                            Review (Gierash) 
                                                                            Review (Zhou) 


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March 27 - Dan
Spatial Quality Control - If You Can't Beat Them, Get Rid of Them
Review (Nystrom)
Review (Barral)       
Assigned Paper for Summary and Discussion
Assigned paper for Presentation

Suggested Paper (Nystrom)
Suggested Paper (Nystrom)
                                                                    Suggested Paper (Spokoini et al., 2013)

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May 1- Dana
Chaperones and Evolution
        Assigned paper for presentation (Tokuri & Tawfik, GroEL expression and enzyme evolution )
        Assigned paper for Summary and Discussion (Jaroz & Lindquist, Hsp90 and genetic variation)
        Review about chaperone buffering
       
Review about directed evolution of enzymes

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May 8 - Dana
Redox and Aging - Aging Old Question 
   
        Assigned paper for summary and discussion - Role of oxidation in development
        Assigned paper for presentation only - Sensing in-vivo ROS levels
        Paradox of Insulin signaling Review
        suggested review

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May 15 - Dan
Neurodegenerative Disease Models
Assigned Paper for Discussion and Summary
Assigned Paper for Presentation Only
Additional Paper
Revevant Review (Bennett)
Review Lansbury and Lashuel

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May 22 - Dana
Proteostasis - Dynamic Protein Structure 
         Paper for Summary and Discussion
         Paper for Presentation
         Review (Shamir and Kaganovich)
         Recommended Paper
         Recommended paper
         Review (Ankerhold)        
         Review (Lippincott-Shwartz)

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May 29 June 12, 19
Student presentations

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