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 Protein Folding, Misfolding and Human Disease  posted by  duggu   on 12/8/2007  Add Courseware to favorites Add To Favorites  
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Kosinski-Collins, Melissa, 7.343 Protein Folding, Misfolding and Human Disease, Fall 2004. (Massachusetts Institute of Technology: MIT OpenCourseWare), (Accessed 07 Jul, 2010). License: Creative Commons BY-NC-SA

A schematic diagram of folding in the protein Subtilisin BPN'.
The enzyme Subtilisin BPN' has been the subject of numerous protein engineering studies. This monomeric protein has a substantial kinetic barrier to folding and unfolding, and is of great industrial importance. (Image courtesy of Dr. Philip Bryan, University of Maryland Biotechnology Institute. Used with permission.)

Course Highlights

This course features a full bibliography in the readings section.

Course Description

This course is one of many Advanced Undergraduate Seminars offered by the Biology Department at MIT. These seminars are tailored for students with an interest in using primary research literature to discuss and learn about current biological research in a highly interactive setting. The instructor for this course, Dr. Kosinski-Collins, is a member of the HHMI Education Group.

Maintenance of the complex three-dimensional structure adopted by a protein in the cell is vital for function. Oftentimes, as a consequence of environmental stress, genetic mutation, and/or infection, the folded structure of a protein gets altered and multiple proteins stick and fall out of solution in a process known as aggregation. In many protein aggregation diseases, incorrectly folded proteins self-associate, forming fiber-like aggregates that cause brain cell death and dementia. In this course, the molecular and biochemical basis of the prion diseases, which include bovine spongiform encephalopathy (mad cow disease), Creutzfedt-Jakob disease and kuru will be examined. Also discussed are other classes of misfolding diseases such as Alzheimer's disease and Huntington's disease. The proteins involved in all of these disorders and how the proteins' three dimensional structures change during the course of these afflictions is covered as well as why prions from certain species cannot infect animals from other species based on protein sequence and structure. The course will then address possible detection methods and therapies that are under development to treat some of the protein aggregation diseases.


Course Format

During the typical class session, we will analyze two papers in a discussion-based format. Everyone should read both papers before class, and each student should be prepared to answer questions. At the beginning of each class, we will have a question and answer period in which the instructor will respond to any specific questions that the students may have thought of while reading the articles. Immediately following, one or two students will present a brief summary of techniques essential to the topic of the papers. Students may volunteer to present the technique(s) of interest during the week prior to the discussion. We will spend the remainder of the class discussing the data presented in the article by analyzing each figure and resulting conclusions. Each class will conclude with a brief outline of the following week's class introduced by the instructor.

Note: The review and response articles have been included as supplemental material. I encourage you to read them to get a feel for the topic background, but they are not required reading and we will not discuss them directly.


Because this course has no graded exams, students are expected to attend every class meeting. The major focus will be on discussion and interpretation of scientific papers, so student attendance and participation is essential. Other than week 1, there will be no formal lectures and students should come to class prepared to participate in a discussion of the assigned papers. Missing a class should occur only in extreme circumstances. If a student knows he/she must miss a class, he/she must contact the instructor in advance and receive permission for the absence. Students who have been allowed an excused absence will be asked to complete a written assignment concerning the papers discussed during the missed class session.


As the goal of this course is to familiarize students with the reading and critical evaluation of the primary literature in the protein folding field, students are expected to have completed 7.03 (Genetics), 7.05 (Biochemistry), 7.06 (Cell Biology) or 7.08 (Molecular Biology). We will be dealing with several topics related to protein structure and design, and so a reasonable knowledge of introductory chemistry or biochemistry will be helpful.


There are no formal exams. The class has a pass/fail grading system.


In addition to the weekly reading assignments, there will be three one to two page written assignments and an oral presentation coinciding with the first written assignment.




1 Background of Protein Misfolding and Disease  
2 Origins of the Protein-only Hypothesis of Prions  
3 Controversial Evidence against the Virus-hypothesis of Prion  
4 Pathology of the Transmissible Spongiform Encephalopathies  
5 Structure of the Prion Protein  
6 The Prion Species Barrier Assignment 2 due
7 Detection of Prion Diseases in Humans and Animals  
8 Alzheimer's Disease  
9 Transmission Electron Microscopy: Field trip to TEM facility  
10 Oligomeric Ring Structures in Alzheimer's and Parkinson's Disease  
11 Parkinson's Disease and α-synuclein  
12 Polyglutamine repeats in Kennedy's and Huntington's Diseases  
13 Senile Systematic Amyloidosis and Inflammation Assignment 3 proposal due   Tell A Friend