Syllabus

Course Meeting Times

Lectures: 1 session / week, 2 hours / session

Prerequisites

There are no formal prerequisites, but some knowledge of genetics, biochemistry and cell biology is expected. Ideally, candidates have successfully taken at least one of the following classes:

7.03 Genetics

7.05 General Biochemistry

7.06 Cell Biology

7.28 Molecular Biology

Course Description

In humans, the mucosal epithelia that line the gastrointestinal, urogenital and respiratory tracts are important routes of entry for bacterial pathogen invasion. At the same time, mucosal surfaces are colonized by many harmless bacteria, the so-called commensals or microbiota. Not only are these commensals well-tolerated and non-pathogenic, but also they are in fact essential for diverse body functions, such as nutrient absorption and synthesis of vitamins (biotin and vitamin K). Interestingly, most of us do not develop a strong immune response against commensals (or, similarly, against the food we eat every day). This striking specificity of recognition reflects the tight regulation of the immune system at mucosal surfaces to maintain a balance between tolerogenic and effector immune responses.

In this course, we will examine how the immune system acts to destroy pathogenic invaders while tolerating colonization by necessary commensal bacteria. As a counterpoint, we will also explore sophisticated strategies that help some bacteria evade our immune system. Did you know that the intestinal mucosa is considered to be always "physiologically inflamed," because of its daily exposure to, and activation by, foreign antigens? Or that sub-populations of certain pathogenic bacteria employ suicidal strategies to promote surface colonization? These and many more interesting aspects of host-commensal / hostpathogen interactions will be introduced and analyzed.

We will critically review the primary research literature and systematically discuss the experimental data, leading us to either concur with or challenge published analyses and conclusions. We shall ask questions such as: Are there additional controls that are essential to validate the interpretations? Are there further experiments that would have strengthened the conclusions? What experiment would you do next if this study were your responsibility? Such questions will help direct our discussions beyond the confines of the research paper being discussed. We hope that this course will excite students to join the next generation of scientists who explore the intersection of host-pathogen interactions and immunology.

Format

In preparation for each class, two scientific manuscripts will be assigned as required reading during the class of the previous week. We encourage students to analyze the papers in preparation for each class having the following guiding questions in mind that will be used in the discussion during each class:

• What are the key experiment and the key control?
• Are the data as presented sufficiently convincing to support the final conclusion?
• Is there a particular experiment missing that would have strengthened the findings?
• Are there additional controls that would have increased the robustness of the data?
• Is the interpretation of the experimental data clear and rational?
• Are there any questionable figures or tables (e.g. bad western blots, statistical flaws, etc.)?
• Is there anything that you could not understand (methodology, etc.)?

The major aim of the course is to help students develop a strong ability to critically read and discuss a paper. The class sessions will focus on discussing the results and the methods used to respond to the questions the authors wanted to address. We will critically analyze the articles using the guiding questions listed above. The final 10–15 minutes will be dedicated to next week's topic. One or both of us will provide an introduction to the problem to be addressed by next session's papers and offer some background about the state of the field at the time the paper was published.

Grading

The class is graded on a pass / fail basis. To pass this course, students are expected to:

1. Attend all class sessions and participate actively (or fulfill all make-up assignments) and
2. complete both the oral and written assignments.

Calendar