Course Meeting Times
Lectures: 1 session / week, 2 hours / session
There are no absolute prerequisites, but some knowledge of genetics, biochemistry and cell biology is expected. Ideally, candidates have successfully taken at least one of the following classes:
7.05 General Biochemistry
Parasites require a hospitable organism to reproduce and spread and have evolved multiple strategies to subvert their hosts. Parasites scavenge nutrients directly from host cells, evade the host immune system and even modify host behavior to increase their transmission. This course will explore the strategies used by a ubiquitous and harmful class of parasites to hijack the biology of their host cells. We will discuss pathogens such as Plasmodium and Toxoplasma, responsible for some of the deadliest and most ubiquitous infectious diseases on the planet.
Malaria is caused by several Plasmodium species and causes more than half a million deaths a year, mostly of children under five. After being transmitted through a mosquito bite, Plasmodium invades the liver and red blood cells. One of the most important manifestations of malaria is the modification of red blood cells by the parasite, causing them to stick to the walls of small blood vessels. Vessel blockage in the brain causes cerebral malaria, the most fatal form of the disease. As a pathogen of humans for the past 100,000 years, Plasmodium has evolved elegant strategies to survive and ensure its transmission, for example by hiding from the human immune system; it has been suggested that Plasmodium alters the behavior of infected mosquitos by making them more likely to seek hosts and to feed more often, thereby increasing the transmission of the parasite.
Toxoplasma gondii might be the world's most successful pathogen, infecting up to half the human population. Although its sexual cycle only takes place within cats, Toxoplasma is able to survive within almost all warm-blooded animals. In humans, Toxoplasma gondii causes a chronic and asymptomatic infection in immuno-competent subjects. However, in immuno-compromised patients, Toxoplasma can cause fatal brain inflammation. Toxoplasma infection of otherwise healthy pregnant women can cause miscarriage, and Toxoplasma variants are a leading cause of eye disease in otherwise healthy people in South America. Intriguingly, chronic Toxoplasma infection has been linked to interesting behavioral alterations; for example, infected mice lose their fear of cats, increasing their chance of being eaten and so completing the parasite's life cycle. In humans, Toxoplasma infection has been linked to risk-taking behavior and might be involved in schizophrenia.
By exploring how these pathogens invade a host cell and replicate while evading the immune system, students will gain a broad understanding of basic cell biology, biochemistry and immunology, as well as learn techniques commonly used in cell biology. A major goal of the course is to teach students to critically analyze the primary research literature. Students will be challenged to think creatively and flexibly to understand, critique, interpret, and design scientific experiments in the field of host-pathogen interactions. This course will include a field trip to an academic laboratory focused on host-pathogen interactions, where students will learn about the use of several cutting-edge techniques for the study of the biology of Toxoplasma and the impact that these tools are having on the field of molecular parasitology.
During each class, two scientific manuscripts will be assigned as required reading for the next class. Students should analyze the papers in preparation for each class and use the following guiding questions which will provide the basis for discussion during each session:
- What are the key experiment and control of the paper?
- Are the data presented sufficiently convincing to support the final conclusion? If not, what other experiments will be needed to support the 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 data (e.g. bad western blots, statistical flaws, no quantifications etc.)
- What related questions remain unanswered by this study? What new questions have arisen given the authors' conclusions?
- 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 research 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 the following week's topic. One or both instructors will provide an introduction to the problem and methods to be addressed by the next session's papers and offer some background about the state of the field at the time the paper was published.
This course will be graded Pass / Fail. To pass this course, students are expected to:
- attend all class sessions and participate actively (and fulfill all make-up assignments) and
- complete both the oral and written assignments.
|WEEK #||TOPICS||KEY DATES|
|2||Alien invasion: How Toxoplasma secretly enters host cells|
|3||Make yourself at home: Intracellular survival in the parasitophorous vacuole|
|4||How parasites transport proteins and nutrients across membranes|
|5||The transforming parasite: How Theileria modifies its host cell in order to replicate|
|6||(Don't) Divide and Conquer: How Toxoplasma pauses the host cell cycle||Midterm Written Assignment due|
|7||Field trip||Field trip to the Lourido Lab, at the Whitehead Institute|
|8||Jamming communications: Strategies to thwart innate immunity|
|9||The fatal consequences of hide and seek: How changes in Plasmodium's surface increases disease severity|
|10||Malarial mind control–Plasmodium increases transmission by modifying mosquito behavior|
|11||Of mice, rats, cats, leopards and chimpanzees|
|12||Oral presentations||Oral Presentations due|