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Weekly Pre-class Assignments
To ensure everyone is prepared for class discussions, each student will send the instructor brief written answers to a few basic questions about each article. Each assignment will be submitted the night before class. The format will be as follows, with answers to be brief (1–2 sentences each):
- What was the main gap in knowledge this article was trying to address?
- What was the main experiment (or experiments) that answered this question?
- What was the most important control in the main experiment?
- What is the major takeaway finding of the article?
- Name one outstanding question from the article you would try to follow up on if you were the researcher?
- Optional—is there anything unclear (or interesting!) from the article you specifically want to discuss during class?
Midterm Assignment, Due Week 6
Students will be provided an unpublished primary research paper with the title and abstract missing in week 4. Students should propose 1) a title, 2) an abstract, and 3) a graphical abstract (see below). The instructor will provide feedback about this assignment to help you identify areas in which you are excelling and areas that need improvement.
- Title: Think about what is the one-sentence takeaway from the research. The title should be about 1 line of text, 1 sentence.
- Abstract: The abstract should be 200–350 words in length (about 8–12 sentences). Think about answering the following questions:
- What is the main subject of the article?
- What was the major question/gap in knowledge?
- What were the main methods used and the major finding of the paper? (Focus on the main experiment or experiments, distinguishing which data are critical and which play a supporting role.)
- How does this paper impact the overall field?
- Formatting requirements: Times New Roman, 12 point font, 1 inch margins, double-spaced.
- Graphical abstract: Put the article into pictures! Graphical abstracts are becoming a popular way to summarize articles and engage readers.
- You may hand-draw the figure(s), use clip art from Google Images, etc. (The key for this class is not artistic talent but rather the ability to convey a conceptual understanding of the article.)
- The content of the graphical abstract corresponds to that of the written abstract—main question, main method, and main takeaway. There can be limited text, but the major takeaway should be conveyed through images.
- See some examples: https://www.cell.com/pb/assets/raw/shared/figureguidelines/GA_guide.pdf
Final Assignment, Due Week 13
By the end of the semester, we will have been exposed to many different organisms and diseases through scientific papers. In your final assignment, you will pick a primary journal article written in the last 5 years. This paper can address a topic we haven’t covered or follow up on a topic you found really interesting during the semester. (The topic should be broadly within the field of infectious diseases.)
During the last session of the course, each student will give a 15-minute oral presentation about their chosen topic/article. Critically analyzing the experimental design and interpretation of the data will be the primary focus of this assignment, and the majority of your slides should focus on these issues, not on introductory or summary material. The presentation should be 12 slides. The presentation will be followed by a discussion wherein the presenter will answer questions from other students and the instructor. The presentation should provide 1)a brief introduction to the general topic surrounding the research and describe the contribution the research attempts to make towards this topic; 2) an overview of the key experiments and how they were controlled, key findings; and most importantly, 3) a critical evaluation of the work with an emphasis on whether or not the experimental results support the conclusions of the authors.
The presentation should be formatted as follows:
- A title slide featuring the manuscript name, authors, author affiliation, journal name, and date of publication.
- 2–3 slides introducing the topic and the research question.
- 4–5 slides featuring the key experiments, controls, and results (utilizing figures from the paper).
- 2–4 slides presenting a critique of the work, supported with techniques, controls, or alternative experiments that might enhance the findings of the paper. This is the most important aspect of the presentation.
Instructor Interview
Below, Dr. Lisa McLellan describes various aspects of how she taught 7.341 Microbes At War: The Mechanisms That Drive Infectious Diseases in the fall of 2022.
OCW: How did teaching this course as a postdoc at MIT influence your approach as an educator?
Lisa McLellan: Teaching the course reinforced the importance of fostering critical thinking and scientific literacy among students. Engaging undergraduates in the analysis and discussion of primary literature allowed them to develop these skills in a hands-on manner. Additionally, teaching at MIT exposed me to a diverse group of students with varying levels of background knowledge and expertise. This experience taught me the value of adapting teaching strategies to meet the needs of different learners and creating an inclusive learning environment. These lessons have proved invaluable in my current position at Purdue University Fort Wayne, where I continue to prioritize active learning, inclusive teaching strategies, and student engagement.
OCW: Each of the Advanced Undergraduate Seminars offered by the MIT Biology department explores a different topic, but the overall structure of the seminars is fairly standardized. What are your thoughts on developing a course within a pre-established format in this way?
Lisa McLellan: Developing a course within the structured format allowed me to blend innovation with established guidelines. While the seminars maintained a standardized framework, there was room for creativity in tailoring the content to the specific topic and in how I approached day-to-day operations in the classroom. As a new instructor, this balance allowed for me to innovate in the classroom while ensuring consistency with departmental expectations. It also challenged me to think critically about how to effectively engage students within a predefined structure, enhancing my ability to design courses that are both rigorous and engaging.
OCW: How did you go about selecting the readings for the course? Were you primarily concerned with choosing the most up-to-date papers? The most influential papers within the field? Or the ones that you thought would particularly lend themselves to analysis and discussion?
Lisa McLellan: Selecting readings for the course involved a combination of factors. As a graduate student at Washington University, I was blessed to be a teaching assistant for Dr. Petra Levin in an undergraduate journal club of infectious diseases. In this class, I was exposed to some of my favorite scientific papers of all time and used many of these papers as a springboard for discussion topics (huge thank you to Dr. Levin for her amazing mentorship!). After that, I prioritized influential papers within the field that provided foundational knowledge and sparked thought-provoking discussions. Additionally, I sought papers that would lend themselves well to analysis and interpretation, encouraging students to delve deeper into the scientific process and hone their critical thinking skills. Further, as the students themselves had just lived through a global pandemic, I tried to choose papers that highlighted some of the scientific concepts they were exposed to during the COVID-19 pandemic. This allowed both cutting-edge but also foundational knowledge to be woven into the course.
OCW: What are your thoughts on the pedagogical value of the field trip to Concerto Biosciences? What did your students get from that experience that they couldn’t get in the classroom?
Lisa McLellan: The field trip provided invaluable real-world exposure for students, allowing them to see how the research papers they read translated into the biomedical industry. By visiting a biotech company, students gained a deeper understanding of how scientific research translates into practical applications and the interdisciplinary nature of the biotech industry. Furthermore, interacting with professionals in the field allowed students to gain valuable career insights, witnessing firsthand a career they had not been exposed to. Overall, the field trip enriched the learning experience by providing perspectives and experiences that couldn’t be replicated in the classroom alone.
OCW: What would you like to share about teaching 7.341 that we haven’t yet addressed?
Lisa McLellan: One aspect of teaching 7.341 that I would like to highlight is the importance of fostering a collaborative and supportive learning environment. Encouraging active participation and respectful dialogue among students not only enhances their understanding of the material but also cultivates a sense of community and shared learning. Further, in this course, I implemented student-driven learning by allowing students to help guide some of the topics for discussion and analysis. This approach not only empowered students to take ownership of their education but also ensured that the course content resonated with their individual interests and career aspirations.
Moreover, I also took class time to explore and consider scientific controversies and ethical dilemmas within the field. This added depth to the discussions and encouraged students to grapple with the complexities of scientific research. By incorporating diverse perspectives and addressing ethical concerns, we challenged students to think critically about the implications of scientific advancements and to consider the broader societal impacts of their work. This approach not only enriched the learning experience but also fostered a deeper understanding of the responsibilities inherent in scientific inquiry.
Curriculum Information
Prerequisites
A background knowledge of genetics, biochemistry, and cell biology is expected, ideally including at least one of the following classes: 7.03 Genetics, 7.05 General Biochemistry, 7.06 Cell Biology, 7.08 Fundamentals of Chemical Biology, 7.21 Microbial Physiology, or 7.28 Molecular Biology.
Requirements Satisfied
Unrestricted elective credits
Offered
Advanced Undergraduate Seminars are offered nearly every semester and are on various topics. This was the first time this specific topic was offered.
Assessment and Grading
The course is graded as “pass” or “fail.” A passing grade is given to students who attend the class, participate in discussions, and complete both assignments in a satisfactory manner.
Student Information
Enrollment
Fewer than 10 students
Student Background
All students were either juniors or seniors, majoring either in Biology or in Chemistry and Biology.
How Student Time Was Spent
During an average week, students were expected to spend 6 hours on the course, roughly divided as follows:
Lectures
- Met once per week for 2 hours per session; 14 sessions total; mandatory attendance
- In the first part of each week’s class, students discussed and evaluated the papers that comprised the readings for the week.
- At the end of each class, the instructors gave a short introduction to the papers for the following week.
Out of Class
- Each week, students read two papers from the primary research literature and critically evaluated these papers focusing on experimental design, control experiments, methods and interpretation of the data.
Each Lecture Summary is based on the corresponding Readings for that week.
Week | Topics | Lecture Summaries |
---|---|---|
1 | Welcome to the “Battlefield”— Introduction to Host-Pathogen Interactions and How to Effectively Read Journal Articles | In this introductory week, we will introduce ourselves and discuss the course logistics. We will discuss key concepts and definitions related to host-pathogen interactions. We will also examine approaches for searching, cataloging, and reading primary literature articles. The goal when reading journal articles is to be able to 1) efficiently find the main points, methods, and conclusions and 2) critically analyze the main conclusion. We will discuss strategies to accomplish these goals. |
2 | Identify the Enemy—Koch’s Postulates |
Koch’s postulates are a set of 4 criteria used to establish whether an organism is the cause of a specific disease. To fulfill Koch’s postulates, the microbe (1) must be found in diseased but not healthy individuals, (2) must be cultured from the diseased individual, (3) must recapitulate the disease when a healthy individual is inoculated with the cultured microorganism, and (4) must be re-isolated from the inoculated, diseased individual and matched to the original microorganism. The first paper is one of the most direct examples fulfilling Koch’s postulates, showing that the bacterium Campylobacter (now known as H. pylori) causes stomach ulcers. This paper resulted in one of the authors winning a Nobel prize! The second paper focuses on molecular analogs of Koch’s postulates—how we know a specific protein (or virulence factor) is involved in disease progression. |
3 | The World’s Deadliest Infectious Disease—Tuberculosis |
Tuberculosis caused by the bacterium Mycobacterium tuberculosis has shaped human health and history. Tuberculosis remains one of the world’s deadliest infections, infecting one-fourth of the world’s population and causing 1.4 million deaths per year. One of the first challenges in controlling an infectious disease is understanding the mechanism of transmission (air, object contact, or fecal/oral). Think back to the first months of COVID-19—why did we need to wear masks and was it necessary to wipe down groceries with disinfectant? With the first paper, which describes how we know that tuberculosis is air-transmittable, we will explore how scientists address questions of transmission. The second paper uses a model organism, the non-infectious bacterium Mycobacterium smegmatis, to study Mycobacterium bacterial division and considers how the mechanism of cell division impacts the use of antibiotics, a major line of defense against bacterial infections. |
4 | On the Front Lines—How Bacteria Can Stake Their Claim on the Battlefield |
To cause an infection, a pathogen must actually stick around and survive in a location. If the pathogen can’t survive in a niche, it can’t cause infection. To demonstrate this concept, we will focus on urinary tract infections, caused by the bacterium E. coli and affecting 50% of women throughout their lifespan. E. coli use sticky protein fibers, called adhesins, to bind sugars on the bladder surface and avoid being eliminated from the bladder during urination. Type 1 pili are a type of E. coli adhesin critical for E. coli survival in the bladder. The first paper shows the identification of the receptor for type 1 pili in the bladder. The second paper shows how E. coli uses this same adhesin in a different niche, the human gut, and how a medicinal sugar, called a mannoside, can target this interaction to eliminate the bacteria from the host. Note: Sometimes journals provide summary articles or commentaries about published articles. Such summaries can offer fun ways to see other scientist’s perspectives about the articles. If you are interested, see if you can find a few such commentaries about the second article! |
5 | Not All Microbes Are Bad—Field Trip Preparation |
We have been primarily focused on microbes that cause diseases. However, only a minority of microbes are disease-causing in humans. In fact, the human microbiome does a lot to protect us against diseases. For this reason, many companies are using microbes to improve health. Dove soap even advertises that it works to protect your microbiome! This week, we will shift to thinking about positive microbes and microbial technologies in relation to our field trip. We will read two papers by the founders of the company Concerto Biosciences. The first paper looks at how bacteria often interact in microbial communities in a positive manner to promote growth of the community. The second paper focuses on a new technology, Combinatorial Arrayed Reactions for Multiplexed Evaluation of Nucleic Acids (CARMEN). CARMEN is a technology that is able to rapidly examine large quantities of patient samples simultaneously for multiple different types of pathogens. (In the paper, the authors are able to detect 169 different human-associated viruses from patient samples!) |
6 |
Field Trip!!! Concerto Biosciences Written Assignment Due |
This week we will visit a local start-up company, Concerto Biosciences. Many of their scientists trained here at MIT! Read more about their mission. We will talk about both science and scientific careers, and your only prep for this week is to look at the company website and think about any questions you might have about their company! Please dress appropriately for walking around a laboratory—e.g., wear closed-toe shoes this week. Additional instructions for the field trip (traveling to Concerto, clothing, etc.) will be provided prior to class. |
7 | Preprint Week—and the Mysterious Hepatitis Outbreak |
We have been working to hone our critical reading skills. Now is your chance to put your skills to the test. This week we will be reading preprints! As noted in our last session, preprints offer a way for scientists to post their findings before they are submitted to journals for peer review. Doing so allows authors to release new findings rapidly and to receive feedback from the broad scientific community prior to publication. However, use of preprints can go awry— since the information hasn’t undergone peer review, you need to be critical about what preprints are claiming, as it might be completely wrong! Just remember, just like any information taken from non-validated sources, preprint information might be wrong. Two common preprint servers in health sciences are BioRxiv and MedRxiv. This week, we will look at two papers from MedRxiv. Currently, there is an outbreak of hepatitis (liver inflammation) in children. This outbreak has no apparent cause! (Google “Hepatitis in children 2022” to see the latest news on this topic.) Normally hepatitis is caused by a number of known hepatitis viruses (A-E) but these were not detected in the affected children. The first paper suggests that a different virus called adeno-associated virus 2, or AAV-2, might be associated with the hepatitis outbreak. This virus commonly infects children but has never been linked to human disease. Interestingly, as AAV2 typically requires a coinfecting “helper” virus to replicate, this paper looks at an additional herpesvirus that might also be involved. The second paper identifies a specific genotype of MHC class II molecule—class II HLA allele HLA-DRB1*04:01—in infected children. MHC molecules allow antigens in foreign bodies such as viruses to be presented by antigen-presenting cells (such as dendritic cells, macrophages, and epithelial cells) to professional killing cells (such as T cells), thereby triggering the immune system to respond to the infection. |
8 | Illness Is Sweeping through the Ranks—Norovirus (Winter Vomiting Bug) |
Norovirus is highly contagious and causes vomiting and diarrhea. Norovirus has been known to temporarily shut down universities and cruise ships. This week we will re-example the concept of receptors that we explored during our consideration of urinary tract infections. The first paper uses a CRISPR screen to identify the receptor for murine norovirus. CRISPR screening is a modern technique that is changing the way we do science both in academic and commercial labs. The second paper explores how model organisms sometimes do not tell the whole story. This week, we will discuss the benefits of and drawbacks to using model organisms. We will also consider different types of genetic screens, what types of information such screens provide, and what limitations genetic screens have. |
9 | Biological Sex, Pregnancy, and Infectious Diseases—Malaria |
Malaria is caused by a human parasite, Plasmodium. Plasmodium is thought to have contributed to the fall of the Roman Empire. Malaria continues to cause millions of infections a year, most often in tropical climates. Malaria can be particularly dangerous to pregnant women and the developing fetus. The first paper describes how parity (the number of pregnancies a woman has had) impacts pregnancy-associated malaria through the production of specific antibodies. We will think about how studies are controlled and how age and biological sex are a part of this discussion. The second paper discusses co-infection of HIV and malaria, a common issue in Africa. We will consider how the first paper suggests a potential good vaccine target for pregnancy-associated malaria and how the second paper impacts our understanding of malaria treatment options |
10 |
Friendly Fire—How the Immune System Can Go Awry, and a Tick Bite Can Lead to Allergic Reactions to Meat Final Presentation Topic Due |
The immune system is meant to protect us and does a lot of work to keep us healthy. However, sometimes the immune system has unhelpful overreactions, such as in anaphylactic shock. Today we will discuss two stories about the human immune system that proved to be surprisingly interconnected. The monoclonal antibody cetuximab was in clinical trials for treatment of colon cancer, but patients were developing anaphylactic reactions to the antibody. At the same time, a group of outdoorsy patients were developing an anaphylactic reaction to meat. It turned out that the allergic reactions to cetuximab and meat both involved a hypersensitivity reaction to a galactose-alpha-1,3-galactose (alpha-gal). Alpha-gal is a sugar present on non-primate red blood cells, and all non-immunocompromised humans have antibodies against this sugar moiety. The presence of alpha-gal antibodies in humans is a barrier against using non-primate organs for organ transplants! Paper one examines alpha-gal hypersensitivity reactions though the lens of cetuximab, and paper two tackles alpha-gal hypersensitivity reactions through the lens of the red meat allergy. Note: A fun (optional) podcast to supplement today’s class: “Alpha Gal,” Radiolab podcast, Oct. 27, 2016. Produced by Annie McEwen & Matt Kielty with reporting help from Latif Nasser. WNYC Studios. |
11 | A Battle You Have Been a Part of—The Global Fight Against COVID-19 |
COVID-19, caused by the SARS-CoV-2 virus, doesn’t need much introduction—COVID-19 a global pandemic we have all been living through. This week we will discuss two interesting features of COVID-19—the loss of taste/smell and the varied severity of the reactions people have to the virus. The first paper discusses how downregulation of olfactory receptors might be a mechanism by which SARS-CoV-2 causes loss of taste and smell. The second paper discusses how patients who develop neutralizing autoantibodies against interferon-ω appear to develop severe disease. We will also talk about the pros and cons of scientific research moving so quickly—why does the second paper have 107 authors? Why have more than 250 COVID-19 papers been retracted? And why does the BioRxiv preprint server (which makes papers publicly available prior to peer review) have a special note about COVID articles: “BioRxiv posts many COVID-19-related papers. A reminder: they have not been formally peer-reviewed and should not guide health-related behavior or be reported in the press as conclusive.”? |
12 | What Is Your Favorite (or Least Favorite) Microbe? | You have worked hard to make it to this point in the class. Is there a topic (microbe, host defense, etc.) that you can’t get enough of? A favorite disease we have yet to explore? This week you get to choose! (We will vote during week 10 for a topic to be discussed this week.) Some potential topics are: Do vaccines cause autism (note: they do not—but we can discuss where this incorrect information comes from)? Do this year’s Nobel Prizes in Physiology or Medicine or in Chemistry relate to infectious diseases? Do antidepressants cause weight gain? (One does, and it works through the microbiome!) What are poop pills, and do they work? What are people doing about multidrug-resistant pathogens? How do some viruses cause cancer? These are just some options to consider—the world of microbes is all yours! |
13 | The Final Battle—Oral Presentations | Our concluding course meeting is focused on the final oral presentations, as described in the Assignments section. In addition, we will consider what we have learned about the field of host-pathogen interactions and its future directions. Lastly, students will complete course evaluations and provide feedback about the course. |
See the Lecture Summaries to read about the discussions that took place around each week’s readings.
Week | Topics | Readings |
---|---|---|
1 | Welcome to the “Battlefield”—Introduction to Host-Pathogen Interactions and How to Effectively Read Journal Articles | [No Readings] |
2 | Identify the Enemy—Koch’s Postulates |
Marshall B.J., Armstrong J.A., McGechie D.B., et al. Attempt to fulfill Koch’s postulates for pyloric Campylobacter. Med. J. Aust. 1985. 142 (8) : 436–9. doi: 10.5694/j.1326-5377.1985.tb113443.x. PMID: 3982345. Ohnishi N., Yuasa H., Tanaka S., et al. Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc. Natl. Acad. Sci. U S A. 2008. 105 (3) : 1003–8. doi: 10.1073/pnas.0711183105. Epub 2008 Jan 11. PMID: 18192401; PMCID: PMC2242726. |
3 | The World’s Deadliest Infectious Disease—Tuberculosis |
Riley R.L., Mills C.C., Nyka W., et al. Aerial dissemination of pulmonary tuberculosis. A two-year study of contagion in a tuberculosis ward. 1959. Am. J. Epidemiol. 1995, 142 (1) : 3–14. doi: 10.1093/oxfordjournals.aje.a117542. PMID: 7785671. Baranowski C., Welsh M.A., Sham L.T., et al. Maturing Mycobacterium smegmatis peptidoglycan requires non-canonical crosslinks to maintain shape. Elife. 2018. 7:e37516. doi: 10.7554/eLife.37516. PMID: 30324906; PMCID: PMC6231781. |
4 | On the Front Lines—How Bacteria Can Stake Their Claim on the Battlefield |
Zhou G., Mo W.J., Sebbel P., et al. Uroplakin Ia is the urothelial receptor for uropathogenic Escherichia coli: evidence from in vitro FimH binding. J. Cell. Sci. 2001. 114 (Pt 22) : 4095–103. doi: 10.1242/jcs.114.22.4095. PMID: 11739641. Spaulding C.N., Klein R.D., Ruer S., et al. Selective depletion of uropathogenic E. coli from the gut by a FimH antagonist. Nature. 2017. 546 (7659) : 528–532. doi: 10.1038/nature22972. Epub 2017 Jun 14. PMID: 28614296; PMCID: PMC5654549. |
5 | Not All Microbes Are Bad —Field Trip Preparation |
Kehe, J., Ortiz, A., Kulesa, A., et al. Positive interactions are common among culturable bacteria. Sci. Adv., 7 (45), eabi7159.PMCID: PMC8570599, DOI: 10.1126/sciadv.abi7159 Ackerman, C.M., Myhrvold, C., Thakku, S.G., et al. Massively multiplexed nucleic acid detection with Cas13. Nature, 582 (7811), 277–282. PMCID: PMC7332423, DOI: 10.1038/s41586-020-2279-8 |
6 |
Field Trip!!! Concerto Biosciences Written Assignment Due |
[No Readings] |
7 | Preprint Week—and the Mysterious Hepatitis Outbreak |
Morfopoulou S., Buddle S., Torres Montaguth O., et al. Genomic investigations of acute hepatitis of unknown aetiology in children. Nature. 2023. 617 : 564–73. doi: 10.1038/s41586-023-06003-w. Ho A., Orton R., Tayler R., et al. Adeno-associated virus 2 infection in children with non-A-E hepatitis. Nature. 2023. 617 : 555-63. doi: 10.1038/s41586-023-05948-2. |
8 | Illness Is Sweeping through the Ranks—Norovirus (Winter Vomiting Bug) |
Orchard R.C., Wilen C.B., Doench J.G., et al. Discovery of a proteinaceous cellular receptor for a norovirus. Science. 2016. 353 (6302) : 933–6. doi: 10.1126/science.aaf1220. Epub 2016 Aug 18. PMID: 27540007; PMCID: PMC5484048. Graziano V.R., Walker F.C., Kennedy E.A., et al. CD300lf is the primary physiologic receptor of murine norovirus but not human norovirus. PLoS Pathog. 2020. 16 (4) : e1008242. doi: 10.1371/journal.ppat.1008242. PMID: 32251490; PMCID: PMC7162533. |
9 | Biological Sex, Pregnancy, and Infectious Diseases—Malaria |
Salanti A., Dahlbäck M., Turner L., et al. Evidence for the involvement of VAR2CSA in pregnancy-associated malaria. J. Exp. Med. 2004. 200 (9) : 1197–203. doi: 10.1084/jem.20041579. PMID: 15520249; PMCID: PMC2211857. Keen J., Serghides L., Ayi K., et al. HIV impairs opsonic phagocytic clearance of pregnancy-associated malaria parasites. PLoS Med. 2007. 4 (5) : e181. doi: 10.1371/journal.pmed.0040181. PMID: 17535103; PMCID: PMC1880852. |
10 |
Friendly Fire–How the Immune System Can Go Awry, and a Tick Bite Can Lead to Allergic Reactions to Meat Final Presentation Topic Due |
Chung C.H., Mirakhur B., Chan E., et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N. Engl. J. Med. 2008. 358 (11) : 1109–17. doi: 10.1056/NEJMoa074943. PMID: 18337601; PMCID: PMC2361129. Commins S.P., Satinover S.M., Hosen J., et al. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-alpha-1,3-galactose. J. Allergy Clin. Immunol. 2009. 123 (2) : 426–33. doi: 10.1016/j.jaci.2008.10.052. Epub 2008 Dec 13. PMID: 19070355; PMCID: PMC3324851. |
11 | A Battle You Have Been a Part of—The Global Fight Against COVID-19 |
Zazhytska M., Kodra A., Hoagland D.A., et al. Non-cell-autonomous disruption of nuclear architecture as a potential cause of COVID-19-induced anosmia. Cell. 2022. 185 (6) : 1052–1064.e12. doi: 10.1016/j.cell.2022.01.024. Epub 2022 Feb 2. PMID: 35180380; PMCID: PMC8808699. Bastard P., Rosen L.B., Zhang Q., et al. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020. 370 (6515) : eabd4585. doi: 10.1126/science.abd4585. Epub 2020 Sep 24. PMID: 32972996; PMCID: PMC7857397. |
12 | What is Your Favorite (or Least Favorite) Microbe? | [No Readings] |
13 | The Final Battle—Oral Presentations | [No Readings] |
Basic Intro to Host-Pathogen Interactions
Definitions
- Host
- An organism infected by a pathogen
- An organism with which a microorganism is associated
- Reminder: this can be a human, animal, plant, insect, etc.
- Normal flora/microbiome
- Microorganisms associated with healthy host
- Pathogen
- A microorganism capable of causing an abnormality or disease
- Pathogens in the most strict definition are thought of as microorganisms (viruses, bacteria, etc)—however, prions (misfolding proteins that can be transmitted, e.g. mad cow disease) are considered “pathogenic agents.” They contain many features of microbial pathogens but are not strictly pathogens themselves.
- Opportunist
- Can cause disease in a damaged host, rarely in a healthy host
- Nosocomial pathogen
- Infection acquired in a medical environment
- Colonization/Infection
- Microorganisms growing on the host
- Must be able to replicate and reach a critical mass, otherwise not considered colonization (transient passage does not count)
- Pathogenicity/Virulence
- Ability of an organism to cause disease
- Virulence factor—some gene product that helps an organism cause more damage, establish itself better within a host
- Innate immune system
- Nonspecific, first line of defense
- Neutrophils (Polymorphonuclear leukocytes, or PMNs) are often our first line of defense.
- Adaptive immune system
- Memory system, T cells, B cells
- Infectious disease
- Actions of microorganisms and the reaction of the host INTERACTING to damage the host and able to spread into another permissive host
- Consider yeast: Baker’s yeast will not infect a healthy host. However, there are many types of yeast. In cases of immunosuppression, exposure to the correct biological niche, and correct virulence factors, various types of yeast, and yeasts that are not normally infectious, will cause an infection.
Types of Pathogens
- Bacteria
- Bacteria are unicellular organisms belonging to the prokaryotic group where the organisms have few organelles and lack a true nucleus.
- Viral
- A virus is an infectious microbe consisting of a segment of nucleic acid (either DNA or RNA, either single- or double-stranded) surrounded by a protein coat. A virus cannot replicate alone; instead, it must infect cells and use components of the host cell to make copies of itself.
- Fungi
- Domain Eukarya. As eukaryotes, a typical fungal cell contains a true nucleus and many membrane-bound organelles.
- Multicellular or unicellular
- Parasite
- An organism that lives on or in a host organism and gets its food from or at the expense of its host.
- This is really an ecology term for a type of interaction; as such this is a broader group that is a little harder to define.
- No specific phylogenetic way to define a parasite.
- The ability to “be a parasite” has evolved many times in the tree of life.
- Parasitism: a form of symbiosis in which one organism (“the parasite”) benefits at the expense of another (“the host”).
- Some broader groups of parasites:
- Protozoa are microscopic, one-celled organisms that can be free-living or parasitic in nature.
- Helminths are large, multicellular organisms that are generally visible to the naked eye in their adult stages.
- Ectoparasites—e.g. ticks, lice
- An organism that lives on or in a host organism and gets its food from or at the expense of its host.
So What Is a Microbe? (from discussion in class and also when surveying other microbiologists)
- An organism that is microscopic (However, many consider tapeworms microbes.)
- Things microbiologists study (not a super helpful definition because microbiologists study microbes!)
- Unicellular organisms (Do viruses fit this? What about multicellular microbes or microbes that have a multicellular lifecycle?)
- All small things with genomes (What is small in this case? Is there a size cut-off?)
- Microbiome people do not classify viruses as microbes because they are not living!
- For this class, we will use the following definition:
- A group of microscopic organisms or viruses falling into the categories of bacteria, viruses, parasites, and fungi
- However, our understanding of the biodiversity that exists is ever-evolving and changing.
- The below picture is a nice visualization we will consider—the study of microbiology is the study of bacteria, archaea, fungi, protists, and algae, and their “theatre of activity,” including viruses!

Image from: Berg, G., Rybakova, D., Fischer, D. et al. Microbiome definition re-visited: old concepts and new challenges. Microbiome 8, 103 (2020). https://doi.org/10.1186/s40168-020-00875-0. License CC-BY.
Course Meeting Times
Lectures: 1 session / week, 2 hours / session
Prerequisites
There are no absolute prerequisites. However, a background knowledge of genetics, biochemistry, and cell biology is expected. Ideally, students have successfully taken at least one of the following classes: 7.03 Genetics, 7.05 General Biochemistry, 7.06 Cell Biology, 7.08 Fundamentals of Chemical Biology, 7.21 Microbial Physiology, or 7.28 Molecular Biology.
Course Description
Your war against pathogenic microbes has begun. It started with a urinary tract infection that you countered by drinking lots of cranberry juice. The second attack was directed at your sense of smell and taste. Your body was in a fight with COVID-19 which was won by your body’s immunity T cells. You celebrate your victory over COVID-19 with a hike and a steak dinner with friends. However, due to a tick bite you received on the hike, you had a severe allergic reaction to the beef! You have had a streak of extremely bad luck: Why did you lose your sense of smell? How can a tick bite cause a meat allergy? And did the cranberry juice do anything to help cure your urinary tract infection? To answer these and other questions, we are going to take a dive into the molecular world of microbes.
In this class, we will use the primary research literature to explore the molecular interactions between pathogens and their hosts that allow microbes to cause infectious diseases. We will examine the factors that pathogens use to colonize a host and how the host response can impact the outcome of the infection. During this course, students will learn (1) how various microbes interact with their hosts to cause diseases; (2) how the host responds in an attempt to stay healthy (and how this sometimes backfires!); (3) the methods researchers use to study these processes; and (4) how to critically read, evaluate, and discuss the primary research literature.
We will highlight how microbes are important for and utilized in both academic and industrial biomedical careers. This will include a field trip to a commercial laboratory that develops exciting new microbial products to better human health. By the end of the class, students will have both developed critical scientific skills in evaluating scientific literature and an appreciation of the microbes influencing our lives and health every day.
Intended Learning Outcomes
By the end of this course, students will be able to do the following:
- Identify mechanisms by which microbes shape human health
- Appreciate both the historical background and the modern-day status of host-pathogen interactions
- Understand and articulate how microbes interact with their hosts to cause various infectious diseases
- Navigate primary research articles, quickly identifying and summarizing the key points and experiments
- Critically analyze the experimental design, results, and conclusions of primary research articles
- Interpret data from a variety of different experimental systems, model organisms, and data types
- Design rigorous follow-up experiments to test the authors’ conclusions
- Recognize that an understanding of microbiology is important for both academic and industrial biomedical careers
Course Expectations
- During the first class, we will introduce ourselves, discuss the course logistics, and introduce some of the broad, overreaching concepts to be covered. We will discuss how to critically read scientific journal articles to provide a basis for the rest of the class. We will also discuss ways to search and access the primary literature using PubMed, Google Scholar, and MIT library resources. All subsequent class meetings will involve active discussions of two related assigned papers, as outlined in the Course Calendar section below.
- The primary objective is for students to learn to read and critically discuss primary scientific literature. Students should understand how to effectively and quickly dissect a scientific paper. Other important skills include understanding experimental design, identifying appropriate experimental controls, interpreting data, and designing the next steps.
- To be successful in this course, students should come to class prepared to discuss the content of the assigned papers, including the main question addressed in the paper, the figures (main and supplementary), tables, methods used, and the main conclusions.
- To ensure everyone is prepared for class discussions, each student will send the instructor brief written answers to a few basic questions about each article. Details are explained on the Assignments page.
- Over the semester, there will be two longer assignments, one written and one oral, described on the Assignments page.
- To assist you with understanding new experimental methods and concepts, at the end of each class the instructor will briefly introduce key topics and methods required to understand the papers assigned for the following class.
- This class is for you!!! To get the most out of class, engaging in the discussions during class is essential. Engaging in critical analysis of articles can be intimidating, but we will improve these skills together. Therefore, ask questions, share your thoughts, and engage in (kind and thoughtful) debate and discussion with your classmates. We are here to learn together. Please reach out if there is a way the instructor can help you reach your full potential in this class.
Grading
This course will be graded as pass/fail (6 units). To earn a passing grade, students are expected to a) attend all class sessions and participate actively (and fulfill any make-up assignments) and b) appropriately complete both the written and oral assignments.
Inclusivity Statement by the Instructor
As the instructor, I value an inclusive environment and community within my classroom. I will treat all students in my classroom with the utmost dignity and respect. I welcome individuals of all backgrounds, beliefs, ethnicities, national origins, gender identities, sexual orientations, religious and political affiliations, and other visible and non-visible differences. All members of this class are expected to contribute to a respectful, welcoming, and inclusive environment for every other member of the class. This is a learning environment; therefore, all should feel comfortable contributing to the discussion and asking questions. If this standard is not being upheld, please feel free to speak with me.
Other Tools/Resources/Tips
- You may want to download a citation manager, such as Mendeley or Zotero, to keep track of the papers you read and to help insert citations into your written assignment. I recommend Zotero. However, if you work in a research laboratory, ask what others in your lab are using. Lab members typically use the same program, allowing them to easily share papers across the lab.
- If you are struggling to understand a method or topic, check out iBiology, YouTube, or JoVE. iBiology and YouTube have some good videos about scientific content. JoVE has videos about experimental methods to help you understand practically what is going on.
- If you want to learn more about why critically reading journal articles is important check out Retraction Watch and MicrobiomDigest on X (Twitter).
If you just love microbes and want to learn more…
For an engaging read:
Strathdee, Steffanie A., Teresa Barker, and Thomas L. Patterson. 2020. The Perfect Predator : A Scientist’s Race to Save Her Husband from a Deadly Superbug : A Memoir. First trade paperback ed. Hachette Books. ISBN: 9780316418119.
For the podcast lovers:
This Week in Microbiology (TWiM) podcast. Hosted by Vincent Racaniello, with co-hosts Elio Schaechter, Michael Schmidt, Michele Swanson and Petra Levin. American Society for Microbiology (ASM).
This Week in Parasitology (TWiP) podcast. Hosted by Vincent Racaniello, Dick Despommier, and Daniel Griffin, MD. American Society for Microbiology (ASM).
This Week in Virology (TWiP) podcast. Hosted by Vincent Racaniello, Dick Despommier, Alan Dove, Rich Condit, Kathy Spindler, and Brianne Barker. American Society for Microbiology (ASM).
Calendar
Week | Topics |
---|---|
1 | Welcome to the “Battlefield”—Introduction to Host-Pathogen Interactions and How to Effectively Read Journal Articles |
2 | Identify the Enemy—Koch’s Postulates |
3 | The World’s Deadliest Infectious Disease—Tuberculosis |
4 |
On the Front Lines—How Bacteria Can Stake Their Claim on the Battlefield Paper for Midterm assignment will be provided. |
5 | Not All Microbes Are Bad—Field Trip Preparation |
6 |
Field Trip!!! Concerto Biosciences Written Assignment Due |
7 | Preprint Week—and the Mysterious Hepatitis Outbreak |
8 | Illness Is Sweeping through the Ranks—Norovirus (Winter Vomiting Bug) |
9 | Biological Sex, Pregnancy, and Infectious Diseases—Malaria |
10 |
Friendly Fire—How the Immune System Can Go Awry, and a Tick Bite Can Lead to Allergic Reactions to Meat Final Presentation Topic Due |
11 | A Battle You Have Been a Part of—The Global Fight Against COVID-19 |
12 | What Is Your Favorite (or Least Favorite) Microbe? |
13 | The Final Battle—Oral Presentations |