Case Teaching Notes for
“Take Two and Call Me in the Morning: A Case Study in Cell Structure and Function”

Introduction / Background

This case study is a “clicker case.” It combines the use of student personal response systems (clickers) with case teaching methods and formats. The case is presented in class using a series of PowerPoint slides punctuated by questions (called “clicker questions”) that students respond to before moving on to the next slide. In this way, students work through the material to understand (and solve) the problem presented in the case. Specifically designed for use in large introductory science classes, the method integrates lecture material, case storylines, student discussion, (clicker) questions, the clarification of answers to those questions, more lecture, and data.

This case is intended to teach students about cell structure, function, and evolution. In the case, students encounter a real-life problem—someone exhibiting symptoms of the flu in a college dorm. As they consider what might be the cause of the illness, students are challenged to learn about and then use the basic differences between living organisms (viruses, prokaryotes, eukaryotes) to decide which organism is causing the infection. The basic concept that students need to understand is that although there are certain commonalities to the structures found in all living organisms, there are specific differences that can be used to classify and distinguish life forms.

The second major concept is that the similarities and differences between organisms which have accumulated over the evolution of life on earth are critical to diagnosing and treating diseases caused by pathogenic organisms. For example, differences between bacterial cell walls and those of plants or fungi have been exploited in the development of antibiotics. The importance of this knowledge was emphasized in the Evolution, Science, and Society: Evolutionary Biology and the National Research Agenda Project sponsored by the A. P. Sloan Foundation and the National Science Foundation (1998). The white paper for that project noted that similarities between pathogenic species can provide a launching point for discovering novel disease treatments, and that understanding the rapid rate of evolutionary change and adaptation is critical for determining how likely or quickly an organism might be able to evolve resistance to drugs or evolve higher virulence in the future.

Finally, what is most powerful about this case is that students will want to retain the information because it is useful in their own lives and will aid their understanding of health issues, including why they should not take antibiotics for a viral infection.

The case is designed for use in a one-semester introductory biology course taken primarily by freshmen and sophomores to fulfill a general education requirement. It could be used in any introductory biology course or as a review of cell structure in an anatomy and physiology course.

In preparing for the case, students should receive a brief introduction to the biochemistry of macromolecules (carbohydrates, lipids, proteins, and DNA) and phospholipid membrane structure, as well as a pre-class reading assignment that includes the chapter in their textbook on cell types.

Objectives

• Identify or recall the different structural components and reproductive strategies in prokaryotes, eukaryotes, and viruses.
• Differentiate between prokaryotes, eukaryotes, and viruses using factors such as size or the presence of unique structures.
• Apply knowledge of the differences between viruses, prokaryotes, and eukaryotes to understand why various treatment methods work to specifically kill one class of organisms while remaining harmless to the human cells or other organisms.
• Understand the evidence supporting the endosymbiotic theory (i.e., that membrane-enclosed organelles found in eukaryotes originated as free-living prokaryotes that were engulfed and then maintained because they established a mutually beneficial symbiotic relationship with their host cell).

Misconceptions

• That there are no substantial differences between cells and viruses or between cell types aside from perhaps size.

Classroom Management / Blocks of Analysis

In my class, students are assigned to work on the case in groups of six that have been instituted the first day of the semester. I have used this case successfully in a class of 300 students organized into 50 groups. For more information on how I use permanent groups in my large lecture classes, see the teaching notes for another case study of which I am the author—http://www.sciencecases.org/druid_dracula/druid_dracula_notes.asp—as well as my article Brickman, 2006.

The case takes about 15–20 minutes of student discussion punctuated with mini-lectures lasting 10 minutes so that the entire case is completed by the end of a 75-minute lecture session. Students use their understanding of the differences between cells to fill in several tables on a handout they get in advance to help them prepare for the case, then use that information in class to answer questions that make them clarify relationships, identify differences, interpret data, and explain how they came up with their answers.

Pre-Class Student Preparation

I give the handout with tables from the case on a single sheet of paper before the day we analyze the case. Students are asked to complete Table 1 as a homework assignment (Tables 2 and 3 are completed in class). A copy of the handout with the tables completed can be found in the password-protected answer key for this case (see Answer Key, below). The case moves rapidly through a lot of content, and it is critical that students are prepared with a basic level of knowledge and vocabulary, so having this handout graded in some form is important. If you cannot grade the handout or would like to add some pre-class assessment to make sure students are prepared, a multiple choice web quiz substitute is included in Appendix.

In-Class Case Presentation

The case is presented in class using a series of PowerPoint presentation slides punctuated by multiple choice questions which the students answer using their clickers. On the day of class, I begin by describing the purpose and objectives of the case.

Part I—Opening Story, Metric Review, and Prokaryotes (Slides 1–13)

Slide 2, Slide 3, and Slide 4: Students can either read the opening story about a student in a dorm who comes down with flu-like symptoms, you can read it aloud to them, or you can print it on the handout given to students before class.

In the case story, students are introduced to Becky, a counselor in a freshman dormitory where one of the girls on her floor, Ellie, has gotten sick. Becky and another dorm counselor, Ann, try to figure out what could be the cause of the mysterious illness and what medicine they should take to prevent coming down with it themselves.

Slide 5: Considering the description of the activities the sick student has experienced in the past few days, students are asked to come up with a list of the ways the student could have been exposed to an organism and what one possible organism they think could be the cause of her illness.

Slide 6: Tell students that during the next few minutes of class we will investigate the differences between 5 possible suspects. They should check their homework answers to Table 1 and add any details they missed so that when they hear the results of the Health Center tests they will be able to solve the mystery of what made Ellie sick. They should also fill in possible drug treatments in Table 2 of the handout.

Slide 7: Students learn that the Health Center collected blood samples from Ellie and observed her cells under a light microscope. From these, Health Center staff identified foreign structures with DNA and outer membranes that were negative for the gram stain about 1/10 the size of her cells.

Slide 8: Students are provided with a brief review of the metric system and relative sizes.

Slide 9, Slide 10, and Slide 11: Becky’s Internet search reveals an initial suspect, a bacterium, Coxiella burnetii. Coxiella burnetii is a gram-negative, obligate intracellular parasite. It cannot grow in the absence of a host cell, but has a near-endospore-like resistance to environmental stressors. Remind students to check the answers to the work they put in Table 1.

Slide 12: Clicker question 1 lists three antibiotics and describes how they work. Students must use the description given for Ellie’s illness and demonstrate their understanding of the function of different structures in prokaryotes to select one antibiotic that definitely would NOT work. This is an important and useful point for students: Antibiotics take advantage of specific structures found only in prokaryotes to kill them while not harming our cells. Examples include amoxicillin, penicillin, and other β-lactams, which block the enzyme that normally creates linkages between amino acids in the peptidoglycan molecules found in cell walls. (While penicillin is only effective against gram positive bacteria, semi-synthetic β-lactam antibiotics are effective against both gram positive and gram negative bacteria.) We also discuss streptomycin, which blocks protein synthesis by prokaryotes, and ciprofloxacin hydrochloride (Cipro), which blocks bacterial DNA gyrase enzyme. Cipro works in all prokaryotes because this enzyme is needed to counteract excessive twisting of DNA that occurs when circles of DNA are unwound to be copied into DNA or RNA.

Slide 13: Clicker question 2 asks students to use their recall of the metric system and ability to convert and compare different metric units to tell if an organism that is 1/10 the size of a human cell could be Coxiella, a cell that is 0.3–0.5 µm in size. The correct answer is that they could be, but since most human cells are 10–100 µm in size, as diagrammed on the chart, it is not likely that the organisms in the photos of Ellie’s cells are Coxiella.

Part II—Eukaryotic Cells (Slides 14–25)

Slide 14: The story advances, with Becky and Ann talking at the Health Center. Becky is thinking now that the “little crescent shaped structures” she thought were the bacteria may not be. She notes that “they aren’t too big to be bacteria, but they aren’t too small to be mitochondria or some kind of protozoan parasite.” Ann maintains that they cannot be bacteria.

Slide 15: Show the students the micrograph taken of Ellie’s blood. Ask students if they have any ideas.

Slide 16: Clicker question 3 asks “Which structure is not found in all cells?”

Slide 17: Compares prokaryotes and eukaryotes. I discuss with students the two basic cell types, prokaryotes and eukaryotes, and how they differ in location of DNA, size, single versus multicellular, use of O₂ for metabolism, and the presence of membrane-enclosed organelles. Fungi, plants, animals, and protists are all eukaryotes; bacteria and archeae are prokaryotes.

Slide 18: Becky’s internet search also reveals eukaryotic suspects. The first suspect, Cryptococcus neoformans, is a 2.5–10 µm encapsulated fungus found in decaying pigeon or chicken droppings. It is inhaled as spores that eventually spread to the brain, causing meningoencephalitis. It forms a black pigmented substance that can be seen on bird seed. It has a phospholipid membrane outside as well as inside the cytoplasm separating functions such as gathering and transforming cellular energy and manufacturing macromolecules.

Slide 19 and Slide 20: These slides investigate the second eukaryotic suspect, Toxoplasmosis gondii. Toxoplasma gondii is a 4–6 µm single-celled protozoan parasite of mammals and birds. Human infection is common: 25–40% of American adults have had it, usually with no symptoms—probably acquired through ingesting undercooked meat. Toxoplasma gondii has a sexual life cycle when living in cats, so infection can also follow contact with cat feces. Infection from mother to fetus can result in birth defects (400–4000 U.S. children annually).

Slide 20 contains a link to a webpage displaying a number of short videos in QuickTime format that are optional (see http://www.uvm.edu/microbiology/videos_ward.php?id=23). The clip entitled “Invasion 4” illustrates the ability of the parasite to insert itself into the plasma membrane to cross to the cytoplasm. “Escape 2” shows several parasites bursting open a cell to escape.

Slide 21, Slide 22, and Slide 23: These slides show the basic structure of the eukaryotic cell with characteristics such as size, reproduction, organelles, outer protective layer, etc. The last slide shows a comparison with a plant cell. Remind students to check the answers to the work they put in Table 1 of the handout.

Slide 24: Focuses on several eukaryotic organelles: nucleus and endomembrane system, mitochondria, and chloroplasts.

Slide 25: Clicker question 4 begins with a description of two drugs Becky has in her possession. One of these drugs specifically affects one of the two eukaryotic suspects. They are then asked which test of Ellie’s blood would help them tell which eukaryotic suspect infected her. The correct answer is to determine the presence of β-glucan. Polyenes combine with ergosterol (component of fungal and some bacterial membranes) to disrupt and break membranes, or other drugs inhibit the formation of β-glucan (found in fungal cell walls). These antifungal drugs will only work on fungi, not on the protists. Effective drugs against protozoans include pyrimethamine and sulfonamides, which interfere with folic acid synthesis by inhibiting the enzyme dihydrofolate reductase and dihydropteroate synthetase. Folic acid is needed in the biosynthesis of thymine and uracil nucleotides. Without these nucleotides, the cells will have trouble making RNA or DNA. Human cells would also be affected, so doctors often co-prescribe folinic acid that can be converted to folic acid in human cells without relying on dihydrofolate reductase.

Part III—Viruses (Slides 26–33)

Slide 26: Becky and Ann are back at the dorm waiting for the results of more tests. In the course of their conversation, Becky brings up the possibility that the causative agent may be a virus.

Slide 27, Slide 28, Slide 29, and Slide 30: These slides cover viruses, focusing in particular on two possible “suspects”—influenza and West Nile. Slide 30 is “programmed” as an animation of viral infection and replication.

Slide 31: Describes how influenza infects cells and how Tamiflu works. Tamiflu is an enzyme inhibitor that works on a specific viral enzyme (neuraminidase) that normally digests sialic acid that is on the surface of human cells. Influenza A virus make a protein called hemmaglutanin that sticks to sialic acid on cell surfaces and mucus that helps it enter and exit human cells. If the virus were to remain stuck to the sialic acid, it could not escape the cell to infect other cells. Tamiflu won’t work on other viruses, bacteria, or eukaryotes because they don’t make neuraminidase.

Slide 32: Students take time to discuss with each other their answers to Table 1.

Slide 33: Clicker question 5 checks to see if the students have filled out and can use the information in Table 1. The correct answer is C, because the virus does not have DNA or a cell wall, is about 50 nm, and does not divide sexually or asexually.

Part IV—Genomic Comparison and Conclusion (Slides 34–41)

Slide 34: Students read the next section of the case where Becky and Ann review the results of the analysis of Ellie’s DNA. The sequences are all from a ribosomal DNA gene that all cells must have to make ribosomes, but for which there are many differences between organisms. The similarities of DNA can be described to students as being like a paternity test; children should have more similar DNA to their parents and siblings than to distant relatives or strangers because they had common ancestors. The same is true of all life on earth. They are then asked what they would think the results indicate and how they would apply the differences between the remaining two suspects (a prokaryote and eukaryote) to treat the illness.

Slide 35: Clicker question 6 involves the modern technique of using DNA sequences. The correct answer is the Toxoplasma DNA, which has only one nucleotide difference.

Slide 36: When Becky notes that Ellie’s mitochondrial DNA matches the Coxiella sequence closely, Ann isn’t surprised. Ann tells Becky there is evidence that mitochondria are the descendents of gram-negative bacteria like Coxiella, setting the stage for the next two slides.

Slide 37 and Slide 38: List the evidence that points to mitochondria descending from a prokaryotic ancestor (the endosymbiotic theory). From here I describe endosymbiotic theory. Give students time to fill out Table 3 of the handout showing these differences.

Slide 39: Phylogenetic tree showing the relationship between bacteria, archaea, and eukarya.

Slide 40: Clicker question 7 asks students to match mitochondria to different positions on a tree of life. The correct answer is D, because although mitochondria are only found in eukaryotes, they are thought to be most closely related to gram-negative bacteria.

Slide 41: Conclusion: It was Toxo!

Additional Optional Information about Toxoplasma gondii

The most common means of acquiring the parasite is not from cats, but from undercooked meat. This extremely common parasite infects many livestock animals. The parasite enters the body and divides during a chronic phase after which it encysts in skeletal muscle. When another organism eats this meat, it ingests the microscopic Toxoplasma gondii cysts that can only be killed through proper cooking. Cats become infected by eating animals that have tissue cysts—mostly small rodents and birds. Cats (domestic and wild) are the only animals in which Toxoplasma gondii multiplies sexually, and the resulting cyst is excreted in cat feces. When cysts are first excreted, they are non-viable. They have to incubate in the environment for a few days before they become infective. So, if you change your litterbox every two days, you’re safe even if your cat is infected. If you don’t have a cat, you can still be infected with oocysts from soil and water that cats have defecated in or from produce that has been rinsed with contaminated water or grown in contaminated soil. In rare cases, the parasite has been transmitted via blood transfusion. More commonly, the parasite is passed during an organ transplant.

Toxoplasma gondii can also be transmitted across the placenta from a mother to her fetus, but only if the mother contracts the infection while she is pregnant or just a few weeks before becoming pregnant. If a woman is infected prior to pregnancy, the parasite will be encysted in her tissues, but will not be actively dividing and spreading, so it cannot infect the baby. Only during the acute phase of infection is the baby at risk. Birth defects that result (Congenital Toxoplasmosis) occur 1 in every 10,000 births, or about 400 babies in the U.S. each year. If a woman is infected very early in pregnancy, the parasite usually causes abortion of the fetus. If infected within the first 6 months of pregnancy, the fetus may have damage to the brain. The more severe defects include hydrocephalus (spinal fluid building up between the brain and the skull that puts pressure on the developing brain, causing mental retardation) or blindness.

Assessment

This case was developed as part of an NSF-sponsored grant (# DUE 0618570) to determine whether clicker cases such as this one produced greater learning than the traditional lecture approach. As part of that project, the clicker cases had questions that were asked of students both before and after the class in which the material was presented. The questions were also used again during the final exam.

A transfer question was also developed for the case. This is a question designed to test whether a student could apply the knowledge that was given by the instructor in class to a new situation—a test of higher level thinking, according to Benjamin Bloom’s taxonomy of cognitive domain. This question, together with the additional pre- and post-case questions, are presented in the Answer Key.

Answer Key

Answers to the questions posed in the case study are provided in a separate answer key to the case. Those answers are password-protected. To access the answers for this case, go to the key. You will be prompted for a username and password. If you have not yet registered with us, you can see whether you are eligible for an account by reviewing our password policy and then apply online or write to answerkey@sciencecases.org.

References

Brickman, P. 2006. The case of the Druid Dracula: A directed “clicker” case study on DNA fingerprinting. Journal of College Science Teaching 36(2): 48–53.

Coxiella

http://microbewiki.kenyon.edu/index.php/Coxiella

Last accessed: October 6, 2008

Waller, R.F., et al. 1998. Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum. Proceedings of the National Academy of Sciences of the United States of America 95(21): 12352–12357.

Slide Credits

Acknowledgements: This material is based upon work supported by the NSF Grant No.DUE-0618570. Any opinions, findings, conclusions, or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of NSF. The author appreciates the helpful comments and suggestions from Eric Ribbens, Jonathan Shaver, Nancy Boury, and Maureen Knabb.

Date Posted: November 4, 2008.

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