Manipulating Biology: Costs, Benefits and Controversies

Classroom Activities

The 5-E instructional model will be used to support students’ inquiry into antibiotic resistance, particularly the role of enzymes in structure-based antibiotic design and the development of bacterial resistance. The activities that I will use in each phase of the instructional sequence are described below.

Engage

To pique students’ interest about the topic, I will use images and stories that highlight the importance of antibiotics and the threat of antibiotic resistance. As students enter the room, they will see posters of the World War II penicillin ad²⁶, the World Antibiotics Awareness Week campaign²⁷, and of New York Giants tight end Daniel Fells. Using a KWL chart, students will write down what they know about the topic and the questions that come to mind as they study these posters. They will then watch a news report about Daniel Fell’s fight against MRSA.²⁸ To show how this problem hits close to home, we will also read an excerpt from chapter one of Maryn McKenna’s book, Big Chicken, that describes a San Jose resident who fell victim to the 2013 salmonella outbreak, ²⁹ or watch a news feature about the recent discovery of a new antibiotic at the San Jose IBM Research Center.³⁰ With their elbow partners, students will discuss what they have learned from the book and the news report and write these in their KWL chart. Students will revisit and update this chart as we progress through the unit. Small teams will then convene to review the project entry document that describes the unit’s driving question performance product, and grading rubric. They will establish group norms and assign roles.

Explore

In this phase, students will begin to explore the essential concepts of this unit through a simulation and a couple of inquiry labs.

Antibiotic Resistance Simulation

This whole-class activity will help students visualize how antibiotics exert a selective pressure that favors resistant bacterial strains. Each student will be given a paper bag that represents the bacteria. Inside the bag are 5 colored paper clips (or bingo chips, marbles, or cut-out papers), four of which are of the same color and will represent plasmids carrying no antibiotic resistance genes, and one of a different color to represent a plasmid carrying resistance genes. Students will go around the room and exchange “plasmids” with their classmates without peeking into the bags. After 5 plasmid exchanges, I will spray the room with “antibiotic”. Students will look into their bags and see if they contain resistance genes. If they don’t, they “die” and go back to their seats. More sets of 5 plasmid exchanges will be done until all the remaining bags contain only plasmids carrying resistance genes.

Enzyme Lab

This is a lab that is traditionally done in an AP Biology class. Since only a few of my students have taken the class, it is still worthwhile for them to perform the lab and learn about chemical kinetics and the role of enzymes in chemical reactions. They will vary the concentrations of the substrate and the enzyme and derive the rate law of the reaction. Students will also investigate the effect of an inhibitor on enzyme activity. For this lab, students will use catalase in potato extracts to speed up the decomposition of hydrogen peroxide into water and oxygen. They will use the paper disc method to measure reaction rate. 10% hydroxylamine will be used as the inhibitor.

Chromatographic Separation of Amino Acids

The students’ hands-on experience in this lab will lay the foundation for understanding protein structure and substrate-active site interactions. Students will be given four amino acids and an unknown hydrolyzed protein to separate using paper chromatography. They will determine the retention factor (Rf) of the known amino acids and compare them with the separated amino acids in the unknown sample. They will explain the observed differences in Rf values in terms of the structure and polarity of the amino acid side-chains.

Explain

The antibiotic activity of penicillin will be used to illustrate the concepts of substrate-enzyme interactions. Students will build, interact with, and use models to understand how penicillin works and how bacteria are developing a resistance to it. Prior to creating models students will watch videos and take Cornell notes on protein structure and enzyme action.^{31, 32}

Modeling Amino Acids

Students will view molecular models of various amino acids on MolView (an Open Source web-application). They will take note of the hybridization and geometric shape of the central atoms, identify functional groups, compare the structure of the side-chains, and categorize the amino acids as non-polar, polar, or charged. Working in pairs, students will build a ball-and-stick model of their assigned amino acid. The whole class will then come together and use the models to show how amino acids form peptide bonds. The peptide chain model will be “folded” and students will identify areas where amino acids can form dispersion forces, ionic bonds, ion-dipole interactions, and hydrogen bonds.

Modeling the Mode of Action of β-Lactams and β-Lactamases

Students will first study the structures of three β-lactams: penicillin, amoxicillin, and clavulanic acid on MolView. They will identify the β-lactam ring in these structures.  They will then watch a video on penicillin’s mode of action.³³ To model how penicillin-binding proteins catalyze the cross-linking of the peptidoglycan layers of the bacterial cell wall, students will link paper clips together. Large paper clips of alternating colors will represent the NAG and NAM sugar subunits. Smaller paper clips oriented perpendicular to the large paper clip chains will represent the amino acids that make up the peptide chain. The students’ own hands will represent the penicillin-binding proteins that catalyze the crosslinking of the peptidoglycan chains. To model how penicillin works to inactivate the enzyme, students will use masking tape to wrap their thumb and pointer finger together. They will then try to crosslink the peptidoglycan chains using their “deactivated enzyme”. To model howβ-lactamases break penicillin’sβ-lactam ring, students will use a pair of scissors to cut the tape that binds their fingers together. The “freed enzyme” will once again successfully cross-link the peptidoglycan layers.

Elaborate

Students will apply their newly acquired knowledge to tackle the controversy surrounding the proposed total ban on non-therapeutic and sub-therapeutic use of antibiotics in food-producing animals. They will read several articles on the issue and participate in a class discussion so they can review their understanding of the text and ask clarifying questions. To structure the discussion, I will facilitate an Inner-Outer Circle Discussion (Socratic Seminar) and provide sentence starters for students who struggle to communicate their ideas. Students will be prompted to cite specific evidence from the text to support arguments and counterarguments. The students in the Outer Circle will evaluate the Inner Circle’s performance and the quality of the evidence presented based on the text.

Evaluate

The various activities described above will provide multiple opportunities for me to evaluate student learning. I will use the KWL chart entries, written lab reports, models, notes, worksheets, and class discussions to assess the development of the students’ conceptual understanding. The final performance product is a summative assessment that will provide the students an opportunity to integrate and apply all the concepts learned in this unit.