In the Classroom
Does Active Learning through an Antisense Jigsaw Make Sense? Mahadevan Seetharaman*,† Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455-0421; *
[email protected] Karin Musier-Forsyth Department of Chemistry, University of Minnesota, Minneapolis, MN 55455-0421
As a graduate student participating in the Preparing Future Faculty (PFF) program (1) at the University of Minnesota, one of us (M. S.) was expected to teach (2) several classes for a faculty mentor (K. M. -F.). In partial fulfillment of this requirement, two lectures on antisense–antigene technology were prepared as part of a nucleic acids chemistry course taken by first-year graduate and advanced-undergraduate students (3). Inspired by an active learning strategy discussed in the PFF course, we chose to implement a “jigsaw” into one of the two classes. Prior to this experience, none of the students in the class knew what a jigsaw was and had not participated in one before. A jigsaw, by definition a puzzle of reassembling, is a cooperative learning strategy (4) in which students read different articles that are complementary to each other and then discuss their articles in small groups (Figure 1). Briefly, the students discuss their article first with others in the class who have read the same article, defined as the “home group”. Generally, the class is divided into as many home groups as the number of articles you require the students to read. Typically three to five articles work well, with the number depending somewhat on the class size and the time available for the exercise. Following the home group discussions, each student contributes the knowledge gleaned from their article to a discussion with class members who did not read the same article. The idea is for each student to contribute a piece of the whole concept or “puzzle”. These “away groups” are formed by reassembling into as many groups as there are members present in the smallest home group. Finally, the information is tied together during a classwide discussion, with a key point being that the students have actively participated in the entire process. Antisense Jigsaw The antisense jigsaw assignment was preceded by an hour-long lecture on the basic concepts in nucleic acid antisense–antigene technology, including RNase H cleavage, triplex formation, and ribozymes. Technical hurdles including nuclease cleavage, delivery to target, and specificity were also covered. For the jigsaw exercise itself, which was carried out on day two, three articles were selected for discussion. Each article reviewed different antisense oligonucleotide modification strategies that were designed to overcome common problems with this approach. The articles were freely available online and students were given links to the Web sites and two days to read their assigned paper. † Current address: Department of Chemistry, University of Minnesota, Minneapolis, MN 55455-0421
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Students assigned an article on antisense modification
Meet in HOME GROUP (discuss article for 5 min with students who read the same article)
Meet in AWAY GROUP (teach article to others in group - 5 min each)
Discuss all 3 articles with entire class (15 min)
Figure 1. Schematic of the antisense jigsaw.
Each of the papers begins with a basic introduction of the antisense concept, including the author’s perspectives on the pros and cons of the therapy and the rationale behind the specific nucleic acid modification being reviewed in the article. The articles chosen for this exercise complemented each other in that they covered three different types of antisense modification strategies, including phosphorothioates (5), 2′ sugar modifications (6), and backbone phosphoramidate analogs (7). Mixed backbone strategies were also discussed in the articles. On the day of the jigsaw discussion, the 12 students in the class formed three groups, one for each article, and spent five minutes in these home group discussions. A list of topics was handed out to guide this initial discussion of the main points of each article (List 1). Next, the students reassembled into four groups of three members each, wherein no group member had read the same article. During these away group discussions, each student was given approximately five minutes to teach their article to the others in their group. After
Journal of Chemical Education • Vol. 80 No. 12 December 2003 • JChemEd.chem.wisc.edu
In the Classroom
List 1. Key Points for Discussion of Articles on Antisense Modifications Antisense or antigene therapy Nuclease resistance Ability to cross cell membranes and pharmacokinetics Binding affinity and specificity RNase H activity, triplex formation, nonspecific binding Sugar conformations—C2′ endo, C3′ endo 3′ or 5′ End modifications Advantages and disadvantages of the respective modifications
You are a graduate student synthesizing small molecules as anticancer agents and frustrated with your research, which is not going particularly well. One day you discover that the gene sequence of the protein that you are targeting has two 20-nucleotide stretches that are unique and not present in any other human genes. The two 20-mer sequences are (Note: only one strand of the gene sequence is given): Target 1: 5'-C G C G C G T A T A T A T A C G C G C G-3' Target 2: 5'-G A G A G A G G G G A G A G A A A A G A-3'
Recently, you have been to a lecture on antisense–antigene therapeutics and you are inspired to apply this approach in your research. Question 1 a. Design an antisense oligonucleotide for one target and an antigene oligo for the other. Provide the sequence and explain if the drug will be RNA- or DNA-based.
15 minutes, an additional five minutes was allotted for groups to wrap up their discussion and talk about the topic as a whole and the connection between all three articles. Finally all articles were discussed with the entire class for 15 minutes. For actively participating in this jigsaw, the students received 50% credit towards a problem set, which constituted 5% of their final grade. At the end of the discussion, a problem set was distributed to the class (Figure 2). The problem set was designed to test the students’ understanding of the concepts and the readings, and served as a measure of how successful we were in our jigsaw exercise. Results On the day of the jigsaw, we noted that conversation among the students about the journal articles had started even before the class had officially begun. When the students were asked to form their home groups, they were initially a little hesitant to start the discussion. However, once we initiated the discussion along certain lines the students caught on very well, with the level of comfort increasing further as they switched into their away groups. The home and away group discussions took more time than the planned 5 and 20 minutes, respectively. Most of the students actively participated in the classwide, post-jigsaw discussion, which lasted for about 20 minutes. A problem set designed to test the students’ level of understanding of the reading materials was distributed at the end of the class period (Figure 2). Based on Bloom’s taxonomy (8), our problem set required the students to understand the fundamentals of antisense therapeutic strategies, to synthesize the three jigsaw readings, apply their knowledge in the design of an antisense drug, and to analyze the reasoning behind their design. Interestingly, rather than basing their answers on the paper they were assigned to read, almost all of the students suggested phosphoramidate modification as the most promising approach. All of the students appeared to understand the concepts that were presented and the main points of all three readings, irrespective of the particular article they were initially assigned to read and present. Based on the problem set evaluations, we were satisfied that the jigsaw exercise was a success.
b. Explain the general strategy you will use (e.g., triplex/ RNase H/ribozyme) and why you chose the particular strategy for each target. c. What modifications will you use to optimize the drug’s activity and improve the likelihood that your strategy will work in vivo? Explain any additional considerations that went into your design. Question 2 Which of the two targets or strategies described in Question 1 do you think has the greatest chance for success as a drug? Why? In your answer, include the advantages and disadvantages of each that helped you reach your decision. Figure 2. Problem set on antisense–antigene therapy.
Discussion Although it is not essential, we felt that giving students some credit for their participation in the jigsaw likely helped to increase the quality of the discussion. It was clear from the away group discussions that the students carefully read their assigned articles. Encouraging students to teach each other in small groups can also be an effective way to help shy students get comfortable with the class and feel less intimidated than, for example, requiring them to give an oral presentation in front of the entire class. The jigsaw can even act as a “warm-up” exercise for a more formal class presentation. Doing a jigsaw or other active learning exercise early in a course is also advantageous in helping students feel comfortable participating in the class; the enthusiasm continues the entire semester. Another important advantage of a jigsaw is that, in a period of 45–50 minutes, multiple articles can be taught effectively. Thus, one can cover a lot of material with the students actively participating in the process of learning. One of the caveats of doing a jigsaw exercise is that the instructor must read all of the assigned articles beforehand and take the
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In the Classroom
time to prepare relevant and interesting questions to guide the discussion. Monitoring the student discussions is one of the most challenging aspects of a jigsaw. Although there were four groups in our exercise, two instructors were present, making it easier to circulate and observe the discussion of all the groups. We found it was less intimidating for the students if we actually sat down with each group to listen and contribute to the discussion rather than hovering over the groups. A larger group of students requires more planning on the part of the instructor and might necessitate the inclusion of a teaching assistant for comonitoring. Handing out key points for discussion (List 1) provides a valuable means of guiding the discussion along the desired lines. In our initial antisense jigsaw, we handed out the discussion topics on the day of the exercise. An alternative strategy is to distribute the points for discussion beforehand so that the students can prepare notes ahead of time. In later exercises we used this approach and found that it did appear to further facilitate the discussion. Jigsaws afford a great deal of flexibility in defining student roles, and instructors may ask participants to do more than just read and discuss articles. A specialized form of a jigsaw involves writing specific tasks on a piece of paper and handing it out to every student in a group. In this manner, each student is assigned specific responsibilities. For example, one task may be to ask group members to identify the biggest advantage of the method or the technique presented in their respective articles. Another person could be asked to record minutes for the entire group. These minutes could be handed in at the end of class to help ensure that students take the exercise seriously. Someone else could be asked to report the salient points evolving from their discussion to the entire class. Despite the fact that literature articles and other scientific readings are very commonly assigned to students as an integral part of graduate-level courses in chemistry and biochemistry, to our knowledge, jigsaws have not been extensively used as a pedagogical tool at this level. Essentially any topic can be taught using a jigsaw, and based on our experience in a graduate-level nucleic acids course, it is an excellent way to get students to critically read the literature, while at the same time learning a new topic and enhancing communication skills. According to the learning pyramid (9), students learn the maximum quantity of content when they teach others or when they immediately apply their learning. The intrinsic nature of a jigsaw is such that it combines both the lecture and discussion component into one active learning exercise. It requires the students not only to read articles, but to talk about them in small groups, teach each other what they have learned, and eventually participate in a discussion with the entire class. Such assignments not only encourage students to critically read the scientific literature, but also give them a chance to hone their communication and presentation skills. Two traditional measures of the success of a teaching strategy are student exam performance and course evaluations. On the final exam for the course, several questions were directly related to the topics covered in the jigsaw exercises. The students generally performed better in answering these
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questions than they did on questions covering topics taught using a more standard lecture format. Student comments from the final course evaluations also indicated that they uniformly enjoyed the jigsaw exercises and felt they were beneficial. The following are quotes taken directly from the student evaluations: “Jigsaw exercises were valuable”, “I thought the jigsaw exercises were really helpful for helping people to think about the material”, “I liked the jigsaws and the oral presentations with class discussions”, “I thought the jigsaws and problem sets were helpful in learning and understanding the material”, “Jigsaw articles were also good; helped analyze scientific papers”, “I got a lot out of the jigsaw exercises”. Additional Jigsaws Jigsaws can be very effective pedagogical tools, and based on our experience, 3–5 jigsaw exercises is probably an appropriate number to incorporate into a 15-week semester course. In addition to the antisense jigsaw described above, two additional topics were taught using the jigsaw method during the nucleic acids course. A second jigsaw covered hammerhead ribozymes (10), and a third exercise covered zinc finger DNA-binding motifs (11). In brief, the second jigsaw included three recent studies aimed at understanding functional aspects of the hammerhead ribozyme, while the third jigsaw focused on DNA recognition by zinc finger binding proteins. Since all articles are not read by all students prior to discussion, one important consideration in designing a jigsaw exercise is to choose related articles containing similar background or introductory material. In two cases (antisense and hammerhead), we selected papers that discussed different approaches to the same problem, and in one case (zinc fingers) we chose three articles from the same lab that built on one another. We found that the latter two topics were as equally well suited to the jigsaw format as the antisense topic. Conclusions An antisense jigsaw was successfully implemented in a graduate-level nucleic acids chemistry course. In the jigsaw, every student was responsible for reading and teaching one of three complementary articles on antisense modification in a small-group format. Based on several evaluation methods, including observation of class participation, a problem set distributed immediately after the jigsaw exercise, a final exam, and course evaluations, we found that the jigsaw was an extremely effective pedagogical tool at the graduate and advanced-undergraduate level. The students seemed to gain and, importantly, retain an understanding of the essential concepts, and to enjoy and benefit from the exercise. Designing a jigsaw for inclusion at the beginning of the semester can help shy students feel more comfortable and is likely to more generally help increase student participation and enthusiasm for the class. In conclusion, a jigsaw is an effective teaching strategy that caters to diversity in learning styles, can be used to foster active learning, and should be easily adaptable to a wide variety of topics covered in graduate-level chemistry and biochemistry courses.
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In the Classroom
Acknowledgments We would like to thank Archana Purushotham and Deborah A. Wingert for useful suggestions and stimulating discussions. Literature Cited 1. Preparing Future Faculty Program. http://www1.umn.edu/ohr/ pff/ (accessed Aug 2003). 2. Mentoring opportunity. http://www1.umn.edu/ohr/teachlearn/ pff/mentoring.html (accessed Aug 2003). 3. Bioorganic III: The Chemistry of Nucleic Acids. Spring 2002. http://www.chem.umn.edu/class/5413/musier02s/ (accessed Aug 2003). 4. Aronson, E.; Blaney, N.; Stephen, C.; Sikes, J.; Snapp, M. The Jigsaw Classroom; Sage Publications: Beverly Hills, CA, 1978. 5. Agrawal, S. Biochim. Biophys. Acta, 1999, 1489, 53–68. 6. Manoharan, M. Biochim. Biophys. Acta, 1999, 1489, 117–130.
7. Gryaznov, S. M. Biochim. Biophys. Acta, 1999, 1489, 131– 140. 8. Bloom, B. S.; Englehart, M. B.; Furst, E. J; Hill, W. H.; Krathwohl, D. R. Taxonomy of Educational Objectives: The Classification of Educational Goals, Handbook I: Cognitive Domain; Longmans, Green: New York, 1956. 9. Learning Pyramid Home Page. http://lowery.tamu.edu/Teaming/ Morgan1/tsld023.htm (accessed Aug 2003). 10. (a) Peracchi, A.; Beigelman, L.; Usman, N.; Herschlag, D. Proc. Natl. Acad. Sci. 1996, 93, 11522–11527. (b) Murray, J. B.; Terwey, D. P.; Maloney, L.; Karpeisky, A.; Usman, N.; Beigelman, L.; Scott, W. G. Cell 1998, 92, 666–673. (c) O’Rear, J. L.; Wang, S.; Feig, A. L.; Beigelman, L.; Uhlenbeck, O. C.; Herschlag, D. RNA 2001, 7, 537–545. 11. (a) Greisman, H. A.; Pabo, C. O. Science 1997, 275, 657– 661. (b) Wolfe, S. A.; Grant, R. A.; Elrod-Erickson, M.; Pabo, C. O. Structure 2001, 9, 717–723. (c) Elrod-Erickson, M.; Pabo, C. O. J. Biol. Chem. 1999, 27, 19281–19285.
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