May 2010

JBC in the Classroom

Using JBC Articles in an Upper  Level Biophysics Course

 

Box 1. Steps for Evaluating a Journal Article

1. What is the context of the paper?
2. What work by others is critical to the paper?
3. Identify three critical background references.
4. Summarize the big picture aspect of the work.
5. What is the central hypothesis being tested?
6. Identify preparative experiments.
7. What are the critical experiments that test the hypothesis?
8. Which is the most important figure in the paper?
9. What are the major conclusions reached?
10. What evidence are the major conclusions based on?
11. What is the reproducibility of the experimental data and how might this affect the conclusions that will be reached for each experiment?
12. What controls are used?
13. What are the potential pitfalls of the techniques used?
14. What is the next logical step suggested by the authors?
15. What additional experiments do these results suggest to you?

The challenges facing education in the molecular life sciences have been well documented (1–3). For a number of years, the biology community has advocated using primary literature (4–6), and much has been written about the effectiveness of journal clubs (7) or literature-based courses (8, 9). These courses are ideal for teaching both fundamentals and skills necessary for a major in biochemistry, molecular biology or biophysics.

For the past twenty years, I have taught a course with a significant component of primary literature to biochemistry and molecular biology majors. The course is called “Protein Structure, Function and Biophysics.” Usually, about half the students in the class have had physical chemistry, and the other half is planning to take it the following semester.

The course is divided into the following seven blocks, each two-weeks-long, with a focus on some aspect of structure, function and biophysics:
1. Protein structure: primary, secondary, tertiary and quaternary structure
2. Enzyme kinetics
3. Ligand binding
4. Fluorescence spectroscopy and its uses in biochemistry and biophysics
5. Protein folding, stability and flexibility
6. Structure determination (NMR or x-ray crystallography)
7. Computational approaches (either molecular dynamics or QM-MM approaches)

Each block consists of a two-week lab and the following four lecture sessions:
1. Introductory material: lecture and discussion
2. Discussion of primary literature: small group work and report
3. Quantitative aspects: problem sets, small group work and report
4. Laboratory wrap-up and discussion

Using Primary Literature

I usually assign a Journal of Biological Chemistry paper by Sayer et al., titled “Effect of the Active Site D25N Mutation on the Structure, Stability, and Ligand Binding of the Mature HIV-1 Protease” (10) as a follow-up to an HIV protease problem set that we developed (2). The students have to turn in a written report on the paper before Session 2 of each block using the steps in Box 1 (adapted from reference 11) as guidance.

At the start of the literature discussion class, we break into four groups of four students. Each group is assigned some part of the paper to discuss amongst themselves for about 20-25 minutes (in a 75-minute class). For this paper, I group Figures 1 and 7; Figures 2 and 8; Figures 3, 4 and 9; and Figures 5, 6 and Table 2. After a discussion during which I float between the groups answering queries and asking provocative questions, each group has to explain, in detail, their assigned component to the rest of the class and answer questions. These presentations and discussions generally last about 10 minutes each.

Education
Supplemental Figure S2 from Sayer et al. (10) can produce a nice discussion of what you see in an electron density map and what resolution does for you. Depending on the level of the class and their familiarity with the structure of a PDB file, this figure also can be a useful starting point for discussing a variety of aspects of conformation and conformational flexibility or simply as a tool for looking at the content of a PDB file.

The Sayer paper clearly brings in material from several blocks of the course, which is quite deliberate on my part. It helps to solidify student understanding and pique their interest for an upcoming block, and it plays a crucial role in the material of the block.

An added benefit is a laboratory component associated with each block that often incorporates some of the techniques discussed in the paper. I also have used the paper with blocks focusing on structure stability and ligand binding (see figure). Critical evaluation of the data and figures from the paper really helps with lab write-ups and discussion.

Is It Effective?

I find that the Sayer paper works well in the context of HIV protease. This topic comes up in a number of other courses in the program, and students generally are interested in the topic. The students also really enjoy the literature discussion sessions. It usually is the first time they have been exposed to a critical dissection of a paper. Students also report that the sessions really help them appreciate outside seminar speakers. (I usually try to correlate the papers with topics that I know will be presented in an outside seminar, and have even, on occasion, managed to have the author of the paper give a seminar the week of the discussion.) In at least one block during the course, I deliberately skip the literature discussion session for a paper, and, several blocks later, I have a pop quiz on the topics covered in the paper. I have been pleasantly surprised at how my students’ analysis of a paper, even without the in-class discussion, has led to a more detailed understanding of a topic.

References

1. Bell, E. (2000) Ability to Recite Fails to Excite. Times Higher Ed. July 14.
2. Bell, E. (2001) The Future of Education in the Molecular Life Sciences. Nature Reviews Molecular Cell Biology 2, 221 – 225.
3. National Research Council (2003) Biology 2010: Transforming Undergraduate Education for Future Research Biologists. Washington, D.C., National Academies Press.
4. Mulnix, A. B. (2003) Investigations of Protein Structure and Function Using the Scientific Literature: An Assignment for an Undergraduate Cell Physiology Course. Cell Biology Education 2, 248 – 255.
5. Woodhull-McNeal, A. (1989) Teaching Introductory Science as Inquiry. Coll. Teach. 37, 3 – 7.
6. Janick-Buckner, D. (1997) Getting Undergraduates to Critically Read and Discuss Primary Literature. J. Coll. Sci. Teach. 27, 29 – 32.
7. Glazer, F. S. (2000) Journal Clubs - a Successful Vehicle to Science Literacy. J. College Sci. Teach. 24, 320 – 324.
8. Gillen, C. M. (2006) Criticism and Interpretation: Teaching the Persuasive Aspects of Research Articles. CBE – Life Sciences Education 5, 34 – 38
9. Kozeracki, C. A., Carey, M. F. Colicelli, J., and Levis-Fitzgerald, M. (2006) An Intensive Primary-Literature-based Teaching Program Directly Benefits Undergraduate Science Majors and Facilitates Their Transition to Doctoral Programs. CBE – Life Sciences Education 5, 340 – 347.
10. Sayer, J. M., Liu, F., Ishima, R., Weber, I. T., and Louis, J. M. (2008) Effect of the Active Site D25N Mutation on the Structure, Stability, and Ligand Binding of the Mature HIV-1 Protease. J. Biol. Chem. 283, 13459 – 13470.
11. Bell, E. (2010) Using Research to Teach Introductory Science. BAMBED. In press.

J. Ellis Bell (jbell2@richmond.edu) is professor of chemistry and chair of the biochemistry and molecular biology program at the University of Richmond. He is also chair of the ASBMB Education and Professional Development Committee.


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