A One Semester First Year Seminar: An Interdisciplinary Study of the SARS Virus

1. A One Semester First Year Seminar: An Interdisciplinary Study of the SARS Virus Julie B. Ealy Assistant Professor of Chemistry Pennsylvania State University Lehigh Valley 2005

2. First Year Seminar at PSU • Required of all freshman • Skill development • Academic integrity • Sense of community • Active and collaborative learning • Technology • 8 months in preparation

3. Introductions • A sense of community • Listen and interact with different people who individually, but more so collectively, can contribute to a better understanding of disease I really never had a class at our university where I really got to know the class, in class. The class setting was so comfortable.

4. Primary Literature • Objective: • Develop techniques for tackling problems students know little about such as reading a journal article or focusing on a table or graph or figure Science 2003, 302:1519-1522 “Are We Ready for a Pandemic Influenza?” Some words from the article: pandemic, influenza, H7N7, pathogenic, conjunctivitis, serologic, H5N1, virus, vaccine, seroarchaeology, amino acid, cloned

5. Passages • “Influenza viruses are typed according to their hemagglutinin (H) and neuraminidase (N) surface glycoproteins.”, p.1519 • “Transmission from aquatic birds to humans was hypothesized to require infection of an intermediate host, such as the pig, that has both human-specific (α2-6 sialic acid) and avian-specific (α2-3 sialic acid) receptors on its respiratory epithelium.”, p. 1520.

6. Student Comment • One of the first projects that Professor Ealy gave us was just to read over a four page article. My first reaction was confusion. I thought I would be taking notes and writing everything Professor Ealy said down. Instead, we learned how to read every detail of an article. This task might sound easy but it was much harder than it sounded since we had to define words that we had never heard of before.

7. Comments • I haven’t been asked to read and understand articles that are above my knowledge level in any other class. I learned to recognize and examine important points. • Learning how to comprehend a seemingly unapproachable article was a very valuable technique that I learned from this course.

8. Graph/Figure/Table Interpretation www.niaid.nih.gov/sars_meeting.htm Malik Peiris, University of Hong Kong

9. Comment • In this course we developed techniques for… tackling problems that we knew little about. We read articles that weren’t written for normal readers, we researched those articles, understood them, summarized them, and made clear statements about them. We studied subjects in details where we learned how to understand and make statements about graphs, tables, and figures

10. Molecular Modeling – Spartan Pro • utilize computer generated software that permits 3D visualization of molecular images that enhances understanding of molecular structure • Organic bases of RNA – 3D structure, formula, hydrogen bonds • 20 amino bases – name, abbreviation • 21 nucleotides of cDNA for the spike glycoprotein of SARS – identify complementary RNA – aa • Build a beta sheet – 3 amino acids • Build an alpha helix – 8 amino acids

12. Comments • The thing that astonished me was that there are approximately 1256 amino acids that make up the spike glycoprotein. Now that I have seen what a single amino acid looked like, then to think of 1256 of them all linked to each other (for the SARS spike glycoprotein) is amazing. • The Spartan Pro program is a great tool to generate a visual aid as a backup to what we are discussing in class. Because my science background is limited, comprehension of structures is difficult without a picture as reinforcement.

14. Comment • Finally we constructed what is known as an alpha helix. We did this by choosing 8 amino acids…At first glance it looked like something that was unorganized with no structure or shape to it. Although as we proceeded to orient this structure into a different view or angle so we could see down the center I began to see that I was totally wrong about my assumption. …it looked as though there was a clean cut circle that looked right through the middle of all 8 connected amino acids. Also, almost all the nitrogens, oxygens, and some of the carbons and hydrogens were organized around the center.

15. Drugs and Side Effects • Drug assigned – name, side effects, administration, what it treats, structure Lipitor Treats Alzheimer’s patients for memory, thinking, and everyday activities Side effects are nausea, diarrhea, not sleeping well, vomiting and others Drug is administered by mouth in 5mg or 10mg doses

16. Comments • This past week has been very interesting. Every person in the class has talked about a different pharmaceutical drug. It was neat learning about the structures of them and all of the crazy side effects that go along with them. • I must say, doing the assignment of researching the drugs is one that I honestly enjoyed. It was interesting learning more about all the drugs and what made it more interesting was that I was really familiar with the drugs already.

18. SARS Main Proteinase – Atom/AA

19. Comment • Once again, my understanding of this class has been strengthened by the use of 3-dimensional visual aides on the computer. Very similar to the first series of computer exercises I found this one very fascinating and I found that this information will aid in better understanding of this course. I also began to understand from this exercise exactly how complex the protein can be.

20. Comment • We got the chance to look at the different number of alpha helices and beta sheets, along with loops which we had never discussed before. It was interesting to be able to view this image as the cartoon representation, and then switch it an atom view and a plastic model view. These three images allowed me to view them in different aspects, which we didn’t do in our previous computer exercises. It was neat to be able to experience this.

21. Opening Paragraph for Docking • What is seen on the screen is streptavidin, a bacterial protein, complexed with biotin (purple), a ligand (which in this case is a fancy name for a molecule). The structure of the complex was determined in 1989 by Weber, et al. An atom model of streptavidin is displayed where all amino acids and the side chains are visible. A space filling model of biotin is displayed. Biotin is actually vitamin H and is necessary for metabolism and growth in humans. Biotin binds tightly to streptavidin and makes the complex one of interest in research. If the binding of biotin to streptavidin can be understood better, it will aid in the design of new drugs and ligands for proteins and nucleic acids.

22. Biotin Docked into Streptavidin

23. Energy Values for Docking

24. Comments • Another thing I got to use was ICM Pro. I got to look at the structure of the bacterial protein, streptavidin. I had the chance to see biotin docked into the receptor, streptavidin. • The other computer program that we worked with really taught me a lot and I feel like I understand that program. I got a pretty good grasp of the concepts that were presented in the computer exercise about drug docking. It was interesting to see the drug trying to find the perfect spot to dock in.

25. Poster Presentation Topics: influenza, vaccines, economics, origin, spread of SARS, structure of SARS - share knowledge with others through a poster presentation which requires development of strategies for writing across several disciplines - understand that many people work together and contribute to an understanding of a general disease such as influenza, or more specific diseases

26. Poster Presentations • I learned a lot from working within a group especially for this project. • The poster presentations were easier than I thought they were going to be. The topic of our presentation was interesting because it didn’t have to deal with the virus of SARS itself but how it affected the world economically. • Group projects teach many things, with an emphasis on working together with others.

27. Final Comment • When I first walked into this class I had the attitude why do I have to take this class; it has nothing to do with my major and it’s just a waste of time. Although I soon would find out that I was totally wrong with my observations about the course and everything else. I’ve learned more interesting things in this class than I did in any other throughout this semester.

28. References • Abagyan, R., and M.Totrov. 2004. MolSoft, Molecules in Silico. LaJolla, CA. • Amino Acid references: http://www.imb-jena.de/IMAGE_AA.html http://www.biomed.curtin.edu.au/teach/biochem/tutorial/ AAs/AA.html http://web.mit.edu/esgbio/www/lm/proteins/aa/aminoacids. html • Bowen, G. M., Roth, W.-M., & McGinn, M. K. 1999. Interpretations of graphs by university biology students and practicing scientists: Toward a social practice view of scientific representation practices. Journal of Researchin Science Teaching 36: 1020- 1043.

29. Ealy, J. B. 1998. A student evaluation of molecular modeling in first year chemistry. Journal of Science Education and Technology 8: 309-321. • Ealy, J. B. 2004. Students' understanding is enhanced through molecular modeling. Paper accepted for publication, Journal of Science Education and Technology. • Kozma, R. B. 1997. Multimedia and understanding: Expert and novice responses to different representations of chemical phenomena. Journal of Research in Science Teaching 34: 949-968. • Lowery, M. S. & Plesniak, L. A. 2003. Some like it cold: A computer-based laboratory introduction to sequence and tertiary structure comparison of cold-adapted lactate dehydrogenases using bioinformatics tools. Journal of Chemical Education 80: 1300.

30. Martin, N. H. 1998. Integration of computational chemistry into the chemistry curriculum. Journal of Chemical Education 75: 2, 241-243. • NCBI Sequence Viewer. 2003. GenBank accession numbers. AY274119. Available online at http://www.ncbi.nlm.nih.gov/entrez/viewer. • NIAID. 2003. SARS: Developing a research response. May 30. Available online at http://www.niaid.nih.gov/sars_meeting.htm. • Peterson, R. R. & Cox, J. R. (2001). Integrating computational chemistry into a project-oriented biochemistry laboratory experience: A new twist on the lysozyme experiment. Journal of Chemical Education 78:1551.

31. Roth, W.-M., Bowen, G. M., & McGinn, M. K. 1999. Differences in graph related practices between high school biology textbooks and scientific ecology journals. Journal of Researchin Science Teaching 36: 977- 1019. • Shusterman, G. P. & Shusterman, A. J. 1997. Teaching chemistry with electron density models. Journal of Chemical Education 74: 771 • Wavefunction, Inc. Irvine, CA. • Webby, R. J., and R. G. Webster. 2003. Are we ready for pandemic influenza? Science 302: 1519-1522.