Suggested Paper Topics for Biochemistry 674, Fall 2001

J. Kahn, 11/5/01

Track the historical development of the thinking on your topic, and/or go into more depth on an experimental technique than we were able to cover in class. It will probably be easiest to look for review articles or methods papers of various ages as a start. Focus on what experiments were done to cause our understanding to change, or on how the sophistication used to approach the method or the data increases. If there is still ignorance or controversy today, explain why, give your reasoning for what the truth is, and/or suggest experiments that could resolve or at least clarify the issue. The paper should be ≤10 pages (not counting figures), double spaced, no more than 30 references. Please include reference titles. I recommend EndNote as a bibliography management program. I remind you that my personal limit for plagiarism is six consecutive words copied without citation. You are welcome to discuss your findings with others in the class, but all written work is to be yours and yours alone, and written solely for this course.

You are welcome to come up with your own topic. I have restricted myself to topics that we have at least tangentially covered, but you can draw on outside knowledge to pick a topic as long as you focus on the nucleic acids end of the topic for your paper.

Please turn in a one-paragraph preview of your paper on Nov. 13. Papers are due Dec. 11, and will be returned at the final exam.

  1. What is the evidence for sequence-dependent flexibility, especially the flexibility of AT-rich base pairs? (E.g. as discussed in TBP crystal structure papers by Sigler, Burley)
  2. Do leucine zipper proteins bend DNA? (Crothers, Kerppola)
  3. How does lac repressor occupy its sites so efficiently? (Müller-Hill, Schleif, von Hippel)
  4. Do proteins slide on DNA to find their binding sites? (von Hippel, Müller-Hill, Reich)
  5. Is Z-DNA relevant to biology? (Rich)
  6. Does TrpR really use water-mediated hydrogen bonds for specific DNA recognition? (Sigler, Müller-Hill)
  7. What is the “nucleosome paradox,” and has it really been resolved? (Morse, Klug, Prunell)
  8. What does the tat-TAR complex look like? (Williamson, Karn)
  9. What is the direction and atomic origin of A-tract induced bending? (Crothers, Dickerson)
  10. What is the evidence for “gating” by Topoisomerase II? (Wang)
  11. How do synthetases recognize tRNAs? Is there a unique mechanism? (Abelson, Uhlenbeck, Schimmel)
  12. What is required for the induction of transcriptional supercoiling? (Wang, Liu)
  13. How does RNA tertiary structure form? (Williamson, Woodson, Pan)
  14. Trace the development of techniques for identifying which protein is actually bound to a given site in vivo (ChIP, mass spec methods).
  15. What are some of the considerations involved in deciding how to handle microarray data? How large does a change in expression have to be before it is believable (P. Brown, R. Young)?
  16. Trace methods scientists use to enhance the specificity and stability of DNA hybridization, for example chemical modification, solution additives, etc.
  17. How can we distinguish catalytic and structural roles for counterions necessary for the folding of RNA enzymes? (Doudna, Burke)
  18. What are the key unresolved issues in how the proposed RNA world might have been launched? (Orgel, Pace)
  19. Could Celera really have sequenced the human genome without using publicly available mapping data? (Venter, Lander)
  20. How has PCR been used in various approaches to site-directed mutagenesis? What is currently the most efficient method?