Course Description
The focus of the course will be key papers in the scientific literature that provide the discoveries and methods critical to modernmolecular and cell biology. Students will learn how to dissect published literature to evaluate precisely what constitutesan important paper. The themes for the methods and logic course will be broadly applicable to all students interested in modern experimental biology. Students will meet and discuss the themes of a series of papers first by themselves (with assistance of a faculty member) and then participate in an in depth dissection led by the staff

(Direct links to pdfs are listed when available. Access to journals is only available to computers accessing the internet within the UC Berkeley domain.)

Jan. 22 Introduction

Jan.29 JR Variation and Selection

Cairns, J., Overbaugh, J. and Miller, S. (1988). The origin of mutants. Nature 335, 142-5.

McKenzie, G. J., Lee, P. L., Lombardo, M., Hastings, P. J. and Rosenberg, S. M. (2001). SOS Mutator DNA Polymerase IV Functions in Adaptive Mutation and Not Adaptive Amplification. Molecular Cell 7, 571-579.

Hendrickson, H., Slechta, E.S., Bergthorsson, U., Andersson, D.I. and Roth, J.R. (2002). Amplification-mutagenesis: Evidence that "directed" adaptive mutation and general hypermutability result from growth with a selected gene amplification. Proc. Natl. Acad. Sci.U.S.A. 99, 2164-2169.

Plus handout on Luria Delbruck Experiment

Feb. 5 MB Timimg of Events

Danna K. J. and Nathans D. Jr. (1972). Bidirectional Replication of Simian Virus 40 DNA. Proc. Nat. Acad. Sci. U.S.A. 69, 3097-3100.

Miller, A. M. and Nasmyth, K. A. (1984). Role of DNA replication in the repression of silent mating type loci in yeast. Nature 312, 247-251.

Nishitani H, Nurse P. (1995). p65cdc18 plays a major role controlling the initiation of DNA replication in fission yeast. Cell 83, 397-405.

Feb. 12 BM Information Flow

Crick, F. H. C., Barnett, L., Brenner, S. and Watts-Tobin, R. J. (1961). General nature of the genetic code for proteins. Nature 192, 1227-1233.

Boeke, J. D., Garfinkel, D. J., Styles, C. A. and Fink, G. R. (1985). Ty elements transpose through an RNA intermediate. Cell 3, 491-500.

Tonkin, L. A. et al. (2002). RNA editing by ADARs is important for normal behavior in Caenorhabditis elegans. EMBO J. 21, 6025-6035.

Feb. 19 JR Fidelity

Osherovich, L. Z. and Weisman, J. S. (2001). Multiple Gln/Asn-Rich Prion Domains Confer Susceptibility to Induction of the Yeast [PSI+] Prion. Cell 106, 183-194.

Derkatch, R.L., Bradley, M.E., Hong, J.Y. and Liebman, S.W. (2001). Prions affect the appearance of other prions: The story of [PIN+]. Cell 106, 171-182.

Rutherford, S. L., and Lindquist, S. (1998). Hsp90 as a capacitor for morphological evolution. Nature 396, 336-42.

Feb. 26 MB Specificity

Miller J., McLachlan A. D. and Klug A. (1985) Repetitive Zinc-binding domains in the transcription factor III A from Xenopus Oocyctes. EMBO J. 4, 1609-1614.

Pavletich, N. P. and Pabo, C. O. (1991). Zinc Finger-DNA recognition: Crystal Structure of a Zif268-DNA complex at 2.1 A. Science 252, 809-817.

Liu, P.Q., Rebar, E.J., Zhang, L., Liu, Q., Jamieson, A.C., Liang, Y., Qi, H., Li, P.X., Chen, B., Mendel, M.C., Zhong, X., Lee, Y.L., Eisenberg, S.P., Spratt, S.K., Case, C.C. and Wolffe, A.P. (2001) Regulation of an endogenous locus using a panel of designed zinc finger proteins targeted to accessible chromatin regions. Activation of vascular endothelial growth factor A. J Biol Chem. 276, 11323-11334.

March 5 BM Dissection of Pathways

Zamore, P.D., Tuschl, T., Shap, P.A. and Bartel, D.P. (2000). RNAi: double stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell 101, 25-33.

Bernstein, E., Caudy, A.A., Hammond, S.M. and Hannon, G.J. (2001). Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 409, 363-366.

Sijen, R. et al. (2001). On the role of RNA amplification in dsRNA-triggered gene silencing. Cell 107, 465-476.

Grishok, A. et al. (2001). Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell 106, 23-34.

March 12 JR Genomics

Toth, A., Rabitsch, K. P., Gálová, M., Schleiffer, A., Buonomo, S. B. C. and Nasmyth, K. (2000). Functional genomics identifies monopolin: A kinetochore protein required for segregation of homologs during meiosis. Cell 103, 1155-1168.

Tong, A. et al. (2001). Systematic genetic analysis with ordered arrays of yeast deletion mutants. Science 294, 2364-2368.

Birrell, G.W., Brown, J.A., Wu, H.I., Giaever, G., Chu, A.M., Davis, R.W. and Brown, J.M. (2002) Transcriptional response of Saccharomyces cerevisiae to DNA-damaging agents does not identify the genes that protect against these agents. Proc Natl Acad Sci U.S.A. 99, 8778-8783.

March 19 BM Complementation

Pardee, A. B., Jacob, J. and Monod, J. (1959). The genetic control and cytoplasmic expression of "inducibility" in the synthesis of b-galactosidase by E. coli. J. Mol. Biol. 1, 165-178.

Hanafusa, H., Hanafusa, T. and Rubin, H. (1963). The defectiveness of Rous Sarcoma Virus. Proc. Nat. Acad. Sci. U.S.A. 49, 572-580.

Liu, X, Kim, C. N., Yang, J. Jemmerson, R. and Wang, X. (1996). Induction of apoptotic program in cell-free extracts: Requirement for dATP and Cytochrome c. Cell 86, 147-157.

March 26 Spring Break

April 2 MB Tagging

Meselson, M. and Stahl, F.W. (1958). The Replication of DNA in Escherichia Coli. Proc. Nat. Acad. Sci. U.S.A. 44, 671-682.

Hensel, M., Shea, J.E., Gleeson, C., Jones, M.D., Dalton, E. and Holden, D.W. (1995). Simultaneous identification of bacterial virulence genes by negative selection. Science 269, 400-403.

Griffin, B. A., Adams, S. R. and Tsien, R. Y. (1998). Specific covalent labeling of recombinant protein molecules inside live cells. Science 281, 269-72.

April 9 BM Assigning Function

Kelley, R. L., Meller, V. H., Gordadze, P. R., Roman, G., Davis, R. L. and Kuroda, M. I. (1999). Epigenetic spreading of the dosage compensation complex from roX RNA genes into flanking chromatin. Cell 98, 513-522.

Caterina, M.J. et al. (1997). The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389, 816-824.

Brownell J.E. et al. (1996). Tetrahymena histone acetyltransferase A: A homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 84, 843-851.

April 16 MB Affinity

Rigaut, G., Shevchenko, A., Rutz, B., Wilm, M., Mann, M. and Seraphin, B. (1999). A generic protein purification and method for protein complex characterization and proteome exploration. Nature Biotech. 17, 1030-1032.

Alexander, J.M., Nelson, C.A., van Berkel, V., Lau, E.K., Studts, J.M., Brett, T.J., Speck, S.H., Handel, T.M., Virgin, H.W. and Fremont, D.H. (2002). Structural basis of chemokine sequestration by a herpesvirus decoy receptor. Cell 111, 343-56.

Jordt, S.-E. and Julius, D. (2002). Molecular basis for species-specific sensitivity to "hot" chili peppers. Cell 108, 421-430.

April 23 Break

April 30 JR Science and Societal Implications

Wakayama, T., Perry, A. C., Zuccotti, M., Johnson, K. R. and Yanagimachi, R. (1998). Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 394, 369-74.

Wakayama, T., Tabar, V., Rodriquez, I., Perry, A. C., Studer, L. and Mombaerts, P. (2001). Differentiation of Embryonic Stem Cell Lines Generated from Adult Somatic Cells by Nuclear Transfer. Science 292, 740-743.

Shiang, R. et al. (1994). Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell 78, 335-342.

Cibelli, J. B., Lanza, R. P., and West, M. D. (2002). The First Human Clone Embryo. Sci. Am. 286, 44-51. (pdf is not available - print web page)

Lanza R. P., Cibelli, J. B., West, M. D., Dorff, E., Tauer, C. and Green, R. M. (2001). The Ethical Reasons for Stem Cell Research. Science 292, 1299. (pdf is not available - print web page)

DeBellard, M. E. (2001). Phony Ethics. dEbate, May 29, 2001. (pdf is not available, must print from web page)

May 7 Student Presentations

May 13 Student Presentations