BIO624: Case studies in hypotheses-driven molecular and cellular biology

        [Cr:4, Lc:3, Tt:0, Lb:0]

Course Outline

• Students will be exposed to twelve case-studies involving the formulation of hypotheses in different domains of molecular biology, and the design and execution of experiments shedding light on the correctness of these hypotheses. Topics covered will be chosen from the following:
  • Immune responses to protein aggregates.
  • Replication-driven transcription of bacterial genes.
  • Transcription-driven transcription of bacterial genes.
  • Chromatin remodeling and mid-blastula genome-wide activation of genes in animal development.
  • Helix/sheet architecture & topology in beta/alpha barrel protein folding.
  • Building mirror-imaged proteins using `retro' and `inverso' polypeptides.
  • Building ultra-stable protein structures through engineering of the cooperativity of global unfolding.
  • Protein skin grafting through remodelling of beta sheet surfaces.
  • Use of DNA sequencing to discover translation-inhibiting messenger RNA structures.
  • Molecular recognition in the formation of amyloid/amorphous protein aggregates.
  • Rational reengineering of protein surfaces to block aggregation.
  • Protein domain-swapping interactions and optically-useful biomaterials.

Recommended Reading

• P. Delves, S. Martin, D. Burton and I. Roitt, Roitt's Essential Immunology, 11th Edn., Wiley-Blackwell (2006).
• T. E. Creighton, Proteins : Structure and Molecular Properties, 2nd Edn., W. H. Freeman (1992).
• B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts and P. Walter, Molecular Biology of the Cell, 5th Edn., Garland Science (2008).
• S. F. Gilbert, Developmental Biology, 8th Edn., Sinauer Associates Inc. (2006).
• Klein et al. (1997) A crucial role for B cells in neuroinvasive scrapie. Nature 390, 687-690.
• Brewer (1988). When polymerases collide : Replication and the transcriptional organization of the E.coli chromosome. Cell 53, 679-686.
• Liu and Wang (1987). Supercoiling of the DNA template during transcription. Proc. Natl. Acad. Sci. USA 84, 7024-7027. Farber and Petsko (1990) The evolution of alpha/beta barrel enzymes. Trends Biochem. Sci. 15, 228–234. Guichard et al. (1994) Antigenic mimicry of natural L-peptides with retro-inverso-peptidomimetics. Proc. Natl. Acad. Sci. USA 91, 9765-9769.
• Tsou (1993) Conformational flexibility of enzyme active sites. Science 262, 380–381. D'Amico et al. (2003) Activity–stability relationships in extremophilic enzymes. J. Biol Chem. 278, 7891–7896. Sanger & Coulson (1975) A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J. Mol. Biol. 94, 441–448.
• Fink (1998). Protein aggregation: folding aggregates, inclusion bodies and amyloid. Fold. Des. 3, R9-R23 Vassetzky et al. (2000) Rearrangement of chromatin domains during development in Xenopus. Genes Dev. 14, 1541–1552.