| LEC # | TOPICS | READINGS |
|---|---|---|
| 1 | Course Introduction Model networks involved in signaling - Signals that start outside of the cell (role of the ECM) and trigger cascades inside the cell, ultimately affecting gene expression | Hunter, Peter J., and Thomas K. Borg. "Integration from Proteins to Organs: The Physiome Project." Nature Reviews 4 (March 2003): 237-243. Kitano, Hiroaki. "Systems Biology: A Brief Overview." Science 295 (March 1, 2002): 1662-1664. |
| 2 | Information flow in the reverse direction - from DNA to RNA to protein (the central dogma) Review of regulatory circuits and introduction to the concept of evolutionary genomics Key Issues: DNA replication and repair errors lead to mutations. Loss of mismatch repair leads to a hyper-Rec phenotype, which facilitates horizontal gene transfer (antibiotic resistance, etc.) | McAdams, Harley H., et al. "The Evolution of Genetic Regulatory Systems in Bacteria." Nature Reviews (Genetics) 5 (March 2004): 1-9. This paper on evolution of genetic regulatory systems will also introduce the third major topic of the course, chemotaxis; Also read the section on DNA structure and base hydrogen bonding properties from a good biochemistry book. |
| 3 | Decoding Information I (Transcription Regulation) | Denamur, Erick, et al. "Evolutionary Implication of the Frequent Horizontal Transfer of Mismatch Repair Genes." Cell 103 (November 22, 2000): 711-721. Read as a follow up to the previous paper; this paper shows how the principles in the McAdams paper could be implemented operationally; Also read section on transcription from a good biochemistry book |
| 4 | Modeling Macromolecular Structure I Individual Homework Assignments | Macromolecular Structure Page (Includes links to genomics and proteomics databases.) |
| 5 | Decoding Information II (Translation) | Read the section on translation from a good biochemistry text Sancar, Aziz, et al. "Molecular Mechanisms of Mammalian DNA Replain and the DNA Damage Checkpoints." Annu. Rev. Biochem. 73 (2004): 39-85. |
| 6 | Modeling Macromolecular Structure II Students Present Homework | |
| 7 | Roundtable Discussion | |
| Examination 1 | ||
| 8 | How to Write an NIH Grant Proposal | |
| 9 | Analysis of the Interferon Network (The JAK/STAT system) | Katze, Michael G., et al. "Viruses and Interferon: A Fight for Supremacy." Nature Reviews 2 (September 2002): 675-687. Pawson, Tony, and Piers Nash. "Assembly of Cell Regulatory Systems Through Protein Interaction Domains." Science 300 (April 18, 2003): 445-452. |
| 10 | Analysis of the Interferon Network | Chen, Xiaomin, et al. "Crystal Structure of a Tyrosine Phosphorylated STAT-1 Dimer Bound to DNA." Cell 93 (May 29, 1998): 827-839. Look at this Web page for a good introduction. |
| 11 | Analysis of the Interferon Network (cont.) | Taniguchi, Tadatsugu, et al. "IRF Family of Transcription Factors as Regulators of Host Defense." Ann. Rev. Immunol. 19 (2001): 623-655. |
| 12 | Analysis of the Interferon Network (cont.) | Example Paper on NO from Last Year |
| 13 | Roundtable 1: Students Present Model Projects on Apoptosis | |
| 14 | Chemotaxis I - How Salvage Pathways Supplement Core Biochemical Pathways The Che System Receptor Methylation as a Mechanism of Control of Chemotaxis | Webre, Daniel J., et al. "Bacterial Chemotaxis." Current Biology 13, no. 2, pp. 47-49. Levit, Mikhail N., and Jeffry B. Stock. "Receptor Methylation Controls the Magnitude of Stimulus-response Coupling in Bacterial Chemotaxis." The Journal of Biological Chemistry 277, no. 29 (September 27, 2002): 36769-36765. Alon, U., et al. "Robustness in Bacterial Chemotaxis." Nature 397 (January 14, 1999): 168-171. Taniguchi, Tadatsugu, et al. "IRF Family of Transcription Factors as Regulators of Host Defense." Ann. Rev. Immunol. 19 (2001): 623-655. |
| 15 | Chemotaxis II - How CheY(P) Signals to the Flagellar Motor Chemiosmotic Coupling Chemotaxis III - Proton Pumps | Berg, Howard C. "The Rotary Motor of Bacterial Flagella." Annual Review of Biochemistry 72 (2003): 19-54. Also please look at this Web site. There is a terrific animation on assembly of the rotary flagellar motor. |
| 16 | Introduction to the Extracellular Matrix Roundtable 2 Will be Delayed for a Few Weeks | Schmeichel, Karen L., and Mina J. Bissell. "Modeling Tissue-specific Signaling and Organ Function in Three Dimensions." Journal of Cell Science 116, no. 12: 2377-2388. Davies, Jamie A. "Extracellular Matrix." In Encyclopedia of Life Sciences. Nature Publishing Group, 2001. Dow, Julian A. T., and Shireen A. Davies. "Integrative Physiology and Functional Genomics of Epithelial Function in a Genetic Model Organism." Physiol. Rev. 83 (2003): 657-729. Parmar, Hema, and Gerald R. Cunha. "Epithelial-stromal Interactions in the Mouse and Human Mammary Gland in Vivo." Endocrine-Related Cancer 11 (2004): 437-458. |
| 17 | Epithelial Cell Morphogenesis Signaling Hierarchy I | Taddei, Ilaria, et al. "Integrins in Mammary Gland Development and Differentiation of Mammary Epithelium." Journal of Mammary Gland Biology and Neoplasia 8, no. 4 (October 2003): 383-394. Liu, Hong, et al. "Polarity and Proliferation are Controlled by Distinct Signaling Pathwaysdownstream of PI3-kinase in Epithelial Tumor Cells." Journal of Cell Biology 164, no. 4 (February 16, 2004): 603-612. Brisken, Cathrin, et al. "IGF-2 is a Mediator of Prolactin-induced Morphogenesis in the Breast." Developmental Cell 3 (December 2002): 877-887. |
| 18 | Epithelial Cell Morphogenesis Signaling Hierarchy II | Brinckerhoff, Constance E., and Lynn M. Matrisian. "Matrix Metalloproteinases: A Tail of a Frog that became a Prince." Nature Reviews (Molecular Cell Biology) 3 (March 2002): 207-214. Leist, Marcel, and Marja Jaattela. "Four Deaths and a Funeral: From Caspases to Alternative Mechanisms." Nature Reviews (Molecular Cell Biology) 2 (August 2001): 1-10. Krissansen, Geoffrey Wayne. "Integrin Superfamily." In Encyclopedia of Life Sciences. Nature Publishing Group, 2001. Miranti, Cindy K., and Joan S. Brugge. "Sensing the Environment: A Historical Perspective on Integrin Signal Transduction." Nature Cell Biology 4 (April 2002): 83-90. Insall, Robert, and Laura Machesky. "Cytoskeleton." In Encyclopedia of Life Sciences. New York: Nature Publishing Group, 2001. Sasisekharan, Ram, and James R. Myette. "The Sweet Science of Glycobiology." American Scientist 91 (September-October 2003): 432-441. Ridley, Anne J., et al. "Cell Migration: Integrating Signals From Front to Back." Science 302 (December 5, 2003): 1704-1709. |
| 19 | Round Table Discussion | |
| 20 | Epithelial Cell Morphogenesis Signaling Hierarchy III | Chodosh, Lewis et al. "Protein Kinase Expression during Murine Mammary Development." Developmental Biology 219 (2000): 259-276. Padera, Robert, et al. "FGF-2/Fibroblast Growth Factor Receptor/Hepartin-like Glycosaminoglycan Interactions: A Compensation Model for FGF-2 Signaling." The FASEB Journal 13 (October 1999): 1677-1687. Tan, John L., et al. "Cells Lying on a Bed of Microneedles: An Approach to Isolate Mechanical Force." Proceedings of the National Academy of Sciences 100, no. 4 (18 February, 2003): 1484-1489. Wiseman, Paul W., et al. "Spatial Mapping of Integrin Interactions and Dynamics During Cell Migration by Image Correlation Microscopy." Journal of Cell Science 117, no. 23, pp. 5521-5534. |
| Examination 2 | ||
| 21 | Roundtable 3 | |
| 22 | Changes in Lung Epithelium During Pathogenesis I | Corry, David B. "Emerging Immune Targets for the Therapy of Allergic Asthma." Nature Reviews (Drug Discovery) 1 (January 2002): 55-64. Niiro, Hiroaki, and Edward A. Clark. "Regulation of B-cell Fate by Antigen-receptor Signals." Nature Reviews (Immunology) 2 (December 2002): 945-956. Koretzky, Gary A., and Peggy S. Myung. "Positive and Negative Regulation of T-cell Activation by Adaptor Proteins." Nature Reviews (Immunology) 1 (November 2001): 95-97. |
| 23 | Changes in Lung Epithelium During Pathogenesis II | |
| 24 | Network Example: Functional Glycomics | |
| Final Papers Due |