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


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.


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  

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.


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.


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