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Structure Function and Evolution of the Graham Cromar and Dr. John Parkinson Program in Molecular Structure and Function Hospital for Sick Children Toronto, ON, CANADA Committee Members: Dr. Johanna Rommens Dr. Andrew Emili Dr. Gary Bader In the lab: Dr. Jose Peregrin-Alvarez, Dr. James Wasmuth, Chris Sanford, David He Extracellular Matrix Forms diverse structures • • • • • • Biological processes Diseases • • • • Bone Ligament Tendon Vessel Connective tissue Skin • • • • • Adhesion Mechanical support Migration Proliferation Signalling Arthritis Atherosclerosis Cancer Asthma Aims How is the Extracellular Matrix organized? List of components? Organization? Functional units? How did the ECM network evolve? When did functional units arise? Associated adaptations? Are they conserved? Map known disease genes onto the functional map to understand how the ECM is involved in health and disease. Methods Protein Databases Uniprot RefSeq Ensembl Filter Cellular Component = ECM Biological Process Molecular Function Gene Ontology Render Interaction Databases DIP BioGRID Database of ECM proteins Search IntAct Mint The network was constructed, then expanded using orthologues Mouse 613 4 190 354 Human Human 28 807 Mouse 1611 1267 166 Rat 69 463 69 Rat Mouse – 2268 Rat – 1910 Human - 1165 Human - 2252 • Network analysis and Functional annotation • Additional interaction datasets • More organisms: Fly, Worm, Fish, Chicken, Sponge, Hydra Interesting biological results? Predict 8,3,1,2,4 18,12 Verify Share • Wet lab experiments • Cell passage of tagged ECM proteins • Coimmunoprecipitation • Online resource • Web tools 14,8,17,25 5,7,6,9 5,6,11,12,23
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