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 Bone Ligament Tendon Vessel Connective tissue Skin Biological processes Adhesion Mechanical support Migration Proliferation Signalling Diseases 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 Database of ECM proteins Search IntAct Mint DIP BioGRID Interaction Databases Ensembl Cellular Component = ECM Biological Process Molecular Function Gene Ontology RefSeqUniprot Protein Databases Filter Render
The network was constructed, then expanded using orthologues Rat Mouse Human Rat Mouse Human Mouse – 2268 Rat – 1910 Human Human
Interesting biological results? 8,3,1,2,4 18,12 14,8,17,25 5,7,6,9 5,6,11,12,23 Predict Network analysis and Functional annotation Additional interaction datasets More organisms: Fly, Worm, Fish, Chicken, Sponge, Hydra Verify Wet lab experiments Cell passage of tagged ECM proteins Coimmunoprecipitation Share Online resource Web tools