20.109(F13): Mod 2 Day 1 System Design

Introduction

Today we will begin our journey through Systems Biology and the careful consideration of experimental and computational design that is required for large-scale biological engineering studies. At the end of lab today, you will choose two chemical inhibitors that target the Epidermal Growth Factor Receptor (EGFR) signaling network with the goal of overcoming a growing common problem in the treatment of disease -- drug resistance.

Part 1: Simulation of the EGFR network

There are many approaches to computational modeling that each aim to understand how information travels through a signaling network and ultimately produces a cell phenotype.

1. Open CellDesigner
2. Under Database choose "Import model from BioModels.net..."
   • A large list of models opens in a subwindow.
   • Scroll all the way down to the bottom and choose BIOMD0000000452 Bidkhori2012 - normal EGFR signaling
     • Note: only models that have been curated (or validated) by an SBML expert are shown in the list
   • Click Description to go to the BioModels database and read the abstract that describes the model.
   • Click Reference to see the official paper reference -- notice how computational modeling of biological systems is happening all around the world!
   • Finally, click Import to load the model into CellDesigner. (You may ignore the two errors at this point.)
3. Next, clean up the CellDesigner workspace a bit to make things easier to view:
   1. Maximize the CellDesigner window.
   2. Under View:
      • unselect 'Show Reaction Id'
      • under 'Change Toolbar Visible', select 'Hide all'
4. Click the Proteins near the bottom of the window. How many proteins and protein-complexes are described by this model?
5. Click Reactions. How many different ODEs are used the describe this biochemical system?
6. Now, minimize the bottom panel using the small, gray arrows in the upper left hand corner.
7. The components of the EGFR network and their complexed states (for example EGF + EGFR --> EGF-EGFR) are illustrated in the large window in the middle of the screen. The number of model components makes it very difficult to view the structure of the model. To see a quick view of the system, under View choose 'Show Bird's Eye View'. This will allow you to see a zoomed-out depiction of the model.
8. The 'rats nest' view of the model includes arrows (edges) and boxes (nodes) that represent the different biochemical reactions of the system. To better organize the model for ease of visualizing the information flow, go to Layout and choose Hierarchic Layout.