creating a network using an app called Netsim (the app only works on Ipad) (genetic biology)

profilemoonlight2018
ExampleofaNetSimsubmission.docx

Example of a NetSim submission

Here I mapped a genetic network controlling the differentiation of intestinal progenitors in the fruit fly (Drosophila melanogaster), based on a research article describing the role of a gene called escargot (Esg) in controlling the maintenance and differentiation of these progenitors (summarized in the attached figure from the article) {1}. In these cells, Esg inhibits the expression of differentiation genes, keeping these cells as progenitors. Therefore, I set up an inhibitory link between Esg and differentiation genes. Because Esg is only expressed in progenitor cells, I also drew an inhibitory connection from differentiation genes back to Esg, to reflect the fact that when differentiation genes do their job the expression of Esg will be reduced.

In my network I also drew an inhibitory connection from Esg to Amun, another one from Amun to Notch and a positive interaction from Notch to differentiation genes (as indicated in the diagram). Finally, in the article the authors used RNAi-mediated knockdown of Esg expression to inhibit the activity of Esg within progenitor cells, which I modeled by adding a node called "esgRNAi" that inhibits the node "Esg". To simulate the state of normal cells, the start value of "esgRNAi" is set to "0.0"; but having a start value for this node that is greater than 0 will simulate what happens to cells when the esgRNAi is expressed experimentally to inhibit Esg.

For start values, I chose "0" for differentiation genes, to reflect the fact that these genes must be OFF in cells that have not started to differentiate yet. For "Esg" and "Notch" I chose arbitrary values of "50". I had also chosen "50" for "Amun", but I noticed that it caused the differentiation genes to never turn ON, which is probably not good. So I lowered the start value progressively, and noticed that the lower the initial value of "Amun", the longer that a cell can remain as a progenitor, until it eventually differentiates (i.e. differentiation genes turn ON and Esg turns OFF). I chose to leave the production and deterioration rates at arbitrary values of "0.1" because I have no information indicating that these genes would be spontaneously turning ON or OFF. My choice of interaction strengths was arbitrary, but comparable across the board, because I have no information to justify stronger or weaker interactions throughouth the network. In fact, tweaking some of these interactions strengths shows how the differentiation of cells can be delayed, accelerated and prevented altogether.

As expected, if I give "esgRNAi" a positive value, the differentiation of the progenitor cells is accelerated, as shown in the article.

The share code for my network is: YPNC.