Background:
I study Ewing’s family tumors (EFTs), which are pediatric cancers of bone or soft tissue. In cancer, many cell signaling pathways are activated when they should be dormant, causing cells to grow out of control and form tumors. These pathways become activated when external stimuli such as growth factors bind to receptors on the surface of the cell, leading to a cascade of activated proteins that culminates in a change in cell function, such as increased cell growth or inhibition of cell death. For my project, I perturb Ewing’s cells with specific stimuli (addition of IGF-I and inhibition of EWS/FLI1), and then use a technique called tandem mass spectrometry to identify phosphorylated proteins downstream of that stimulus (phosphoproteomics). I then use this data to create networks of proteins that are activated in EFTs. This will allow me to target specific points in the network that are critical for tumor growth. Identification of these critical points may lead to the discovery of new therapeutic targets in EFTs.

The Dance:
Act I represents signal transduction. The piece opens with a cell signaling pathway prior to activation by a growth factor. The dancer on the left represents a receptor that is present on the surface of the cell and the other three dancers onstage represent proteins downstream of the receptor in the pathway. Because the proteins have not been activated, the dance only consists of small movements. As the dance begins, a fifth dancer enters the stage, which represents a growth factor that will bind to the receptor. The lift represents the interaction between the growth factor and the receptor. After this interaction takes place, the receptor undergoes a modification (phosphorylation), which results in activation. Now that the receptor has been activated, the dancer is performing a series of small jumps. Adapter proteins then recognize the phosphorylated receptor, which is represented by two dancers dancing toward the receptor dancer. After this interaction, these two proteins are now activated and join the receptor dancer in the series of small jumps. Now the two proteins will continue to interact with and activate more proteins downstream in the pathway, represented by their movements toward the last dancer in the back. This cascade of activation ultimately results in a change in cell function, which is represented by all the dancers now performing a series of large jumps. The music of the piece also mirrors what happens during signal transduction. It builds from the first interaction (along with the size of the movements) until all the proteins/dancers on stage are activated, reaching the climax as the network becomes fully activated (the series of large jumps).

Act II represents the formation of the networks of activated proteins in EFTs and targeting of critical points within that network. The piece begins with dancers individually entering the stage and sequentially joining the movement. This corresponds to each phosphorylated protein being identified using tandem mass spectrometry after the Ewing’s cells have been perturbed. As the dancers begin dancing in a circle, this represents the beginning of the proteins being assembled into a network. The dancers then form lines and the lines pass through each other, followed by the dancers running around each other. This signifies finding connections between different components of the network based on known interactions between proteins in the cell. The final triangle formation symbolizes the fully constructed network. Since this network is activated in EFTs, the movement while in the triangle formation consists of a series of large jumps, similar to the movement at the culmination of signal transduction in Act I. The soloist represents targeting a specific point in the network. If this point is critical to the cancer, removing this activated protein will result in downstream pathways being shut down, leading to decreased cell growth. So after the soloist leaves the stage, the remaining dancers only perform small movements. This is similar to the movement at the beginning of Act I, which represented proteins that are not activated. Again the music mirrors the science. It builds during the formation of the network, reaching the climax when the network is fully formed and activated, then fades after the removal of a critical component in the network to signify dephosphorylated (not active) proteins and decreased cell growth.