http://erzsoregan.voices.wooster.edu/Haoyu-Jiang/

Autophagy, as a cell self-degradation process, responds to the low nutrition level environment via various signaling pathways. Autophagy is an important cellular response in keeping the cell homeostasis. The purpose for this Independent project is to figuring out whether the cell would undergo autophagy or other cellular activates with short pulse of nutrition supply. We used the Boolean model to represent the signaling pathways of the autophagy formation. Our goal for this project is to determine the cellular responses under different environmental conditions. We set three different experimental inputs: growth factors, amino acid, and glucose. The Boolean model shows that the cells would undergo autophagy if we block either amino acid or glucose. Additionally, our result suggests that the cells stay in the senescent state instead of go into autophagy because Reactive Oxygen species (ROS) prohibit the main Autophagy related genes (Atg). Overall, our model mimics the cellular responses under unfavored condition via autophagy successfully. Understanding the mechanism of autophagy could contribute to the medicine field in fighting with several diseases.

Figure 1. Loss of glucose in cycling cells triggers autophagy and arrest, while in senescent cells it leads to mitochondrial dysfunction with no autophagy. Left: time course of Boolean node activity in response to glucose withdrawal in cycling cells, showing a reversible arrest of cycling and engagement of autophagy (red module, middle). Right: time course in response to glucose withdrawal in a senescent cell (see yellow module), showing no autphagy but a change in mitochondrial homeostasis indicating mitochondrial dysfunction-associated senescence.