Final Project: Eric Yixin Yang – Mathematical Model of Autophagy Activation Pathway

Autophagy is a highly orchestrated degradative process that sequesters and degrades damaged or excess organelles in response to internal and external stress including starvation, oxygen limitation, microbial invasion and hormonal stimulation. The understanding of biochemical pathway of autophagy is important in determining the fate of cells that respond to stress including the challenge of chemotherapeutic agents. This project attempts to build a mathematical model for the activation of autophagy by nutrient deprivation (low concentration of amino acids) with feedback loop when the amino acids generated by protein lysosomal degradation increases the amino acid pool. To achieve this goal, I use MATLAB and XPP learned from the CSHL CCB summer course to build this model and do analysis. The model successfully simulates the change of amino acid level as a response to different nutrient status by autophagy. The system displays oscillation of amino acids level in both nutrient starvation and nutrient enriched status, but does not shows oscillation if starting from the steady state. Total amino acids eventually reach the same level regardless of the initial nutrient status. The bifurcation analysis confirms the simulation result.

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