Hysteresis in the AKT signaling pathway

Abstract

Life and function of eukaryotic cells are governed by metabolic and signaling pathways. These pathways are constituted by a multitude of organic molecules. Many of these systems exhibit highly nonlinear behavior, caused by different combinations of feedback loops, feedforward loops et cetera. Possible behaviors include bistability, hypersensitivity, robustness and complex dose-response curves. These circumstances increase the difficulty of designing drugs for e.g. cancer treatments and predicting their effectiveness. In a recent study, D.G. Miguez observed an inverted hysteresis loop when treating the AKT-pathway with the small-molecule inhibitor ZSTK. The main objective of this thesis was to build a biologically sound, mathematical model to understand the observed behavior. Furthermore, we tried to reproduce the experiments using a different method.