Mathematical and Computational Analysis of Intracelluar Dynamics

Abstract

Two intracellular processes are analyzed using mathematical and computational models. First, the regulation between cell survival and death by the p53-AKT genetic network is studied. The tumor suppressor protein, p53, and the oncoprotein, AKT, are involved in a mutual antagonism feedback. This mutual antagonism is the more significant given that p53 and AKT have opposite effects on apoptosis. The models predict a p53-AKT bistable switch that regulates pro-survival and pro-death states. Furthermore, roles of oscillations of intracellular p53 protein levels on the control of cell survival and death are investigated. Upon substantial DNA damage, p53 oscillations are predicted to sensitize cells towards apoptosis. Second, consequences of co-transcriptional coupling between pre-mRNA elongation and splicing machineries are studied. Particularly, dynamical changes in the co-transcriptional binding accessibilities of antisense-oligonucleotides target sites in the dystrophin pre-mRNA is correlated with their efficiencies to induce exclusion of mutated exon(s), a therapy for Duchenne muscular dystrophy.