Stochastic models and dynamic measures for the characterization of bistable circuits

Giampieri, Enrico (2012) Stochastic models and dynamic measures for the characterization of bistable circuits, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Fisica, 24 Ciclo. DOI 10.6092/unibo/amsdottorato/4298.
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During the last few years, a great deal of interest has risen concerning the applications of stochastic methods to several biochemical and biological phenomena. Phenomena like gene expression, cellular memory, bet-hedging strategy in bacterial growth and many others, cannot be described by continuous stochastic models due to their intrinsic discreteness and randomness. In this thesis I have used the Chemical Master Equation (CME) technique to modelize some feedback cycles and analyzing their properties, including experimental data. In the first part of this work, the effect of stochastic stability is discussed on a toy model of the genetic switch that triggers the cellular division, which malfunctioning is known to be one of the hallmarks of cancer. The second system I have worked on is the so-called futile cycle, a closed cycle of two enzymatic reactions that adds and removes a chemical compound, called phosphate group, to a specific substrate. I have thus investigated how adding noise to the enzyme (that is usually in the order of few hundred molecules) modifies the probability of observing a specific number of phosphorylated substrate molecules, and confirmed theoretical predictions with numerical simulations. In the third part the results of the study of a chain of multiple phosphorylation-dephosphorylation cycles will be presented. We will discuss an approximation method for the exact solution in the bidimensional case and the relationship that this method has with the thermodynamic properties of the system, which is an open system far from equilibrium.In the last section the agreement between the theoretical prediction of the total protein quantity in a mouse cells population and the observed quantity will be shown, measured via fluorescence microscopy.

Tipologia del documento
Tesi di dottorato
Giampieri, Enrico
Dottorato di ricerca
Scuola di dottorato
Scienze matematiche, fisiche ed astronomiche
Settore disciplinare
Settore concorsuale
Parole chiave
Master Equation, Stochastic processes, Biophysics, bistability, probability distributions, cellular memory
Data di discussione
16 Marzo 2012

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