Biophysical models for cellular dynamics: applications to metabolic pathways and microtubules kinetics

Computational tools allow the simulation of biological processes giving results which can be used to build computational/experimental approaches for the study of cellular processes dynamics. In my Doctoral Thesis I described and applied calculation methods for the quantitative analysis of the dynamics of different cellular processes. The first chapter describes the mathematical and computational methods then used in the applications described in the following chapters: the first part describes the detailed kinetic models based on ordinary differential equations (ODEs) and the topographic and stoichiometric models to simulate the cellular metabolism of microorganisms. Particular attention is given to the application of an hybrid method: the structural kinetic modelling (SKM). The second part describes some computational methods proposed in literature for the time-series images analysis obtained with confocal microscopy on living cells. Calculation methods described allow the automated detection and tracking of microtubules comets. The second chapter describes my research activities in the application of the quantitative methods to the analysis of metabolic pathways in microorganisms. The application of ODEs and SKM methods are described and through computational simulations the output variation in kinetic parameters are analyzed respect to the perturbations in the input kinetic parameters. The parameter estimation is described through the comparison between experimental and simulation data and a method to build a difference index of kinetic parameters is suggested for build a computational/experimental approach to the analysis of cellular metabolism of microorganisms. The third chapter describes my research activities on the analysis of images obtained from confocal microscopy. Applications of computational methods for detection and tracking of microtubules comets are described. Microtubules dynamics are determined through the analysis of the growing of the microtubules plus ends by the study of EB3 protein made fluorescently by translational fusion with GFP. These methods have been applied to the study of the effects of the inactivation of the Citron kinase protein on the microtubules dynamics and on the angle of the mitotic spindle.