Data di Pubblicazione:
2018
Citazione:
DYNAMICAL FEEDBACK MODELS IN CELLULAR BIOPHYSICS / F. Cola ; coordinatore: F Ragusa ; supervisor: G. Tiana. DIPARTIMENTO DI FISICA, 2018 Nov 20. 31. ciclo, Anno Accademico 2018. [10.13130/cola-filippo_phd2018-11-20].
Abstract:
In the present PhD thesis we collected two distinct contributions to the field
of mathematical modelling of complex biological phenomena (at the cellular
and subcellular level), with the tools of differential equations and spatial
stochastic simulations.
In the first part we develop a method to determine whether oscillatory
temporal signals are a common feature of genetic regulatory networks or they
require a fine-tuning of the coupling parameters between nodes of the
networks. Modelling a two-nodes genetic network with a system of coupled
delay differential equations, we performed a Monte Carlo sampling of the
space of parameters of the system, biasing the search in favor of highly
oscillating solutions. Estimating with thermodynamic techniques the fraction
of the parameters' space associated with oscillations, we conclude that
oscillations are indeed a rare feature of these biological control systems.
Their dependence on the values of the parameters has been analysed,
revealing some simple patterns.
In the second part we propose a simple theoretical model for the dynamics of
cancer cells subpopulations as observed in experiments in vitro, where a
populations of melanoma cells reacts to the depletion of most of its cancer
stem cells (a small subpopulation with supposed stem-cells properties and
tumorigenic potential) with a large overshoot in the fraction of CSC before
returning to homeostatic values. Our model, consisting in a system of delay
differential equations, is able to reproduce quite well experimental data and
to provide a clear picture of the cellular and molecular details of the control
mechanisms, based on experimental evidence and on the emerging paradigm
of phenotypic plasticity of cancer cells. A multiscale hybrid-continuum
stochastic spatial model on a 2D lattice is also developed to investigate the
spatial distribution of cells within the growing tumour, to be verified in
immunohistochemistry experiments, with particular regard to CSCs
clusterization.
Tipologia IRIS:
Tesi di dottorato
Elenco autori:
F. Cola
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