Scialdone, Antonio
(2010)
Statistical mechanics of genome regulation: the case of X chromosome inactivation.
[Tesi di dottorato]
(Inedito)
Abstract
The aim of my PhD research project was to discover the mechanisms behind X Chromosome Inactivation (XCI) one of the most
intriguing issues of the current mammalian Biology. XCI is the process whereby a female mammal cell silences one of its two X chromosomes randomly chosen, to equalize the dosage of X products with respect to males (having just one X). We used theoretical models from Statistical Physics and their massive computer simulations to dissect this chromosome-wide stochastic regulatory process.
The importance of these investigations goes beyond the XCI, as the comprehension of this process, can indeed shed light on a whole class of regulatory mechanisms involving the genome.
By means of our quantitive models, which already found some important experimental confirmations, we were able to provide a new deeper level of understanding of the underlying physical and molecular mechanisms. Precise predictions are given for many genetic/chemical manipulations and a new generation of experiments can be designed. A close interplay between theory and experiments, was guaranteed in our project by the collaboration with an experimental group from Harvard Medical School, USA.
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