Principles of design and operation in genetic and biochemical systems. Adaptive responses of yea

Resumen

The aim of this thesis is the development of methodological tools focused on the identification of principies of design and operation in genètic and biochemical systems. First, a mathematical model of the central metabolism of yeast allows the in silico exploration of the performance of hypothetical gene expression changes after a heat shock. Under the hypothesis that exist several evolutive pressures that shaped the actual adaptive profile, the alternative scenarios thatfulfill all the constraints are compared with those that do not. This allows answering the question that will be the leitmotiv of this thesis: Why a given design or operational response has been selected instead of others? The criteria that conform the definition of performance were used to evaluate each of the hypothetical's gene expression profiles and also those providing from microarray experiments with several enyironmental stresses. Second, among all the experimental conditions, only heat shock conditions were selected. Although this specificity, stress responses trigger some changes that are common. For instance in most of them, the celi protein content changes in order to tune the effectiveness of the performance. The most econòmic is a response, the higher chance of being selected. And this ¡s reflected ¡n the over-all protein properties such as the molecular weight. Third, theoretical approximations with mathematical models permit test<ng evaluative hypothesis, make reliable predictions, and explore the laws that govern system behaviours. The complexity of biological systems requireis a language other than simple causal logic to understand the laws that determine system behaviour. There are múltiple formalisms that may characterize the same network. Canonical forms, such as Power-Iaw, offer the possibility of ¡implementing the model in a systematic way and even it is 'possible to incorporate qualitative information. In this work the ¡idiosyncrasy, validity, and scope each of main formalisms is analyzed. Moreover, here is presented the Saturable and Cooperative formalism. It has a great feasibility for quantitative descriptions and it is specially indicated when the saturation and cooperative play a crucial role in the system behaviour. Fourth, models require parameters; and parameters, literature mining. Mew molecular techniques provide a huge amount of data. Bioinformatics can help in integrating information from different sources. In this thesis an extensive review of computational tools are presented. Most of the elements and relationships of the céll are fairly well characterized. However, a ho! istic point of view is needed to shed light on undetermined rules, regulations, and causes.