AbstractsBiology & Animal Science

A network-based approach to cell metabolism: from structure to flux balances

by Oriol Güell Riera

Institution: Universitat de Barcelona
Year: 2015
Keywords: Metabolisme cel·lular; Metabolismo celular; Cell metabolism; Biologia de sistemes; Biología de sistemas; Systems biology; Química física; Physical and theoretical chemistry; Ciències Experimentals i Matemàtiques
Record ID: 1123848
Full text PDF: http://hdl.handle.net/10803/292364


The thesis called “A network-based approach to cell metabolism: from structure to flux balances” shows how the vision of cell metabolism as a whole allows to unveil new mechanisms and responses impossible to reach by traditional reductionist approaches. Different lines of research have been used, and each one has allowed extracting new insights about the properties of cell metabolism of three organisms, Mycoplasma pneumoniae, Escherichia coli, and Staphylococcus aureus. To do so, tools that belong to the complex network science and Systems Biology have been used. The first line of study analyzes how the structure of the metabolic networks of the three mentioned organisms respond when their metabolic networks are affected by perturbations, i.e., when a reaction or a set of them are forced to be non-operative. To do this, the applied algorithm spreads a structural cascade when an initial reaction is forced to be non-operative. This study determines that evolutionary pressure favors the ability of efficient metabolic regulation at the expense of losing robustness to reaction failures. The second line of study focuses on the application of the technique called Flux Balance Analysis (FBA), which is able to compute the fluxes of all reactions composing a metabolic network, assuming that the biological target of the organism is to maximize maximizes the growth rate. The study of synthetic lethal pairs in E. coli and M. pneumoniae with FBA allows identifying two protection mechanisms called plasticity and redundancy. Plasticity sets up as a backup mechanism that is able to reorganize metabolic fluxes turning on inactive reactions when coessential counterparts are removed in order to maintain viability in a specific medium. Redundancy corresponds to a simultaneous use of different flux channels that ensures viability and besides increases growth. The third part combines FBA and the technique called Disparity Filter in E. coli and M. pneumoniae to obtain metabolic backbones, which are reduced versions of metabolic networks composed by the most relevant connections, this relevancy being determined by the importance of the chemical fluxes. One finds that the disparity filter recognizes metabolic connections that are important for long-term evolution, these connections being related to ancestral pathways. In addition, the disparity filter identifies metabolic connections that are important for short-term adaptation. These connections are related to pathways whose reactions quickly adapt to external stimuli. The last line of study studies whether the assumption of maximizing the growth rate leads to a representative solution or not. Although FBA gives a single solution, there exist a number of other possible solutions that are chemically feasible but that do not maximize growth, and that form part of the whole flux space. In this way, the third line of study computes all the possible solutions, obtaining in this way the whole space of flux solutions of E. coli. The information content in the whole space of solutions provides…