Coupled dynamical processes in bacteria
The main object of this Thesis is the study of the dynamical coupling between cellular processes, and how this coupling gives rise to a well-defined behavior in the presence of non-linearities and noise. Cell functioning relies on the exquisite coordination between a large number of dynamical nonlin...
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| Tipo de recurso: | tesis doctoral |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Universitat Politècnica de Catalunya (UPC) |
| Repositorio: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglés |
| OAI Identifier: | oai:upcommons.upc.edu:2117/103567 |
| Acceso en línea: | https://hdl.handle.net/2117/103567 https://dx.doi.org/10.5821/dissertation-2117-103567 |
| Access Level: | acceso abierto |
| Palabra clave: | Àrees temàtiques de la UPC::Física |
| Sumario: | The main object of this Thesis is the study of the dynamical coupling between cellular processes, and how this coupling gives rise to a well-defined behavior in the presence of non-linearities and noise. Cell functioning relies on the exquisite coordination between a large number of dynamical nonlinear processes subject to fluctuations, which simultaneously operate within the cell. Many cellular dynamical processes occur in the form of periodic oscillations in the expression and/or activation of proteins. However more complex dynamics have been identified recently in the form of transient pulses occurring at random. These types of dynamical processes do not occur in isolation in a cell but they do so simultaneously, and therefore it is necessary to establish the origin and level of coordination between them. All these issues still remain unanswered. In Part I we introduce and motivate the two types of cellular dynamics studied in this Thesis. Part II is devoted to pulses of protein expression or activity (Chapters 2 and 3), whereas in Part III we concentrate in periodic oscillations in protein expression (Chapter 4). Specifically, in Chapter 2 we focus on how the coupling of certain inputs affect the response of the circuit regulating competence for DNA uptake in Bacillus subtilis. In wild-type cells, under certain environmental stress conditions, competence has been found to follow a stochastic pulsing dynamics. Here we study how the dynamical response of the competence circuit varies from excitable pulses to bistability and oscillations depending on the joint action of two coupled inputs applied to the system. The phenotypical effects reported in this Chapter are caused by changes in the dynamical behavior of the underlying genetic circuit. The stability analysis of a theoretical model of the competence circuit establishes the various dynamical regimes that the circuit can exhibit, which are in very good quantitative agreement with experimental results. Still dealing with pulsing dynamics, in Chapter 3 we study the dynamical coupling between pulses of protein activity in single cells. For that purpose, in collaboration with Prof. M. Elowitz's laboratory from the California Institute of Technology, we concentrated in the alternative sigma factors family in B. subtilis. Sigma factors are proteins that reversibly bind to core RNA polymerase thus giving the formed holoenzyme promoter-recognition properties. In this Chapter we show for the first time that several alternative sigma factors present stochastic pulses in their activation, and that these pulses take place in conditions of competition for core RNA polymerase. In the light of these results, we propose a new mechanism, ¿time-sharing¿, in which sigma factors take turns in order to use most of the available RNA polymerase, with only one or a few sigma factors being simultaneously active in a given cell. We also develop several mathematical models that shed light on how pulsing and competition affect RNAP allocation. In Chapter 4 we study how a synthetic genetic oscillator is coupled to cell division and replication. We took advantage of a synthetic oscillator developed for Escherichia coli in the laboratory of Prof. J. Hasty at the University of California San Diego. We have shown that the bacterial cell cycle is able to partially entrain the synthetic oscillations consistently under normal growth conditions, by driving the periodic replication of the genes involved in the oscillator. We have also shown that synchronization between the two periodic processes increases when the synthetic oscillator is coupled back to cell cycle via the expression of an inhibitor of replication initiation. Additionally, we have developed a computational toy model that confirmed this effect. Finally, in Part IV (Chapter 5) we summarize and discuss the main results presented in this Thesis, and suggest directions for future research. |
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