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Kuhr, Jan-Timm (2012): Statistical properties of microbial phenotypes and colony growth: fluctuations in transfection, phenotypic switching and range expansion. Dissertation, LMU München: Faculty of Physics
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Abstract

Cells are the fundamental units of which all life forms are composed. To understand the elementary organization of life, it is therefore meaningful to start the investigation on the single cell level.Modern microscopy permits the examination of both subcellular processes and collective microbial behavior. In this microscopic regime, fluctuations are of eminent importance. As this noise is an inherent property of such systems, life evolved robust systems, which work effectively in spite of severe fluctuations. Moreover, life also makes use of these fluctuations for its benefit. For modeling purposes in this field of research, concepts from statistical mechanics and from the analysis of stochastic processes can be applied to account for the fluctuations. This work is roughly divided into two parts, which also address the background, concepts and literature of the corresponding topics. The first part is concerned with the modeling of intracellular processes, for which noise is important. In this context two publications, which arose from collaborations with experimental biophysicists, are discussed: In gene therapy external genetic material is injected into cells to remedy deficient behavior. To characterize this process, fluorophore encoding plasmids were administered to eukaryotic cells by means of two chemical transfection methods. The distribution of expression levels is explained by several strongly stochastic steps during transfection and subsequent quasi-deterministic gene expression. The second collaboration addresses the switching kinetics between different phenotypes in bacteria. In the case at hand, the emergence of "competence" in B. subtilis is studied. This ability (to take up genetic material from the extracellular medium) is strongly regulated by a network of interacting genes. While the different phenotypes are associated with stable fixed points of non-linear differential equations, switching between phenotypes relies on fluctuations in the small number of mRNA molecules. The second part of this work elaborates on collective, stochastic growth of many cells in an expanding colony. The corresponding manuscript analyzes a theoretical model with methods from statistical mechanics. Microbial colony growth is sometimes seen as a model system for range expansion or colonization processes. Inspired by experiments, a stochastic surface growth process, in the form of a generalized Eden model, is set up and analyzed. The model explicitly takes into account selection between two strains, irreversible mutations, and the roughness of the propagating colony front. The asymmetric character of mutations implies the existence of an absorbing state, where only the mutant strain is at the front of the expanding population. Hence, the model combines two interesting branches of non-equilibrium statistical mechanics: phase transitions to absorbing states and dynamic surface roughening. As usual for these processes, one can define critical exponents, which describe the divergence of observables near the phase transition, and admit organization of models into universality classes. It turns out that the coupling between roughening dynamics and population dynamics induces qualitative different behavior. As a consequence, the model cannot be assigned to any universality class currently known.