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Mechanisms of spatial organisation within bacterial cells
Due to their small size bacteria were once thought to be bags of proteins relying solely on simple diffusion to carry out all the chemical reactions needed for their survival. However, it is now clear that they have a complex internal organisation, despite lacking the membrane-bound organelles found...
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| Beteiligte: | |
| Format: | Dissertation |
| Sprache: | Englisch |
| Veröffentlicht: |
Philipps-Universität Marburg
2023
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| Online Zugang: | PDF-Volltext |
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| Zusammenfassung: | Due to their small size bacteria were once thought to be bags of proteins relying solely on simple diffusion to carry out all the chemical reactions needed for their survival. However, it is now clear that they have a complex internal organisation, despite lacking the membrane-bound organelles found in eukaryotic cells. Bacteria are able to position proteins precisely, orchestrate protein oscillations, and segregate the chromosome and plasmids successfully. Although contemporary microscopy techniques have illuminated the presence of spatial organisation, the precise molecular interactions underlying these phenomena have remained elusive. To address this, the application of mathematical and physical models emerges as a useful approach to understand the fundamental mechanisms behind bacterial organisation. In this thesis, we leverage mathematical and physical modelling to explore the intricacies of bacterial cell spatial organisation. Our investigation will center on two distinct phenomena: the redistribution of a protein within the Tol-Pal system (as detailed in Part i), and the underlying mechanism governing the segregation of genetic material and low-copy number plasmids by the ParABS system (as detailed in Part ii). Utilising experimental data, we construct models allowing us to decipher the operational mechanisms and interactions between components within these systems. The first part of this thesis employs a deterministic modelling approach to describe protein relocalisation through a system of differential equations. We begin by analytically solving a simplified model that encapsulates the essence of the biological problem. Subsequently, we expand this model to provide a more comprehensive representation of the system, which we solve numerically. We show that proteins can localise using a ’mobilisation and capture’ mechanism. In the second part we pivot to utilise stochastic modelling. Initially, we show that it is theoretically possible for a diffusion based mechanism of protein sliding to explain the observed pattern of spreading on DNA. Then we look at the effects of protein-protein bridges on the DNA and demonstrate how these can organise the DNA into globular states or hairpin and helical structures, depending on bridge lifetime. Combining sliding and bridging into a unified model, we find that short-lived bridges do not impede sliding and can reproduce both the protein binding profile and the expected DNA condensation. Finally, we develop a model for an alternative mechanism of DNA segregation by the ParABS system that can reproduce behaviour observed experimentally. |
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| DOI: | 10.17192/z2024.0064 |