title: The role of promoter architecture in transduction, integration and multiplexing of environmental signals in bacteria
creator: Kaspar, Sarah
subject: ddc-570
subject: 570 Life sciences
description: For the processing of environmental signals, bacteria often use two-component systems (TCSs), in which a transcription factor (TF) is activated upon phosphorylation. There is a high diversity both in the way in which phosphorylation activates the TF (phospho-mode) and in the archi- tecture of the TCS-driven promoters. In this work, I model gene expression in TCSs in order to study the interplay of promoter architecture and phospho-mode with respect to the distinct processing tasks of signal transduction, integration and multiplexing.  First a comprehensive study implements biologically relevant phospho-modes and investigates their influence on the promoter architectures required for effective signal transduction. This study is also the modeling basis for the whole thesis. I find that effective signal transduction is accomplished by different promoter architectures, depending on the mode of phosphoryla- tion. Further, the phospho-mode also determines to which extent the response shape is tunable through modulations in the promoter architecture.  In the quorum sensing (QS) signaling pathway in Bacillus subtilis, the integration of two signals on the gene expression level is investigated. When only the pathway architecture is considered, both signals seem to converge, since they activate the same TF. However, my model identifies promoter architectural features which allow to control the weighting of the two signals. The meaning of these results is discussed with respect to the evolution of QS-dependent promoters. Finally, based on model-derived promoter design criteria, I suggest a synthetic multiplexing system for experimental use. The purpose of this system is to allow decoding of the two QS signals on the expression level and thus inference on their natural distribution.  The results of this thesis can support the interpretation of promoter sequence data and inform design questions in synthetic biology.
date: 2019
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/26814/1/doktorarbeit_Sarah_Kaspar.pdf
identifier: DOI:10.11588/heidok.00026814
identifier: urn:nbn:de:bsz:16-heidok-268144
identifier:   Kaspar, Sarah  (2019) The role of promoter architecture in transduction, integration and multiplexing of environmental signals in bacteria.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/26814/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng