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Title: Unravelling the role of a eukaryote-like serine/threonine kinase in how Escherichia coli adapts to sustained nitrogen starvation
Author: Switzer, Amy
ISNI:       0000 0004 7659 0502
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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Nitrogen is an essential component of the bacterial cell, thus rapid adaptation to nitrogen starvation is essential for survival. In Escherichia coli and related bacteria the response to nitrogen starvation is initially coordinated by transcriptional reprogramming, and occurs through signalling from the NtrBC two component system, where NtrC is the master transcriptional regulator required for σ54-dependent transcription. This NtrC-coordinated response has been extensively studied and is initially required for "scavenging" of alternative nitrogen sources. The yeaGH operon is one of the most highly upregulated and only uncharacterised operon expressed in an NtrC-dependent manner upon nitrogen starvation. Previous work in the laboratory revealed that the eukaryote-like serine/threonine kinase, YeaG, is required by E. coli to cope with sustained nitrogen starvation. However, the molecular basis by which YeaG achieves this remains elusive. The main objective of the work presented here was to expand on how YeaG contributes to adaptation to sustained nitrogen starvation by using a transcriptomics based approach. Results revealed that YeaG is required throughout nitrogen starvation for repression of two energetically costly pathways, flagellar and methionine biosynthesis, in a temporal manner. Understanding how YeaG affects temporal transcriptome dynamics inspired further research into how the transcriptome is affected during adaptation to sustained nitrogen starvation. Utilising global transcriptome studies, two genes, abgR and yedL, were identified to contribute towards maintenance of viability during sustained nitrogen starvation, and revealed new avenues for investigation of temporal transcriptional adaptation to stress. Overall, this study suggests that adaptation to sustained nitrogen starvation is likely dynamic, and is required for optimal adaptation and maintenance of survival, whilst being prepared to resume growth once nitrogen becomes available. YeaG is required in this adaptive process to act as a temporal metabolic brake in repressing energetically costly pathways, required for survival.
Supervisor: Wigneshweraraj, Sivaramesh ; Brown, Daniel Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral