Filter and export

Publications

What is a Publication?
4 Publications visible to you, out of a total of 4
Towards a Systems Level Understanding of the Oxygen Response of Escherichia coli

Abstract (Expand)

Escherichia coli is a facultatively anaerobic bacterium. With glucose if no external electron acceptors are available, ATP is produced by substrate level phosphorylation. The intracellular redox balance … is maintained by mixed-acid fermentation, that is, the production and excretion of several organic acids. When oxygen is available, E. coli switches to aerobic respiration to achieve redox balance and optimal energy conservation by proton translocation linked to electron transfer. The switch between fermentative and aerobic respiratory growth is driven by extensive changes in gene expression and protein synthesis, resulting in global changes in metabolic fluxes and metabolite concentrations. This oxygen response is determined by the interaction of global and local genetic regulatory mechanisms, as well as by enzymatic regulation. The response is affected by basic physical constraints such as diffusion, thermodynamics and the requirement for a balance of carbon, electrons and energy (predominantly the proton motive force and the ATP pool). A comprehensive systems level understanding of the oxygen response of E. coli requires the integrated interpretation of experimental data that are pertinent to the multiple levels of organization that mediate the response. In the pan-European venture, Systems Biology of Microorganisms (SysMO) and specifically within the project Systems Understanding of Microbial Oxygen Metabolism (SUMO), regulator activities, gene expression, metabolite levels and metabolic flux datasets were obtained using a standardized and reproducible chemostat-based experimental system. These different types and qualities of data were integrated using mathematical models. The approach described here has revealed a much more detailed picture of the aerobic-anaerobic response, especially for the environmentally critical microaerobic range that is located between unlimited oxygen availability and anaerobiosis.

Authors: , , , , , , S. Kunz, , , , , ,

Date Published: 7th May 2014

Publication Type: Not specified

Systems analysis of transcription factor activities in environments with stable and dynamic oxygen concentrations

Abstract (Expand)

Understanding gene regulation requires knowledge of changes in transcription factor (TF) activities. Simultaneous direct measurement of numerous TF activities is currently impossible. Nevertheless, … statistical approaches to infer TF activities have yielded non-trivial and verifiable predictions for individual TFs. Here, global statistical modelling identifies changes in TF activities from transcript profiles of Escherichia coli growing in stable (fixed oxygen availabilities) and dynamic (changing oxygen availability) environments. A core oxygen-responsive TF network, supplemented by additional TFs acting under specific conditions, was identified. The activities of the cytoplasmic oxygen-responsive TF, FNR, and the membrane-bound terminal oxidases implied that, even on the scale of the bacterial cell, spatial effects significantly influence oxygen-sensing. Several transcripts exhibited asymmetrical patterns of abundance in aerobic to anaerobic and anaerobic to aerobic transitions. One of these transcripts, ndh, encodes a major component of the aerobic respiratory chain and is regulated by oxygen-responsive TFs ArcA and FNR. Kinetic modelling indicated that ArcA and FNR behaviour could not explain the ndh transcript profile, leading to the identification of another TF, PdhR, as the source of the asymmetry. Thus, this approach illustrates how systematic examination of regulatory responses in stable and dynamic environments yields new mechanistic insights into adaptive processes.

Authors: , Andrea Ocone, Melanie R Stapleton, Simon Hall, Eleanor W Trotter, , ,

Date Published: 8th Aug 2012

Publication Type: Not specified

Reprogramming of Escherichia coli K-12 metabolism during the initial phase of transition from an anaerobic to a micro-aerobic environment

Abstract (Expand)

Many bacteria undergo transitions between environments with differing O₂ availabilities as part of their natural lifestyles and during biotechnological processes. However, the dynamics of adaptation … when bacteria experience changes in O₂ availability are understudied. The model bacterium and facultative anaerobe Escherichia coli K-12 provides an ideal system for exploring this process.

Authors: Eleanor W Trotter, , Andrea M Hounslow, C Jeremy Craven, Michael P Williamson, , ,

Date Published: 27th Sep 2011

Publication Type: Not specified

TFInfer: a tool for probabilistic inference of transcription factor activities

Abstract (Expand)

SUMMARY: TFInfer is a novel open access, standalone tool for genome-wide inference of transcription factor activities from gene expression data. Based on an earlier MATLAB version, the software has now … been extended in a number of ways. It has been significantly optimised in terms of performance, and it was given novel functionality, by allowing the user to model both time series and data from multiple independent conditions. With a full documentation and intuitive graphical user interface, together with an in-built data base of yeast and Escherichia coli transcription factors, the software does not require any mathematical or computational expertise to be used effectively. AVAILABILITY: http://homepages.inf.ed.ac.uk/gsanguin/TFInfer.html CONTACT: gsanguin@staffmail.ed.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Authors: H M Shahzad Asif, , , Neil D Lawrence, Magnus Rattray,

Date Published: 24th Aug 2010

Publication Type: Not specified

Powered by
 (v.1.16.0-pre)
About FAIRDOMHub | Funding and Programmes | Credits | Terms & Conditions | Imprint | Cookie preferences
Copyright © 2008 - 2024 The University of Manchester and HITS gGmbH