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Project 3: SUMO
Systems Understanding of Microbial Oxygen Responses
The bacterium Escherichia coli is a common inhabitant of the human gut but is also of special interest as a laboratory experimental tool; many decades of study have produced an impressive description of processes essential for life.
However we must now consider how the individual components that make up a biological system work together to produce coherent patterns of behaviour. We have chosen to investigate the responses of E. coli to oxygen availability, because:
- The system is composed of relatively simple modules that participate in complex interactions;
- There is a detailed parts list of the main regulatory systems (genome sequence, participating proteins, molecular mechanisms);
- There are existing published data sets and data from precursor projects that permit the integration of specific and sound mathematical modelling approaches from the very beginning of the project; and
- Powerful techniques for highly controlled and reproducible experiments are available (transcriptomics, facile genetics, chemostat culture);
- The system is biologically, medically and industrially significant.
This systems approach will reveal new insight into the adaptations that occur in response to changes in oxygen availability and offer opportunities for efficient re-engineering for industrial purposes and target-identification for medical applications. We will collectively obtain and analyse, using commonly agreed protocols, highly reproducible transcriptomic, proteomic, metabolomic and biochemical data sets that describe the dynamics of the response to oxygen. Data sets will be integrated to elaborate predictive mathematical and computer science models in an iterative process of model-based hypothesis generation and experimental design.
Specifically, we will investigate how this bacterium senses oxygen, or the associated changes in oxidation/reduction balance, via the Fnr and ArcA proteins, how these systems interact with other regulatory systems, and how the redox response of an E. coli population is generated from the responses of single cells. There are five sub-projects to determine system properties and behaviour and three sub-projects to employ different and complementary modelling approaches using published data sets and data emerging from our own work. We will construct increasingly elaborate models of the system at different levels of detail, which will be used to generate new hypotheses and influence further experimental design.
Project partners:
Robert Poole, University of Sheffield, UK (Project Coordinator)
Jeff Green, University of Sheffield, UK
Joost Teixeira de Mattos, University of Amsterdam, The Netherlands
Katja Bettenbrock, Max-Planck-Institute Magdeburg, Germany
Ernst-Dieter Gilles, Max-Planck-Institute Magdeburg, Germany
Michael Holcombe, University of Sheffield, UK
Thomas Sauter, University of Stuttgart, Germany
Oliver Sawodny, University of Stuttgart, Germany
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