Changes between Version 26 and Version 27 of public


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Timestamp:
Apr 28, 2011, 11:23:27 AM (13 years ago)
Author:
stagge
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    v26 v27  
    88=== About SUMO ===
    99==== General Information ====
    10 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.
    1110
    12 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:
     11The 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.
     12However 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 varying conditions  (e.g. oxygen availability, alternative electron acceptors and different carbon sources), because:
    1313
    14    1. The system is composed of relatively simple modules that participate in complex interactions;
    15    2. There is a detailed parts list of the main regulatory systems (genome sequence, participating proteins, molecular mechanisms);
    16    3. 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
    17    4. Powerful techniques for highly controlled and reproducible experiments are available (transcriptomics, facile genetics, chemostat culture);
    18    5. The system is biologically, medically and industrially significant.
     14   1.   The system is composed of relatively simple modules that participate in complex interactions;
     15   2.   There is a detailed parts list of the main regulatory systems (genome sequence, participating proteins, molecular mechanisms);
     16   3.   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
     17   4.   Powerful techniques for highly controlled and reproducible experiments are available (transcriptomics, facile genetics, chemostat culture);
     18   5.   The system is biologically, medically and industrially significant.
    1919
    20 This systems approach reveals 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 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 are integrated to elaborate predictive mathematical and computer science models in an iterative process of model-based hypothesis generation and experimental design.
     20==== SUMO,,1,, ====
    2121
    22 Specifically, we 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 construct increasingly elaborate models of the system at different levels of detail, which are used to generate new hypotheses and influence further experimental design.
     22This project first started out in 2007 named SUMO (Systems understanding of Microbial oxygen responses) and was founded by the European research initiative !SysMo ([http://www.sysmo.net SysMo]). During the first 3years of founding we used a multiple systems level approach to broaden our knowledge about the metabolic adaption that occurs in response to changes in oxygen availability. Especially the application of commonly agreed protocols which led to highly reproducible transcriptomic, proteomic, metabolomic and biochemical data sets helped to describe the dynamics of ''E.colis'' response to oxygen. Specifically, we investigated 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. Furthermore these data sets of high quality have been implemented into mathematical models and computer science models of various types (e.g. ODE- and Agent-based modeling). This allowed us to set up new model-based hypothesis and additionally on this basis new experiments have been designed to help validate our models and extend our knowledge about metabolism.
     23
     24==== SUMO,,2,, ====
     25
     26In 2011 we kindly received another funding from the !SysMo-initiative. Here in SUMO,,2,, our aim is to extend our SUMO,,1,, project work to obtain a complete, quantitative description of the integrated catabolic subsystems of ''E. coli'', from regulation to energy conservation. To achieve this goal, SUMO,,2,, will build upon the progress made in SUMO by extending our systematic analysis of ''E. coli'' catabolism into three new thematic areas:
     27
     28   1.   System dynamics during transition to anaerobic respiration and in response to pulses of electron acceptors
     29   2.   Adaptive responses to different catabolic modes
     30   3.   Multi-scale and multi-level modelling of catabolism
     31
     32Under these broad headings, we will collect fully compatible datasets at molecular, single-cell and population levels and assemble these into multi-scale complementary models that build upon those already created in SUMO. Our workplan embraces a virtuous cycle of iterative experiments and modelling, in which models guide the experimental work; this will enable us to realise our ultimate goal, which is a coherent model of catabolism.
     33
    2334
    2435==== People of SUMO,,2,, ====
    … …  
    3142==== Publications ====
    3243(related to SUMO and SUMO,,2,,, which acknowledge the support by SysMO)
    33  * Bekker M., de Vries, S., Ter Beek, A., Hellingwerf, K. and Teixeira de Mattos, M. (2009). Non-electrogenic respiration by Escherichia coli: the quinol oxidase cytochrome bd-II does not contribute to oxidative phosphorylation, submitted.
     44 * Bekker M., de Vries, S., Ter Beek, A., Hellingwerf, K. and Teixeira de Mattos, M. (2009). Non-electrogenic respiration by ''Escherichia coli'': the quinol oxidase cytochrome bd-II does not contribute to oxidative phosphorylation, submitted.
    3445 * Green, J., Crack, J.C., Thomson, A.J. and Le Brun, N.E. (2009) Bacterial sensors of oxygen. Current Opinions in Microbiology 12, 145-151.
    3546 * Jervis, A.J., Crack, J.C., White, G., Artymiuk, P.J., Cheesman, M.R., Thomson, A.J., Le Brun, N. and Green, J. (2009) The O2 sensitivity of the transcription factor FNR is controlled by Ser24 modulating the kinetics of the [4Fe-4S] to [2Fe-2S] cluster conversion. Proceeding of the National Academy of Sciences USA 106, 4659-4664.
    36  * Maleki-Dizaji, S., Holcombe, M., Rolfe, M.D., Fisher, P., Green, J., Poole, R.K., Graham, A.I. and SysMO-SUMO consortium. (2009) A systematic approach to understanding Escherichia coli responses to oxygen: from microarray raw data to pathways and published abstracts. Online Journal of Bioinformatics 10, 51-59.
    37  * Shepherd, M., Sanguinetti, G., Cook, G.M. and Poole, R.K. (2009) The AppBC quinol oxidase (cytochrome bd-II) of Escherichia coli: up-regulation in a cytochrome bd-I mutant in concert with acid resistance genes, submitted.
    38  * Steinsiek S, Frixel S, Stagge S; SUMO, Bettenbrock K. (2011) Characterization of E. coli MG1655 and frdA and sdhC mutants at various aerobiosis levels, J Biotechnol. [Epub ahead of print]
     47 * Maleki-Dizaji, S., Holcombe, M., Rolfe, M.D., Fisher, P., Green, J., Poole, R.K., Graham, A.I. and SysMO-SUMO consortium. (2009) A systematic approach to understanding ''Escherichia coli'' responses to oxygen: from microarray raw data to pathways and published abstracts. Online Journal of Bioinformatics 10, 51-59.
     48 * Shepherd, M., Sanguinetti, G., Cook, G.M. and Poole, R.K. (2009) The AppBC quinol oxidase (cytochrome bd-II) of ''Escherichia coli'': up-regulation in a cytochrome bd-I mutant in concert with acid resistance genes, submitted.
     49 * Steinsiek S, Frixel S, Stagge S; SUMO, Bettenbrock K. (2011) Characterization of ''E. coli'' MG1655 and frdA and sdhC mutants at various Aerobiosis levels, J Biotechnol. [Epub ahead of print]
    3950
    4051=== Contact ===