
Victor Sourjik
Group Leader in the
DKFZ-ZMBH Alliance
ZMBH, Im Neuenheimer Feld 282
69120 Heidelberg, Germany
Tel.: + 49-6221 54 6858
Fax.: +49-6221 54 5892
sourjik.victor@zmbh.uni-heidelberg.de
V. Sourjik's Annual Report
Welcome to the Sourjik Lab! Most signalling functions in a cell are executed by protein networks rather than by single proteins. Although specific molecular mechanisms differ, any such system must be able to extract weak signals from a noisy environment, adapt to background perturbations, and integrate and discriminate multiple cues. Elucidating network features that enable efficient signal processing requires a combination of the quantitative in-vivo experiments and detailed computer modelling. Microbial networks are excellent model systems for such analyses because of their relatively simple topology and well studied genetics and biochemistry. Levels and intercellular distribution of CheY-YFP (green) and FliM-CFP (red), expressed from native chromosomal positions. FliM labels functional and assembling flagellar motors; CheY labels polar and lateral clusters of the sensory complexes. In longer cells, lateral clusters are positioned at one of the future division sites. The expression levels of CheY show a large intercellular variation, or gene expression noise. Image by L. Løvdok.
Quantitative analyses of microbial networks
Our research to date mainly focused on chemotaxis in Escherichia coli as a model signalling system. We use a range of fluorescence microscopy techniques to map intracellular localization and interactions of all chemotaxis proteins, and to investigate assembly and dynamics of higher-order signal processing complexes. We further analyze robustness of the chemotaxis network against such common perturbation as stochastic variations in protein levels. In collaboration with several computer modelling groups, we use these data for a detailed quantitative description of the network in silico. With the model at hand, we are able to rationalize different properties of the network, and explain why the observed network was evolutionary selected.
To test generality of our conclusions about robust design and evolutionary optimality of the chemotaxis network, we now extend a combination of fluorescence microscopy studies and computer modelling to analyze several other model microbial networks. In E. coli, we focus on the sugar uptake systems and their cross-talk with the chemotaxis; the network of two-component sensors; the septum-positioning Min system; and the heat shock response. In the budding yeast S. cerevisiae, we investigate the MAP kinase network. We believe that understanding evolutionary design of these microbial networks will provide guide to future detailed studies of much more complex networks in higher eukaryotes.
Selected Publications
Oleksiuk, O., Jakovljevic, V., Vladimirov, N., Carvalho, R., Paster, E., Ryu, WS., Meir, Y., Wingreen, NS., Kollmann, M. and Sourjik, V. (2011) Thermal robustness of signaling in bacterial chemotaxis. Cell 145: 312-321.
Di Ventura, B. and Sourjik, V. (2011) Self-organized partitioning of dynamically localized proteins in bacterial cell division. Mol. Syst. Biol. 7: 457.
Neumann S, Hansen CH, Wingreen NS, Sourjik V. (2010) Differences in signalling by directly and indirectly binding ligands in bacterial chemotaxis. EMBO J. 29(20): 3484-95.
Boehm A, Kaiser M, Li H, Spangler C, Kasper CA, Ackermann M, Kaever V, Sourjik V, Roth V, Jenal U. (2010) Second messenger-mediated adjustment of bacterial swimming velocity. Cell 141(1):107-16.
Løvdok, L., Bentele, K., Vladimirov, N., Müller, A., Pop, F.S., Lebiedz, D., Kollmann, M., Sourjik, V. (2009) Role of translational coupling in robustness of bacterial chemotaxis pathway.. PLoS Biol.7:e1000171.
Kentner D, Sourjik V. (2009) Dynamic map of protein interactions in the Escherichia coli chemotaxis pathway. Mol. Syst. Biol. (2009) 5:238.
Schulmeister, S., Ruttorf, M., Thiem, S., Kentner, D., Lebiedz, D. and Sourjik, V. (2008) Protein exchange dynamics at chemoreceptor clusters in Escherichia coli. Proc. Natl. Acad. Sci. USA 105:6403-6408.
Thiem, S., Kentner, D. and Sourjik, V. (2007) Positioning of chemosensory clusters in E. coli and its relation to cell division. EMBO J., 26: 1615-1623.
Kollmann, M., Løvdok, L., Bartholome, K., Timmer, J. and Sourjik, V. (2005) Design principles of a bacterial signalling network. Nature, 438: 504-507.
Sourjik, V. and Berg, H. C. (2004) Functional interactions between receptors in bacterial chemotaxis. Nature, 428: 437-441.
Reviews
Sourjik, V. and Armitage, J.P. (2010) Spatial organization in bacterial chemotaxis. EMBO J. 29:2724-2733.
Kentner, D., Sourjik, V. (2010) Use of fluorescence microscopy to study intracellular signaling in bacteria. Annu. Rev. Microbiol.64:373-390. Epub 2010 Jun 7.
Sourjik, V. and Wingreen, N.S (2007) Turning to the cold. Nat. Cell Biol. 9: 1029-1031.
Kollmann, M. and Sourjik, V. (2007) In silico biology: from simulation to understanding Curr. Biol. 17: R132-R134.
Sourjik, V. (2004) Receptor clustering and signal processing in E. coli chemotaxis. Trends Microbiol., 12: 569-576.
