Forschungsbericht 2017



e:biofilm - Neue Wirkstoffe gegen Biofilme von Streptokokken (BMBF Verbundprojekt e:Bio-Modul II)

Institut: V-1
Projektleitung: An-Ping Zeng
Stellvertretende Projektleitung: Wei Wang
Mitarbeiter/innen: Anna Gorte
Wael Sabra
Lifu Song
Wei Wang
Laufzeit: 01.06.2014 — 31.05.2017
Finanzierung:Bundesministerium für Bildung und Forschung (BMBF)
Kooperationen:Prof. Dr. Irene Wagner-Döbler, Helmholtz-Zentrum für Infektionsforschung, Braunschweig
Prof. Dr. Andreas Kremling, TU München
Prof. Dr. Christian Apel, RWTH Aachen
Prof. Dr. Georg Conrads, RWTH Aachen
Prof. Dr. Rolf Müller, Helmholtz Institute of Pharmaceutical Research, Saarbrücken
Prof. Dr. Stefan Schulz, TU Braunschweig
VOCO GmbH, Dr. Maletz, Dr. Berg, Cuxhaven
Verbundprojekte: Bundesministerien

As the follow-up project of BioInsys, in this joint BMBF research project, a systems biology approach was used to (1) develop the biofilm inhibitor carolacton towards dental products (e.g. tooth fillings) and (2) transfer the understanding of carolacton action from Streptococcus mutans to other bacteria of the genus Streptococcus, for example, Streptococcus pneumoniae. At IBB/TUHH we worked on the “Top-Down Systems Biology of Streptococci” which covers three work packages: WP1 - Data integration and management; WP2 -Standardized cultivation systems, dynamics data generation and network modeling; WP7 - Proteomic analysis and modelling of regulatory network. WP1 serves as a bioinformatics platform for managing and exploiting genome sequences as well as functional genomic data generated in the consortium for selected Streptococcus strains to be studied in this project. The aim of WP2 is the establishment of fully controlled and standardized cultivation systems of selected Streptococcus strains, and especially for the dynamic studies of the effect of carolacton on these strains. It covers also targeted metabolomic analysis and the reconstruction of carolacton-responsive metabolic networks of the strains studied. In WP7 proteomic/phosphoproteomic analysis will be applied to study the effect of carolacton at protein level, especially the signal transduction pathways affected by carolacton. WP7 is also responsible for the reconstruction of carolacton-responsive regulatory networks using transcriptomics data from the project partner so as to predict key genes/regulators responsive to carolacton treatment.

Stichworte

  • Systems biology, biofilm, streptococci, carolacton, metabolomics, proteomics, phosphoproteomics, bioinformatics, metabolic network, gene regulatory network, reverse engineering, top-down modeling

Publikationen

  • Song, L and Sudhakar, P and Wang, W and Conrads, G and Brock, A and Sun, J and Wagner-Dobler, I and Zeng, A P: A genome-wide study of two-component signal transduction systems in eight newly sequenced mutans streptococci strains. BMC Genomics, 13: S. 128, 2012. , DOI: 10.1186/1471-2164-13-128
  • Georg Conrads, Hans de Soet, Lifu Song, Karsten Henne, Helena Sztajer, Irene Wagner-Döbler and An-Ping Zeng : Comparing the cariogenic species Streptococcus sobrinus and S. mutans on whole genome level. JOURNAL OF ORAL MICROBIOLOGY, 6: S. 26189, 2014. , DOI: 10.3402/jom.v6.26189
  • Sudhakar, P and Reck, M and Wang, W and He, F Q and Wagner-Döbler, I W and Zeng, A P: Construction and verification of the transcriptional regulatory response network of Streptococcus mutans upon treatment with the biofilm inhibitor carolacton. BMC Genomics, 15: S. 362, 2013. , DOI: 10.1186/1471-2164-15-362
  • Lifu Song and An-Ping Zeng: Engineering cells as robots for parallel and highly sensitive screening of biomolecules under in vivo conditions. Sci. Report, 7(15145), 2017.
  • Song, L and Wang, W and Conrads, G and Rheinberg, A and Sztajer, H and Reck, M and Wagner-Dobler, I and Zeng, A P: Genetic variability of mutans streptococci revealed by wide whole-genome sequencing. BMC Genomics, 14: S. 430, 2013. , DOI: 10.1186/1471-2164-14-430
  • Xue, X and Li, J and Wang, W and Sztajer, H and Wagner-Döbler, I: The global impact of the delta subunit RpoE of the RNA polymerase on the proteome of Streptococcus mutans.. Microbiology (Reading, England), 158(Pt 1): S. 191--206, jan 2012. , DOI: 10.1099/mic.0.047936-0, http://www.ncbi.nlm.nih.gov/pubmed/21998164
  • Li, J and Wang, W and Wang, Y and Zeng, A P: Two-dimensional gel-based proteomic of the caries causative bacterium Streptococcus mutans UA159 and insight into the inhibitory effect of carolacton. Proteomics, 13(23-24): S. 3470--3477, 2013. , DOI: 10.1002/pmic.201300077