Project Details
TRR 34: Pathophysiology of Staphylococci in the Post-Genome-Era
Subject Area
Medicine
Biology
Biology
Term
from 2006 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 16524344
Staphylococcus aureus is a human pathogen of increasing significance. Because antibiotic resistances are spreading, this bacterium has become a threat to the human race. A better understanding of its infection biology is urgently required to successfully combat the pathogen. In the post-genomic era, the availability of the genome sequences of several strains of S. aureus and also other staphylococcal species provides the basis for a comprehensive understanding of their cell physiology and infection biology as an entity.
The basic concept of this Transregional Collaborative Research Centre initiative is to combine long-standing expertises in Tübingen and Würzburg in cell physiology/biochemistry and infection biology of S. aureus in general with the established expertise in proteomics of Gram-positive bacteria in Greifswald. The unique structure places this consortium in a favourable position to effectively take advantage of the great opportunities offered by the post-genomic era and to achieve a new quality of understanding of the life processes of this pathogen.
The global aims of the three main project areas of the consortium (A, B and C) can be summarised as follows:
(1) to use functional genomics techniques to come to a new understanding of cell physiology as an essential prerequisite for the understanding of infection biology, focussing on two main parts: (1.1.) basic understanding of cell metabolism and stress/starvation responses (project area A); (1.2.) comprehensive analysis of the regulation, function and structure of virulence factors as components of the complex gene expression network (project area B).
(2) to use the great potential of gel-based and gel-free proteomics to investigate new fields of cell physiology of S. aureus (protein targeting and secretion, phosphoproteomics and signal transduction, interactomics, protein damage, proteome-wide proteolysis).
(3) In the first funding period, the physiology of S. aureus and its role in the behaviour of the pathogen in the host are of prime interest. This knowledge will contribute to a better understanding of the host-pathogen interaction (project area C), which will be focussed on in the second funding period.
Finally, all the quantitative "omics" data that are generated under standardised conditions will pave the way towards a systems biology approach to S. aureus.
The basic concept of this Transregional Collaborative Research Centre initiative is to combine long-standing expertises in Tübingen and Würzburg in cell physiology/biochemistry and infection biology of S. aureus in general with the established expertise in proteomics of Gram-positive bacteria in Greifswald. The unique structure places this consortium in a favourable position to effectively take advantage of the great opportunities offered by the post-genomic era and to achieve a new quality of understanding of the life processes of this pathogen.
The global aims of the three main project areas of the consortium (A, B and C) can be summarised as follows:
(1) to use functional genomics techniques to come to a new understanding of cell physiology as an essential prerequisite for the understanding of infection biology, focussing on two main parts: (1.1.) basic understanding of cell metabolism and stress/starvation responses (project area A); (1.2.) comprehensive analysis of the regulation, function and structure of virulence factors as components of the complex gene expression network (project area B).
(2) to use the great potential of gel-based and gel-free proteomics to investigate new fields of cell physiology of S. aureus (protein targeting and secretion, phosphoproteomics and signal transduction, interactomics, protein damage, proteome-wide proteolysis).
(3) In the first funding period, the physiology of S. aureus and its role in the behaviour of the pathogen in the host are of prime interest. This knowledge will contribute to a better understanding of the host-pathogen interaction (project area C), which will be focussed on in the second funding period.
Finally, all the quantitative "omics" data that are generated under standardised conditions will pave the way towards a systems biology approach to S. aureus.
DFG Programme
CRC/Transregios
Completed projects
- A01 - Physiological proteomics of Staphylococcus aureus - from stress physiology to in vivo proteomics (Project Heads Engelmann, Susanne ; Hecker, Michael )
- A02 - Phosphoproteomic analysis of Staphylococcus aureus: Functional characterization of kinases and identification of their substrates (Project Head Ohlsen, Knut )
- A03 - Impact of membrane potential on Staphylococcus aureus biofilms (Project Heads Götz, Friedrich ; Riedel, Katharina )
- A05 - Bioinformatical analysis and metabolic modelling of growth phase-related changes in staphylococci (Project Head Dandekar, Thomas )
- A06 - X-ray analysis of enzymes and virulence factors of pathogenic staphylococci (Project Head Stehle, Thilo )
- A08 - A systems biology perspective of regulatory and metabolic adaptation of Staphylococcus aureus to infection-related conditions (Project Heads Dandekar, Thomas ; Fuchs, Stephan ; Pané-Farré, Jan ; Völker, Uwe )
- B01 - Role of the stringent response in bacterial survival, antibiotic tolerance and cell death (Project Head Wolz, Christiane )
- B02 - Virulence factors in Staphylococcus aureus: Regulation and function (Project Head Engelmann, Susanne )
- B03 - The mechanisms of protein secretion in Staphylococcus aureus (Project Head Antelmann, Haike )
- B04 - Regulation of methionine metabolism in Staphylococci: Impact on fitness and virulence (Project Heads Vogel, Jörg ; Ziebuhr, Wilma )
- B05 - Wall teichoic acid structure variation in Staphylococcus-host interaction (Project Head Peschel, Andreas )
- C02 - Analysis of Staphylococcus aureus-host cell interactions by transcriptomic and proteomic approaches (Project Heads Hacker, Jörg Hinrich ; Völker, Uwe )
- C03 - The analysis of staphylococcal infections by means of new imaging techniques (Project Heads Hacker, Jörg Hinrich ; Szalay, Aladar )
- C04 - Characterization of the immune proteome of Staphylococcus aureus (Project Head Bröker, Barbara )
- C06 - Post-invasion events in Staphylococcus aureus-infected host cells - A combined transcriptomics/proteomics in vivo approach (Project Heads Rudel, Thomas ; Sinha, Bhanu ; Vogel, Jörg ; Völker, Uwe )
- C07 - Staphylococcus aureus in the airways of cystic fibrosis patients, a human model for long-term adaptive interaction (Project Heads Kahl, Barbara C. ; Mellmann, Alexander )
- C08 - The impact of the host glyco-receptor repertoire on staphylococcal tissue specificity (Project Head Weidenmaier, Christopher )
- C10 - Characterizing and deciphering the interaction of platelets and monocytes with Staphylococcus aureus (Project Heads Greinacher, Andreas ; Hammerschmidt, Sven )
- C11 - Host cell death induced by Staphylococcus aureus and its linkage to phagosomal escape (Project Heads Fraunholz, Martin J. ; Rudel, Thomas ; Sinha, Bhanu )
- C12 - Detecting and deciphering Staphylococcus aureus strategies that cause chronic and persistent infections (Project Heads Löffler, Bettina ; Peters, Georg ; Roth, Johannes )
- C13 - Molecular interactions of Staphylococcus aureus with professional phagocytes (Project Heads Barczyk-Kahlert, Ph.D., Katarzyna ; Roth, Johannes )
- C14 - In vivo investigation of the role of adhesins in Staphylococcus aureus-induced infective endocarditis and development of a diagnostic imaging marker (Project Heads Faber, Cornelius ; Hörr, Verena ; Löffler, Bettina )
- C15 - Differential activation of formyl peptide receptors by Staphylococcus aureus and consequences for inflammation (Project Head Kretschmer, Dorothee )
- C16 - Host-pathogen interaction of Staphylococcus aureus - insight from a population-based perspective (Project Heads Bröker, Barbara ; Völker, Uwe )
- INFZ01 - An integrated view on adaptation of Staphylococcus aureus (Project Heads Bernhardt, Jörg ; Dandekar, Thomas ; Mäder, Ulrike )
- V - headquarters and administration (Project Heads Bröker, Barbara ; Hecker, Michael ; Peschel, Andreas )
- Z02 - Proteomics of Staphylococcus aureus (Project Heads Becher, Dörte ; Hecker, Michael ; Riedel, Katharina )
- Z03 - In vivo imaging of Staphylococcus aureus infections (Project Heads Faber, Cornelius ; Ohlsen, Knut )
- Z04 - Metabolomics of Staphylococcus aureus (Project Head Lalk, Michael )
Applicant Institution
Universität Greifswald
Co-Applicant Institution
Eberhard Karls Universität Tübingen; Julius-Maximilians-Universität Würzburg; Universität Münster
Spokespersons
Professorin Dr. Barbara Bröker, since 5/2013; Professor Dr. Michael Hecker, until 4/2013