Centre for Biological Signalling Studies bioss from Analysis to Synthesis Area D1 Pathway assembler

Description of the project:
The BIOSS initiative will generate high-throughput data using novel technology that will be harnessed by BIOSS researchers via high quality experiments. High-throughput experiments require bioinformatics analysis afterwards, for the interpretation of the vast amounts of data that are produced – rigorous analysis, incorporating and respecting biological detail, is an absolute must. High-quality experiments in contrast require bioinformatics both for planning the experiment due to the combinatorial behavior of possible interactions (see Figure 1), as well as for analysis of the results after the experiment. Thus, bioinformatics has an important role to play in BIOSS in general, and project D1 – the BIOSS pathway assembler – in particular. The proposed Bioinformatics contributions to the BIOSS Pathway Assembler are: Prediction of the important players in signalling cascades. In-silico evaluation of signalling models. Design of key experiments, design of mutants/new fusion proteins The iterative refinement of models and experiments, since experiments lead to better models, which enable further well directed experiments. Analysis of the functional effects of the predicted and observed interactions. We will focus on ITAM-based signalling, and in particular on interactions between ITAM motifs and SH2 domains, with the SH2 domains of Syk and SHIP1 as our main example applications. Contrary to the earlier perception that negative regulators interact only with inhibitory motifs (ITIMs), it is now an emerging truth that reality is much more complex – for example, in spite of their very different functions, Syk and SHIP1 bind the same ITAM. Similarly, in addition to the established model of ITAMs and ITIMs “duelling” for the control of cellular activation within the immune system, it has been shown that ITAM-bearing receptors can also inhibit immune response (Hamerman and Lanier, 2006).

Additional information: http://www.bioss.uni-freiburg.de
contact person: Kousik Kundu
Email: kousik@informatik.uni-freiburg.de
Start of project: 2008
End of project: 2011
Project Management:
Albert-Ludwigs-University Freiburg
Prof. Dr. Rolf Backofen
Prof. Dr. Rolf Backofen
Georges-Köhler-Allee 106
79110 Freiburg

Phone: +49 (0) 761-203-7461
Fax: +49 (0) 761-203-7462
Email: backofen@informatik.uni-freiburg.de
Actual Research Report
  • DFG