Computational proteomics for quantitative characterization of post-translational modification-dependent protein-protein interaction networks

• Applicant: Dr. Marc Kirchner
• Subject Area: Bioinformatics and Theoretical Biology
• Term: Funded in 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 131030115

Systems biology attempts to build models of biochemical interactions that drive biological processes such as cell growth, proliferation and death. Current modeling approaches are based on gene expression and bait-prey protein experiments. The resulting datasets fail to deliver information on the state of post-translational modification (PTM) of proteins of interest. It is well known that PTMs play crucial roles in many cellular pathways and that differentially modified forms of the same protein may exhibit significant difference in their biochemical interaction behavior and kinetics. Although PTMs can be monitored using mass spectrometry techniques, such information has not yet been included in the PPI network modeling processes. This grant proposal addresses the development of computational approaches for the characterization of PPI networks based on quantitative mass spectrometry experiments, which, for the first time, incorporate protein PTM information into the PPI network inference procedure. The proposed workflow will be applied to time-series analysis of post-translational modification in relation to substrate specificity of the anaphase promoting complex (APC). The results acquired with the proposed analytical methodology will yield a better understanding of the switch-like functionality PTMs exhibit and provide a key to highly specific, tailored drug and medical treatment development.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Hanno Steen, Ph.D.