Dissection of oncogene dependencies by small organic molecule perturbations

Coordinator:		Dr. Daniel Rauh                                                                                Prof. Dr. Herbert Waldmann
Institution:		MPI Dortmund, Chemical Genomics Centre der Max Planck Gesellschaft   MPI Dortmund
Homepage:		www.mpi-dortmund.mpg.de

The overall goal of this subproject is the identification of oncogenic signaling pathway dependencies by performing perturbation experiments with small organic molecules on cellular systems. 

Within the interdisciplinary environment of this initiative, our new multifaceted approach will not only lead to a better understanding of the molecular and cellular causes of fatal diseases but also foster detailed understanding of inhibitory principles that might represent starting points for future drug discovery. We envision achieving these goals by screening in-house compound libraries for modulation of mutated oncogenes in cellular systems and by structure based design and synthesis of small organic molecules to probe functions of mutated oncogenes in cellular and in in-vitro systems. We will design, synthesize and use fluorescent functional probes to investigate the spatial and temporal distribution of mutated human oncogenes in living cells and use structural biology to better understand drug resistance mutations in oncogenes.







Figure legend:
How do proteins function? A library of small molecules is screened using cell assays to identify one with interesting biological activity. Pull-down experiments and mass spectrometry analysis help to identify target proteins associated with the observed phenotypes. Structural biology and the understanding of protein ligand interactions assist in the design and synthesis of molecular probes – such as fluorescent reporters – to dissect protein function at the cellular level.