TP5 - InCa

Chemical Modulation of Kinases (CheMoKine) to Unravel Their Functional Role in Cancer, Metabolism and Inflammation

The lifestyle and environmental factors of a person has a great influence on the development of mutations within the genome and thus significantly influences the development of cancer. While some risk factors such as cigarette smoke are widely known today, other processes such as chronic inflammatory processes, obesity, and exposure to certain pathogens are less well-established. In addition to the importance of these factors for the development of tumors, the interaction of tumor cells with immune, inflammatory and other cells in their environment is also of great importance for cancer development and tumor growth.

While great progress has been made in directly addressing processes and proteins within the cancer cells in recent years, the processes of the interaction of tumor cells with their environment have so far been poorly understood and are therefore rarely used in therapies. The aim of this project is to further elucidate the molecular basis of the interactions and to determine the potential for new therapeutic approaches.

Daniel Rauh's research group will focus on the structure-based development of small-molecule probes that perturb and influence individual proteins in this complex network. For this purpose, a platform called RASPELD (Robotics-Assisted Screening Platform for Efficient Ligand Discovery; see figure) was developed, which enables the efficient development of such probes and is made available to the consortium.

RASPELD – A Robotics‐Assisted Screening Platform for Efficient Ligand Discovery 1. The iterative process of ligand development consists of the (I) substance library of the Rauh group, (II) the automated handling of the substances, (III) various assay technologies for characterizing the substances, (IV) an intensive characterization and validation of hits found using biochemical and structural biological methods and (V) organic synthesis to generate improved derivatives. An integrated database (VI) enables efficient storage and access to all data collected.