Das Ras-Protein auf verschiedenen Skalen

News

24.11.2017

Science-article published:

Prof. Dr. Klaus Gerwert
Prof. Dr. Klaus Gerwert
Head of Department

Mission

At the Department of Biophysics, we investigate protein dynamics at different scales. The understanding of protein dynamics is not only of academic interest in basic research, but also has a great application potential in medicine. Disorders of protein dynamics can cause serious diseases. Almost all types of cancer and neurodegenerative diseases are triggered by oncogenic mutations or misfolding of proteins. Hence, these protein modifications are suitable biomarkers for the early detection of cancer or neurodegenerative diseases on the one hand. On the other hand, the modified proteins are targets for drugs in precision medicine.

Example Ras protein

In the scheme above, the Ras protein is exemplarily shown at different scales. It transmits external growth signals to the nucleus. Oncogenic mutations within the GTP-binding pocket of the Ras protein lead to a disturbance of the switch-off function so that Ras constantly stimulates the growth signal transduction and thereby induces uncontrolled growth signals in the nucleus. The permanent activation of the growth signal transduction pathway ultimately leads to an uncontrolled cell growth, so that in the long term tumors develop in the cell cluster, namely the tissue. Oncogenically mutated Ras protein is present many tumors.

Methodical approach

To study protein dynamics at atomic level, a wide range of biochemical and molecular biological methods are orchestrated with molecularly resolving biophysical methods. In particular, our newly developed methods for label-free time-resolved infrared difference spectroscopy are applied on recombinant proteins. The experimental results are evaluated with biomolecular simulations. This approach eventually yields molecular reaction mechanisms of proteins with highest spatial and temporal resolution. Not only static images of the protein ground state but movies of the protein function are created. For example, this approach was used to elucidate the molecular reaction mechanisms of bacteriorhodopsin and the Ras protein.
Furthermore, (body) fluids are measured using the ATR technology. Especially misfoldings of protein biomarkers are determined that are bound to the functionalized surface of the ATR crystal. Based on the ATR technology, for example, an immunosensor was developed for the early detection of Alzheimer's disease in blood samples.
Living cells are analyzed in a label-free manner using Raman and CARS imaging. In particular, the effect of drugs (Companion diagnostics) on the cell function is represented with spatial distribution of the active substances.
Tissue is classified by label-free FTIR imaging. In particular, tumor tissue is characterized in an automated and label-free differential diagnostic way. Finally, protein biomarkers can be identified by combination with molecularly resolving proteomic analysis.

Third-party funding and cooperation partners

Most of the work is third-party funded (DFG, BMBF, EU) and is mainly carried out within the framework of large consortia. The basic scientific research is carried out in SFB 642 (spokesman K. Gerwert) and the translationally and clinically oriented research within PURE (spokesman K. Gerwert). The department has national and international cooperation partners, in particular the ISAS and the Max Planck Institute for Molecular Physiology in Dortmund as well as the SIBS in Shanghai.

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