uni'wissen 01-2016_ENG

biology for the study: They built a molecular switch into tumor cells with the BRAFV600E gene, enabling it to switch off the assembly instruc- tions for the mutated B-RafV600E protein. “But our results only apply to cell cultures. This principle cannot yet be applied to humans. However, such experiments can help to improve therapies with the existing B-Raf inhibitors.” A New Weak Spot Brummer and his team have also discovered a possible weak spot that could be targeted to eliminate several mutations unrelated to V600E. The researchers introduce a so-called AVKA mutation to the gene. It causes the lips of B-Raf’s mouth to remain closed, making it much more difficult to activate. This approach could serve as an alternative to the existing B-Raf inhibitors, which are only approved for V600E or V600K mutations. “Our results show that the AVKA mu- tation is effective at blocking B-Raf and hardly has any side effects at all.” Brummer hopes that Further Reading Köhler, M. / Röring, M. / Schorch, B. et al. (2016): Activation loop phosphorylation regulates B-Raf in vivo and transformation by B-Raf mutants. In: The EMBO Journal 35/2, pp. 143–161. doi: 10.15252/ embj.201592097 Herr, R. / Kohler, M. / Andrlova, H. et al. (2015): ): B-Raf inhibitors induce epithelial differentiation in BRAF-mutant colorectal cancer cells. In: Cancer Research 75/1, pp. 216–229. doi: 10.1158/0008- 5472.CAN-13-3686 Kordes, M. / Roring, M. / Heining, C. et al. (2015): Cooperation of BRAFF595L and mutant HRAS in histiocytic sarcoma provides new insights into oncogenic BRAF signaling. In: Leukemia advance online publication. doi: 10.1038/leu.2015.319 Dr. Tilman Brummer studied biology in Freiburg and wrote his dissertation at the former Max Planck Institute of Immunobiology. In 2003 he accepted a posi- tion at the Garvan Institute of Medical Research in Sydney, Australia, and in 2008 he came to Freiburg’s Cluster of Excellence BIOSS Centre for Biological Signalling Studies on a grant from the German Research Founda- tion’s Emmy Noether Program. He leads a research group at the Institute of Molecular Medicine and Cell Research and is also a principle inves- tigator at the Spemann Graduate School of Biology and Medicine (SGBM) and collaborative research center 850, “Control of Cell Motility in Morphogenesis, Cancer Invasion, and Metastasis,” at the University of Freiburg. In 2015 he was appointed to a Heisenberg Professorship by the German Research Foundation. His research focuses on signaling in cells, especially cancer cells. Photo: Klaus Polkowski/BIOSS the discovery of this weak spot will lead one day to an active substance for treating cancer. “We are continuing to investigate the consequences of this mutation for the regulation of B-Raf.” As a biologist, Brummer is interested in funda- mental research. However, he doesn’t believe in separating medicine and biology: “There’s a lot to be learned about biological mechanisms from the study of diseases, and doctors can also profit from fundamental research” – as in the case of the 35-year-old patient with the BRAFF595L muta- tion. Brummer and his team discovered that this rare mutation sends out signals that can cause cancer. However, the man died before an appro- priate therapy could be found. Nevertheless, the researchers gained new insight that can help the next time a patient is diagnosed with a tumor with this BRAF mutation. www.mol-med.uni-freiburg.de/mom/brummer One of these petri dishes contains cells with the normal BRAF gene as a control, and the other contains the same cells with a BRAFF595L mutation. The cells in the control dish (left) stop growing as soon as they make contact with their neighbors. They thus appear “colorless” here. The cells with the BRAFF595L mutation (right) grow uncontrollably over one another – the blue-colored cell clusters are visible with the naked eye. Photo: Sandra Braun/Tilman Brummer 11

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