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Michael Boutros – from the study of social gene networks to the management of the DKFZ

Deregulation of cell signalling pathways is a major driver of cancer. Prof. Dr. Michael Boutros has pioneered the development of new methods for the analysis of genetic interactions in such complex networks. He has been acting Chairman and Scientific Member of the Management Board of the German Cancer Research Center (DKFZ) since September 1st 2015.

Prof. Dr. Michael Boutros © DKFZ

It came as a big surprise when it was announced that Michael Boutros had become acting Chairman and Scientific Member of the Management Board of the German Cancer Research Center (DKFZ) from September 1st 2015. He temporarily succeeds Professor Otmar D. Wiestler, who became President of the Helmholtz Association in Berlin on September 1st. In early July, the German Federal Ministry of Research and Education announced that the Heidelberg neurooncologist Professor Wolfgang Wink would be head of the DKFZ. However, just eleven days later the DKFZ put out a further announcement to the effect that Wink would not be taking on the post.

Michael Boutros was born in Bochum in 1970; he studied biology and biochemistry at the Universities of Aachen, Witten/Herdecke and New York, going on to do his PhD at the European Molecular Biology Laboratory (EMBL) in Heidelberg and the University of Heidelberg. He then worked as a post-doc at Harvard Medical School before joining the DKFZ in 2003 where he created the Boveri junior research group Signalling and Functional Genomics with the support of the DFG's Emmy Noether programme. Since 2008, he has been a professor at the University of Heidelberg and departmental head at the DKFZ. In 2007, he received the Johann Zimmermann Cancer Research Award and he has been an elected member of the European Molecular Biology Organisation (EMBO) since 2013.

His original, internationally acclaimed research was, inter alia, funded by a highly prestigious European Research Council Advanced Grant. He gained the qualifications necessary for his current role at an early stage. During his post-doc period in the USA, he was awarded a Master in Public Administration from the Harvard Kennedy School and later studied in the Helmholtz Association's Leadership Academy. Boutros' major research topic – the positive and negative interactions of genes – is also similar in some ways to his current challenge of managing an institution with over a thousand scientists.

Analysis of genetic interaction networks

Analysis of a genetic interaction network. Proteins (coloured circles) are present as complexes or close cooperation units; directed interactions between proteins or protein groups are highlighted with arrows. © EMBL/DKFZ

Michael Boutros and his team in the Division of Signalling and Functional Genomics at the DKFZ in Heidelberg are studying signalling pathways that control the development of organisms and the onset of cancer. These include, for example, Wnt signalling pathways which, when deregulated, can lead to colon, and possibly also other types of cancer. Boutros and his team have made significant contributions to the molecular understanding of these signalling pathways. Genes work together in complex genetic networks, and the analysis of these networks is an enormous challenge. Genes are as sociable as humans who work together as social beings in teams, companies and organisations, where our productivity is not the same as when we work alone. For example, when two mutated genes interact in a network, phenotypic effects are observed that do not occur when only one of the two genes is altered.

Boutros and his colleagues used an innovative high-throughput screening approach for analysing genetic interactions. It enabled a genome-wide identification of genes using RNA interference (RNAi) and meant that the researchers could specifically silence particular genes. By combining this combinatorial RNAi technique with automated single-cell phenotyping, the researchers were able to map directed genetic interactions on the large scale in Drosophila cells. They selected a total of 1,367 genes from these RNAi experiments and studied the ones that they believed had an important function in the social network of genes.

Each of the 1,367 genes was silenced in combination with any one of 72 key genes that were identified as likely hubs in the genes' social networks, and the resulting phenotype was determined using automated microscopic imaging of the individual cells. The researchers used multivariate statistics (when several properties are analysed simultaneously to determine the direction of genetic interactions – i.e., whether gene A influenced gene B, or vice versa). They were also able to show whether the interactions reinforced or weakened the effects. These genetic interactions could potentially be used to identify signalling pathways involved in cell division and successive protein activities.

Research into signalling pathways helps to understand cancers

Main building of the German Cancer Research Center in Heidelberg, the largest biomedical research institution in Germany. © DKFZ

The research was conducted in cooperation with Wolfgang Huber from the EMBL and published in the online journal eLife. Huber is an expert in statistical physics. The approach for analysing genetic alterations and their effects at specific points in time in regulatory networks is important not only for basic research, but also for cancer research. The scientists have already been able to show that the Ras signalling pathway, which plays an important role in the control of cell growth, interacts with the SWI/SNF chromatin remodelling complex, which itself is instrumental for the packaging of nuclear DNA in nucleosomes. This interaction is also found in human cancer cells.

The mapping of genetic interactions can be used to identify new targets for anticancer drugs. According to Boutros, this kind of mapping might also contribute to clarifying why tumours become resistant to anticancer drugs. Research in the Division of Signalling and Functional Genomics will go ahead even though the director will henceforth have limited time for his team because of his new function as the head of Germany's largest biomedical research institution. However, most of his colleagues believe he will return to the laboratory once a new chairman has been appointed.

Original paper:

Fischer B, Sandmann T, Horn T, Billmann M, Chaudhary V, Huber W, Boutros M: A map of directional genetic interactions in a metazoan cell. eLife 2015, DOI: 10.7554/eLife.05464

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/michael-boutros-from-the-study-of-social-gene-networks-to-the-management-of-the-dkfz