“This is a very special day for us,” said Professor Martin Lohse, Scientific Director of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), as he opened the eleventh Berlin Late Summer Meeting on October 25, 2018. He added that the conference, which brought together more than 400 systems biologists from all over the world, “marks the beginning of a new chapter for the MDC.”
The three-day conference, according to Lohse, marks not only the anniversary of the Berlin Institute for Medical Systems Biology (BIMSB), the MDC’s systems biology unit that Professor Nikolaus Rajewsky founded ten years ago, but also the imminent opening of a new location of the research center in the heart of the German capital. BIMSB will relocate to the new facility in the coming year. The institute’s successful development, according to Lohse, was predicted with remarkable foresight by Rajewsky, the founder of BIMSB, in his original concept paper.
Well connected to Berlin partners
This is in no small part due to the dedication with which Rajewsky has committed himself to this undertaking, added Professor Peter Frensch, Vice President for Research at Humboldt-Universität zu Berlin, on whose historic grounds the facility is being built. Frensch called BIMSB “a unique species that’s moving to our home turf,” right in the midst of Berlin’s universities and research institutions in the city’s center.
One of these institutions is Charité ‒ Universitätsmedizin Berlin, which for many years has been an important partner of the MDC and BIMSB. Karl Max Einhäupl, Chairman of the Board of Directors of the teaching and research hospital, extolled the physical proximity of the new location, calling it a key to success. He added that the technologies used by BIMSB and the topics it investigates are pioneering new paths in translational medicine, a field to which Charité and the MDC are fully committed.
Wet and dry labs, side by side
Understanding the molecular mechanisms that underlie disease and health has always been the mandate and mission of the MDC. “From a systems biology perspective,” said Rajewsky, “that means pursuing the path from gene to trait, including the many cellular programs and steering mechanisms that interact on multiple levels.”
According to him, this task is an extraordinary challenge that requires, on the one hand, the close integration of computer-based theory, data analysis, and modeling and, on the other, in vivo and in vitro lab experiments. It was this recognition that led Rajewsky to found BIMSB: “Each stage of gene regulation requires experts in the relevant discipline to work very closely together.”
This concept, which has already been tried and proved successful at the Berlin-Buch Campus, will now be perfected in the “beautiful” new building in Berlin Mitte. “The building’s architecture supports the scientific mission of the institute in the best possible way,” said Rajewsky, adding: “Experimental and theoretical work – wet labs and dry labs – take place directly next to each other. The laboratories therefore have almost no walls. We want to transcend borders, both literally and figuratively.”
The Berlin Institute for Medical Systems Biology (BIMSB) is a key strategic expansion of the scientific profile of Max Delbrück Center for Molecular Medicine (MDC). Nikolaus Rajewsky founded the research unit in 2008 and has headed it ever since. With 16 group leaders and 250 additional researchers, BIMSB represents a great success for the MDC.
It received initial financing of €19 million from the Federal Ministry of Education and Research (BMBF) and the Berlin Senate, as part of the Cutting-Edge Research in the New Federal States initiative. The BMBF currently supports the BIMSB with €17.5 million in annual funding. In addition, BIMSB research groups have so far been awarded grants totaling €38 million.
Collaboration is a pillar of modern research
Without interdisciplinary collaboration it would be impossible to answer the major scientific questions of our time. Even the Nobel Prize winner Professor Christiane Nüsslein-Volhard, former director of the Max Planck Institute for Developmental Biology in Tübingen, is dependent on such collaboration.
She kicked off the Berlin Late Summer Meeting’s series of 16 scientific talks with a lecture on “How fish color their skin: A paradigm for development and evolution of adult patterns.” The researcher asked attendees: “If you know something about this topic, please get in touch with me – I’d like to collaborate with you.” Nüsslein-Volhard is investigating the fishes of the genus Danio. “These patterns are not only beautiful but also useful,” says the researcher. They serve as a form of communication or camouflage.
Only three types of pigment cells create stripes and spots: dark melanophores, yellow xanthophores, and iridescent iridophores. Patterns only emerge, however, if there are interactions between at least two different cell types. “A single cell type is never solely responsible; all three types are necessary for correct patterns,” said Nüsslein-Volhard. The researcher and her team discovered this by selectively mutating genes in silvery-blue striped zebrafish.
The whole spectrum of gene regulation
All the symposium’s talks dealt with gene regulation – whether during the development and differentiation of cells or in the molecular mechanisms of health and disease. BIMSB scientists were involved in many of the research projects presented at the conference.
The scientific questions explored covered a broad range of topics, even down to the atomic level. Patrick Cramer of the Max Planck Institute for Biophysical Chemistry discussed, for example, how RNA polymerase II reads the genes on the DNA strand during the transcription process. When does this RNA-protein machine take a break, and when does it resume its work? Cramer’s answered these questions using highly detailed structural experiments.
The transcription apparatus produces diverse RNA molecules that are later translated mostly into proteins, but only after they have been modified by enzymes, others RNAs, or RNA-protein complexes. Ruth Lehmann of the Skirball Institute of Biomolecular Medicine in New York examined how the molecules organize themselves to an amazing degree, using the example of granules in germline cells.
Edith Heard of the Institut Curie discussed a phenomenon that goes beyond DNA-coded information: Epigenetic processes switch off one of women’s two X chromosomes, but some genes are reactivated – which could play a role in autoimmune diseases.
Amanda Fisher of the MRC Clinical Science Centre in London also presented her discovery that errors in epigenetic signatures can be passed on to offspring.
The researchers have a wide range of experimental methods at their disposal: from molecular biological tools such as CRISPR-Cas to super-resolution microscopes and structural biological techniques to multi-omics approaches. There are also a diverse number of experimental model systems in use, ranging from the single-cell analysis of heterogeneous tumors to organoids to the single-cell characterization of entire animals.
Theoretical models are a fundamental part of systems biology and have been abundantly used in the projects presented – such as the mathematical analysis of chromatin activation described by Leonie Ringrose. Lior Pachter of Caltech in Pasadena outlined strategies for handling the vast amounts of data generated by single-cell analysis.
Single-cell biology was a red thread running through many of the talks. The conference’s final session on Saturday morning was devoted to this rapidly developing technology, which promises to analyze global gene expression in all cells of a tissue or organism – thereby allowing a truly systems biology view of life.
Many BIMSB research groups are already working with single-cell technologies. They are using such technologies to push the boundaries of what’s possible and to develop new areas of research. The new facility in Berlin Mitte will enable the Max Delbrück Center for Molecular Medicine to do just that, by allowing collaborations to be further developed there in the heart of the city’s research hub.
“MDC scientists will soon be pursuing highly collaborative research at two Berlin locations,” Rajewsky said, adding that “the MDC will not split up – there will continue to be only one MDC.”