4 Introduction Glycobiotechnology in Berlin-Brandenburg – The Best Conditions to Yield Sweet Fruit Molecules with sugar components – carbohydrates – are the most abundant biomolecules on Earth. They are ubiquitous in all living organisms and have innumerable functions. Simple carbohydrates are essential for energy metabolism and complex carbohydrates, or glycans, serve as energy storage, build structural component in cells, and are substantially involved in any kind of cellcell interactions. They are, for instance, essential for the interaction between egg and sperm during fertilization. Being a constitutive part of receptors, ion channels, antibodies and antigens, carbohydrates significantly influence physiology, developmental processes and play an important role in disease development and immunology. An impressive example of the impact of glycans can be seen in the heterogeneity of the Influenza A virus. Several subtypes of the flu virus exist and differences in glycosylation patterns can lead to different pathogenicity. Agents causing avian influenza such as H5N1 or H7N9 became a matter of global concern because of its transmission to humans. Impact of carbohydrates in nature • Essential source of energy e.g. glucose, fructose, lactose • Essential energy storage e.g. starch and glycogen • Essential element to build structures e.g. cellulose, lignin, chitin • Essential element for recognition processes e.g. enzymes, receptors, antibodies, glycoproteins, glycolipids Glycoscience (derived from Greek glykòs for sweet) is dedicated to unraveling the complexity of carbohydrates and their functions. After genomics, proteomics, and metabolomics, glycomics has been established as a distinct discipline that focusses on the glycome – the entirety of sugars in living organisms. According to a recent European White Paper on glycobiology, the glycomics R&D market includes enzymes, monoclonal antibodies, instruments, kits and reagents, and is expected to rise to 0 billion by 2019. Berlin-Brandenburg is well positioned to significantly participate in this rapidly growing market. Berlin and Brandenburg recognized the potential of glycosciences early on, and undoubtedly, Werner Reutter, one of the global pioneers exploring this field of science, was a key driver who was consistently committed throughout his life to advancements in glycosciences. From 1979 when he became Head of the Institute of Biochemistry and Molecular Biology at the Freie Universität Berlin until his death in 2016, he infected numerous scientists with his enthusiasm for the exciting field of glycosciences. Political driven activities to enhance this research area in the region reach back to the beginning of the 2000s. Already in 2004, “Berlin-Brandenburg – like very few other regions world-wide – has a network of academic scientific institutions and research-based companies that cover the whole range of glycosciences and glycobiotechnologies: from basic research to applied sciences – from industrial development to applications in medicine and biotechnologies. This competence can give the Berlin-Brandenburg region a leading edge in this highly competitive field of biotechnologies and biomedicine in the international context. New technologies developed in the region like automated synthesis of carbohydrates are now paving avenues for the biomedical application of glycosciences in diagnostics, therapy and preventive medicine. Glyco-engineered biopharmaceuticals and novel diagnostic tools contribute to important advances in the treatment of various diseases in medicine.” Rudolf Tauber Charité – Universitätsmedizin Berlin, Head Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry
Introduction 5 BioTOP introduced the glycobiotechnology assets of the region in a special issue of its BioTOPics publication. In the same year an “Innovation Forum Glycans” was initiated. Many other congresses, workshops and events followed and continue up to the present – including seven “Glycan Forums” and the “Treffpunkt Bioinfomatik und Glykobiotechnologie”. The strong local commitment was also demonstrated by the establishment of the glycobiotechnolgy network “Glykostrukturfabrik” (Glycostructure Facility). The goal of this platform, which existed from 2005 to 2008, was to combine excellence in basic glycobiological research and the development of related products and services, while building a glycobiological center of excellence in the Berlin-Brandenburg region. The ongoing strong political commitment is also reflected in the joint innovation strategy of Berlin and Brandenburg (Masterplan Gesundheitsregion Berlin-Brandenburg). It incorporates future support for the development of glycobiology as an enabling technology for the biotech sector. One more recent result of regional activities was the establishment of the glyconet Berlin-Brandenburg in 2016. The network supports research and development in glycobiotechnology, synthetic chemistry, analytical sciences and medical chemistry. The main goal is to strengthen and visualize regional skills and education in these areas of the life sciences. Soon after its kick-off in December 2016 glyconet BB set up a “Winter School” for junior scientists to provide insights on the theory and practice of glycosciences. Glyconet BB is also organizing its first international congress in September 2017. The congress on “New and Emerging Technologies” will provide a platform for international scientific exchange and showcase the newest developments in glycobiotechnology, biochemistry, molecular biology, biofunctional materials, antibody technologies, synthetic biology and related areas. The capital region is also attractive for other event organizers active in the glycosciences field. In early 2017, Berlin was the venue of the first “GlycoBioTec”, an international symposium hosted by the Max Planck institute of Complex Technical Systems Magdeburg. Since October 2009, Berlin and Potsdam have been venues for five international “Beilstein Glyco-Bioinformatics Symposia”, organized by the Frankfurt-based foundation Beilstein Institut, and with Peter Seeberger, Director of the Max Planck Institute of Colloids and Interfaces as member of the scientific committee. Potential of carbohydrates in man-made applications • Novel diagnostics • Novel drugs • Optimized drugs • Novel vaccines • New methods of drug delivery • Novel biomaterials • Food optimization • Applications for agriculture The key players which make the Berlin-Brandenburg region one of the leading centers of glycosciences and glycobiotechnology in Europe are the universities, the research institutes and last but not least an increasing number of companies. About 50 players in science and industry are committed to exploring the secrets of carbohydrates and focusing their research activities on the development of new approaches and applications which lead to improvements in healthcare. Key players in the academic environment are the Max-Planck-Institute for Colloids and Interfaces with Peter Seeberger as a globally renowned pioneer of glycosciences, and the Charité – Universitätsmedizin Berlin (Véronique Blanchard and Rudolf Tauber working group). Among other institutions the Beuth University of Applied Sciences Berlin (Stephan Hinderlich working group), Fraunhofer Institute for Cell Therapy and Immunology (Stefan Kubick working group) as well as the Fraunhofer Institute for Applied Polymer Research (Alexander Böker working group) are strongly engaged in glycosciences. Major industry actors include Glycotope GmbH and ProBioGen AG in the glycoengineering area, GlycoUniverse GmbH & CO KGaA, providing automated carbohydrates synthesizers, and Scienion AG, active in the development of glycan-based microarrays. These and other players use their distinct glycosciences expertise – often in collaborative efforts – for comprehensive glycoanalytics and to develop novel diagnostics and therapeutic agents, biosimilars and biobetters, new vaccines and innovative materials. Examples will be presented on the following pages. Pioneering sugar technologies for centuries Berlin has been a pioneer of sugar technologies for more than 200 years. The chemist Andreas Sigismund Marggraf (1709 –1782) discovered the high sugar content of beets and laid the foundation for the industrial process for extracting sugar from sugar beet – a breakthrough, since this technology allowed producers to achieve independence from expensive cane sugar.